1
00:00:05,400 --> 00:00:06,920
I'M DAN ROTROSEN, DIRECTOR

2
00:00:06,920 --> 00:00:09,960
DIVISION OF ALLERGY IMMUNOLOGY

3
00:00:09,960 --> 00:00:11,640
TRANSPLANTATION AT NIAID.

4
00:00:11,640 --> 00:00:13,640
PLEASURE TO WELCOME Y'ALL TOLL

5
00:00:13,640 --> 00:00:18,440
THE OPEN SESSION OF OUR ADVISORY

6
00:00:18,440 --> 00:00:19,080
COUNCIL COMMITTEE.

7
00:00:19,080 --> 00:00:24,240
WE HAVE AN UNUSUAL SET OF TALKS

8
00:00:24,240 --> 00:00:24,800
THIS AFTERNOON.

9
00:00:24,800 --> 00:00:28,400
WE ARE GOING TO BE FOCUSING ON

10
00:00:28,400 --> 00:00:31,320
INDUCTION AND MAINTENANCE

11
00:00:31,320 --> 00:00:35,440
DURABILITY OF IMMUNE RESPONSES

12
00:00:35,440 --> 00:00:40,840
TO COVID INFECTION ITSELF SAND

13
00:00:40,840 --> 00:00:43,040
SARS COV-2 VACCINES WITH A GROUP

14
00:00:43,040 --> 00:00:46,960
OF SPEAKERS WHO ARE JUST

15
00:00:46,960 --> 00:00:48,240
PIONEERS AND LEADERS IN THIS

16
00:00:48,240 --> 00:00:51,240
FIELD SO WE ARE VERY HAPPY TO

17
00:00:51,240 --> 00:00:55,440
HAVE THE TIMELY OPPORTUNITY TO

18
00:00:55,440 --> 00:00:59,440
COVER THIS.

19
00:00:59,440 --> 00:01:01,960
ALISON DECKHUT AUGUSTINE WILL

20
00:01:01,960 --> 00:01:03,400
GIVE A BRIEF OVERVIEW OF THE

21
00:01:03,400 --> 00:01:04,640
PROGRAMS UNDER WHICH SOME OF

22
00:01:04,640 --> 00:01:05,400
THESE INVESTIGATORS HAVE BEEN

23
00:01:05,400 --> 00:01:07,480
WORKING.

24
00:01:07,480 --> 00:01:12,200
AND ALISON, IF YOU CAN GET YOUR

25
00:01:12,200 --> 00:01:14,640
SLIDES UP AND SHARE THOSE, THAT

26
00:01:14,640 --> 00:01:15,400
COULD BE GREAT.

27
00:01:15,400 --> 00:01:16,840
WHILE YOU ARE DOING THAT I WILL

28
00:01:16,840 --> 00:01:22,040
MENTION AT THE END OF THE PANEL

29
00:01:22,040 --> 00:01:24,240
DISCUSSION WE HAVE ONE CONCEPT

30
00:01:24,240 --> 00:01:26,800
CLEARANCE FOR PRESENTATION AND

31
00:01:26,800 --> 00:01:28,040
DISCUSSION BY COUNCIL MEMBERS WE

32
00:01:28,040 --> 00:01:30,880
DON'T WANT TO SHORTCHANGE THAT

33
00:01:30,880 --> 00:01:33,840
BUT WE DO HOPE THERE WILL BE

34
00:01:33,840 --> 00:01:37,040
THOUGHTS BACK AND FORTH ON THE

35
00:01:37,040 --> 00:01:40,560
MAJOR TOPIC OF THE AFTERNOON.

36
00:01:40,560 --> 00:01:43,240
KNOWING WE ARE VERY TIGHT ON

37
00:01:43,240 --> 00:01:44,880
TIME WE HAVE UNUSUALLY LARGE

38
00:01:44,880 --> 00:01:46,840
NUMBER OF SPEAKERS TODAY, I'M

39
00:01:46,840 --> 00:01:52,960
GOING TO LIMIT MY DIRECTOR

40
00:01:52,960 --> 00:01:54,080
OVERVIEW COMMENTS TO WHAT I

41
00:01:54,080 --> 00:01:55,000
COVERED.

42
00:01:55,000 --> 00:01:56,120
ALISON, PLEASE GO AHEAD.

43
00:01:56,120 --> 00:01:57,960
>> THANK YOU, CAN EVERYONE SEE

44
00:01:57,960 --> 00:01:58,600
MY SLIDES?

45
00:01:58,600 --> 00:01:59,440
>> YES.

46
00:01:59,440 --> 00:02:00,200
>> GREAT.

47
00:02:00,200 --> 00:02:02,680
SO MY NAME IS ALISON DECKHUT

48
00:02:02,680 --> 00:02:05,240
AUGUSTINE, I'M THE CHIEF OF THE

49
00:02:05,240 --> 00:02:06,720
BASIC IMMUNOLOGY BRANCH AND I

50
00:02:06,720 --> 00:02:08,040
WOULD LIKE TO THANK EVERYONE FOR

51
00:02:08,040 --> 00:02:09,960
JOINING THIS OPEN SESSION AND

52
00:02:09,960 --> 00:02:13,640
ESPECIALLY TO OUR SPEAKERS AND

53
00:02:13,640 --> 00:02:15,440
MODERATORS FOR AGREEING TO DO

54
00:02:15,440 --> 00:02:18,640
THIS WORKSHOP WITH US.

55
00:02:18,640 --> 00:02:22,200
SO AS DR. PACHY MENTIONED TODAY

56
00:02:22,200 --> 00:02:24,400
THE COVID-19 INCIDENCE GLOBALLY

57
00:02:24,400 --> 00:02:26,760
HAS REACHED OVER 358 MILLION

58
00:02:26,760 --> 00:02:28,440
PEOPLE WITH 72 MILLION OF THOSE

59
00:02:28,440 --> 00:02:31,680
PEOPLE INFECTED IN THE US.  IT

60
00:02:31,680 --> 00:02:34,760
HAS ALSO LED TO OVER 5.6 MYTH

61
00:02:34,760 --> 00:02:36,240
DEATHS GLOBALLY AND ALMOST A

62
00:02:36,240 --> 00:02:39,440
MILLION IN THE US.  FORTUNATELY

63
00:02:39,440 --> 00:02:42,560
ALSO AS DR. FAUCI MENTIONED

64
00:02:42,560 --> 00:02:44,120
VACCINE DEVELOPMENT FOR SARS

65
00:02:44,120 --> 00:02:45,760
COV-2 HAS BEEN UNPRECEDENT AND

66
00:02:45,760 --> 00:02:48,280
WE DO HAVE A NUMBER OF VACCINES

67
00:02:48,280 --> 00:02:50,600
THAT ARE BEING USED AROUND THE

68
00:02:50,600 --> 00:02:50,960
GLOBE.

69
00:02:50,960 --> 00:02:54,960
IN THE U.S. WE HAVE HAD OVER 210

70
00:02:54,960 --> 00:02:56,080
MILLION PEOPLE WHO WERE FULLY

71
00:02:56,080 --> 00:02:58,320
VACCINATED AND YOU CAN SEE THE

72
00:02:58,320 --> 00:03:00,280
BREAK DOWN OF THE AGE GROUPS

73
00:03:00,280 --> 00:03:02,240
HERE, WON'T GO INTO THAT.

74
00:03:02,240 --> 00:03:06,440
AND THEN WE ALSO HAVE 84-POINT

75
00:03:06,440 --> 00:03:08,080
-- 8 MILLION PEOPLE WHO RECEIVED

76
00:03:08,080 --> 00:03:09,440
A BOOSTER DOSE.

77
00:03:09,440 --> 00:03:11,840
AND THEN MY NEXT SLIDE YOU WILL

78
00:03:11,840 --> 00:03:13,640
SEE WHY THAT IS IMPORTANT.

79
00:03:13,640 --> 00:03:16,480
IF WE LOOK AT COVID CASES AND

80
00:03:16,480 --> 00:03:18,080
DEATH BY VACCINATION STATUS YOU

81
00:03:18,080 --> 00:03:24,200
CAN SEE ON THE TOP PANEL ON THE

82
00:03:24,200 --> 00:03:25,840
RIGHT THAT VACCINE WAS

83
00:03:25,840 --> 00:03:27,440
PROTECTING PEOPLE VERY WELL EVEN

84
00:03:27,440 --> 00:03:29,600
FROM INFECTION BUT WE HAVE HAD

85
00:03:29,600 --> 00:03:31,040
INCREASES IN BREAK THROUGH

86
00:03:31,040 --> 00:03:32,440
INFECTIONS DUE TO OMICRON AND

87
00:03:32,440 --> 00:03:33,800
PROBABLY CHANGES IN IMMUNITY

88
00:03:33,800 --> 00:03:36,440
THAT HOPEFULLY YOU WILL HEAR

89
00:03:36,440 --> 00:03:37,640
ABOUT TODAY BUT STILL BETTER

90
00:03:37,640 --> 00:03:39,600
THAN THE UNVACCINATED.

91
00:03:39,600 --> 00:03:41,680
VACCINE AND BOOSTERS ARE FOR

92
00:03:41,680 --> 00:03:43,600
SURE PROTECTING PEOPLE STILL

93
00:03:43,600 --> 00:03:47,080
AGAINST HOSPITALIZATION AND

94
00:03:47,080 --> 00:03:47,280
DEATH.

95
00:03:47,280 --> 00:03:49,720
SO THAT'S STILL GOOD NEWS FOR

96
00:03:49,720 --> 00:03:49,920
THIS.

97
00:03:49,920 --> 00:03:51,200
HOWEVER THERE IS STILL A LOT OF

98
00:03:51,200 --> 00:03:53,160
QUESTIONS THAT REMAIN REGARDING

99
00:03:53,160 --> 00:03:54,400
THE BREADTH AND DURABILITY OF

100
00:03:54,400 --> 00:03:55,400
IMMUNE PROTECTION THAT IS

101
00:03:55,400 --> 00:03:58,360
INDUCED BY VACCINATION AND

102
00:03:58,360 --> 00:03:59,800
NATURAL INFECTION.

103
00:03:59,800 --> 00:04:01,720
NIAID AND DAIT IN PARTICULAR

104
00:04:01,720 --> 00:04:03,840
HAVE BEEN ABLE TO SUPPORT OOH A

105
00:04:03,840 --> 00:04:06,640
NUMBER OF OUR INVESTIGATORS TO

106
00:04:06,640 --> 00:04:08,680
UNDERSTAND HOW THE IMMUNE

107
00:04:08,680 --> 00:04:12,080
RESPONSE IS TRIGGERED BY NATURAL

108
00:04:12,080 --> 00:04:14,160
INFECTION AND/OR VACCINATION AND

109
00:04:14,160 --> 00:04:16,080
HOW THAT AFFECTS FUNCTION AND

110
00:04:16,080 --> 00:04:18,320
DURABILITY OF THE ADAPTIVE

111
00:04:18,320 --> 00:04:20,440
IMMUNE RESPONSE SO IN ORDER TO

112
00:04:20,440 --> 00:04:21,840
GIVE EVERYONE A BRIEF OVERVIEW

113
00:04:21,840 --> 00:04:24,320
OF WHAT IS GOING ON IN THESE

114
00:04:24,320 --> 00:04:25,560
FIELDS, WE HAVE GATHERED SOME OF

115
00:04:25,560 --> 00:04:29,440
THE LEADERS IN THE FIELD WHO

116
00:04:29,440 --> 00:04:31,640
WILL GIVE US THEIR RECENT

117
00:04:31,640 --> 00:04:33,840
UPDATES ON THEIR RESEARCH AS

118
00:04:33,840 --> 00:04:35,040
WELL AS GIVE A LITTLE BROADER

119
00:04:35,040 --> 00:04:36,840
OVERVIEW WHAT IS GOING ON IN THE

120
00:04:36,840 --> 00:04:37,240
FIELD.

121
00:04:37,240 --> 00:04:38,680
AND THOSE WILL BE OUR PANEL

122
00:04:38,680 --> 00:04:39,480
SPEAKERS.

123
00:04:39,480 --> 00:04:41,040
WE HAVE EIGHT PANEL SPEAKERS

124
00:04:41,040 --> 00:04:43,160
THAT WILL TALK FOR 20 MINUTES OR

125
00:04:43,160 --> 00:04:44,640
SO AND I THIS MAYBE A LITTLE BIT

126
00:04:44,640 --> 00:04:47,080
OF TIME FOR QUESTION AFTER THAT.

127
00:04:47,080 --> 00:04:48,360
DEPENDING HOW WE ARE DOING ON

128
00:04:48,360 --> 00:04:48,560
TIME.

129
00:04:48,560 --> 00:04:50,480
THEN WE'LL HAVE A PANEL

130
00:04:50,480 --> 00:04:52,040
DISCUSSION THAT WILL FOCUS ON

131
00:04:52,040 --> 00:04:55,080
NEW APPROACH TOOLS AND

132
00:04:55,080 --> 00:04:57,120
TECHNOLOGIES THAT HAVE OR THAT

133
00:04:57,120 --> 00:04:58,440
ARE NEEDED TO EXPAND OUR

134
00:04:58,440 --> 00:05:00,000
KNOWLEDGE TO REALLY UNDERSTAND

135
00:05:00,000 --> 00:05:03,200
THE ADAPTIVE RESPONSE TO THIS

136
00:05:03,200 --> 00:05:03,640
INFECTION.

137
00:05:03,640 --> 00:05:06,840
OUR MODERATORS FOR THIS PANEL

138
00:05:06,840 --> 00:05:08,600
DISCUSSION AND FOR THE WORKSHOP

139
00:05:08,600 --> 00:05:11,120
IN GENERAL ARE DR.S DONNA FARBER

140
00:05:11,120 --> 00:05:13,040
AND RAFI AHMED.

141
00:05:13,040 --> 00:05:14,920
AND WITH THAT, ACTUALLY THAT'S

142
00:05:14,920 --> 00:05:17,440
ALL I WAS GOING TO SAY.

143
00:05:17,440 --> 00:05:19,640
AND I WOULD LIKE TO TURN IT OVER

144
00:05:19,640 --> 00:05:22,080
TO RAFI IN THE INTEREST OF TIME

145
00:05:22,080 --> 00:05:23,320
AND I DON'T KNOW IF DONNA HAS

146
00:05:23,320 --> 00:05:24,640
BEEN ABLE TO JOIN YET.

147
00:05:24,640 --> 00:05:25,280
>> I'M HERE.

148
00:05:25,280 --> 00:05:30,240
>> PERFECT.

149
00:05:30,240 --> 00:05:32,280
(OVERLAPPING SPEAKERS)

150
00:05:32,280 --> 00:05:36,520
>> ALISON ONE CLARIFICATION.

151
00:05:36,520 --> 00:05:38,440
IF THE INDIVIDUAL TIME SLOTS 15

152
00:05:38,440 --> 00:05:39,640
OR 20 MINUTES?

153
00:05:39,640 --> 00:05:40,040
>> 15.

154
00:05:40,040 --> 00:05:42,640
WHATEVER I TOLD YOU GUYS BEFORE.

155
00:05:42,640 --> 00:05:44,240
I APOLOGIZE.

156
00:05:44,240 --> 00:05:46,680
YOU DIDN'T GET FIVE MINUTE

157
00:05:46,680 --> 00:05:46,880
BEAKS.

158
00:05:46,880 --> 00:05:49,320
>> JUST REMINDER TO ALL THE

159
00:05:49,320 --> 00:05:50,040
SPEAKERS TOTAL TIME IS 15

160
00:05:50,040 --> 00:05:51,440
MINUTES.

161
00:05:51,440 --> 00:05:53,840
IF YOU USE UP THE 15 MINUTES

162
00:05:53,840 --> 00:05:55,320
THEN THERE'S NO QUESTIONS AFTER

163
00:05:55,320 --> 00:05:55,840
YOUR TALK.

164
00:05:55,840 --> 00:06:00,240
BUT AGAIN NO ONE SHOULD EXCEED

165
00:06:00,240 --> 00:06:00,960
15.

166
00:06:00,960 --> 00:06:02,640
DONNA, YOU WANT TO INTRODUCE THE

167
00:06:02,640 --> 00:06:03,960
FIRST FOUR SPEAKERS AND I DO THE

168
00:06:03,960 --> 00:06:05,760
NEXT FOUR OR DO YOU WANT TO DO

169
00:06:05,760 --> 00:06:06,600
THE WHOLE THING?

170
00:06:06,600 --> 00:06:07,040
(OVERLAPPING SPEAKERS)

171
00:06:07,040 --> 00:06:09,640
>> I CAN'T TURN MY VIDEO ON.

172
00:06:09,640 --> 00:06:11,440
WON'T LET ME TURN MY VIDEO ON.

173
00:06:11,440 --> 00:06:16,080
BUT I AM HERE.

174
00:06:16,080 --> 00:06:17,400
GO AHEAD PLEASE.

175
00:06:17,400 --> 00:06:19,720
>> GREAT.

176
00:06:19,720 --> 00:06:21,440
SO IT IS A PLEASURE TO INTRODUCE

177
00:06:21,440 --> 00:06:23,680
AS THE FIRST SPEAKER SHANE

178
00:06:23,680 --> 00:06:27,040
CROTTI FROM THE LA HOLLA

179
00:06:27,040 --> 00:06:29,720
INSTITUTE TALKING DURABILITY OF

180
00:06:29,720 --> 00:06:31,640
ANTIBODY AND T-CELL RESPONSES TO

181
00:06:31,640 --> 00:06:36,440
SARS COV-2 VACCINATION.

182
00:06:36,440 --> 00:06:37,040
>> GREAT.  THANKS.

183
00:06:37,040 --> 00:06:41,360
IS THE SLIDE UP?

184
00:06:41,360 --> 00:06:42,200
>> WE CAN SEE IT

185
00:06:42,200 --> 00:06:46,200
>> THIS SHOULD BE A FANTASTIC

186
00:06:46,200 --> 00:06:46,600
SESSION.

187
00:06:46,600 --> 00:06:50,000
SO I'LL AT LJI.

188
00:06:50,000 --> 00:06:52,560
OBVIOUSLY THE COVID-19 PANDEMIC

189
00:06:52,560 --> 00:06:55,840
HAS CHANGED ALL OUR LIVES IN

190
00:06:55,840 --> 00:06:59,080
MANY WAYS AND I THINK THIS HITS

191
00:06:59,080 --> 00:07:01,040
HOME PRETTY QUICKLY.

192
00:07:01,040 --> 00:07:03,600
SO WE PARTICULARLY IN

193
00:07:03,600 --> 00:07:06,360
COLLABORATION WITH ALEX AT OJI

194
00:07:06,360 --> 00:07:08,000
EARLY IN THE PANDEMIC TRYING TO

195
00:07:08,000 --> 00:07:09,240
UNDERSTAND IMMUNE RESPONSES TO

196
00:07:09,240 --> 00:07:12,240
THIS INFECTION AND WE HAD THE

197
00:07:12,240 --> 00:07:14,720
FIRST STUDY LOOKING AT VIRUS

198
00:07:14,720 --> 00:07:17,440
SPECIFIC CD4 T-CELLS, CD8

199
00:07:17,440 --> 00:07:19,120
T-CELLS AND ANTIBODY RESPONSES

200
00:07:19,120 --> 00:07:21,480
IN PEOPLE WITH ACUTE INFECTIONS.

201
00:07:21,480 --> 00:07:25,440
AND THE REASON WE DID THAT IS

202
00:07:25,440 --> 00:07:27,480
BECAUSE YOUR ADAPTIVE IMMUNE

203
00:07:27,480 --> 00:07:30,240
SYSTEM REALLY PREDOMINANTLY

204
00:07:30,240 --> 00:07:32,240
CONSISTS OF THREE MAYOR BRANCHES

205
00:07:32,240 --> 00:07:34,160
YOUR ANTIBODY RESPONSES COME

206
00:07:34,160 --> 00:07:36,240
FROM B CELLS AND TWO KINDS OF

207
00:07:36,240 --> 00:07:38,920
T-CELLS, CD4 T-CELLS AN CD8

208
00:07:38,920 --> 00:07:39,720
T-CELLS THAT HAVE DIFFERENT

209
00:07:39,720 --> 00:07:40,240
JOBS.

210
00:07:40,240 --> 00:07:42,400
I'M GOING TO COVER A LITTLE BIT

211
00:07:42,400 --> 00:07:45,000
OF CONTEXT TO HOPEFULLY

212
00:07:45,000 --> 00:07:46,160
FACILITATE THE OTHER FANTASTIC

213
00:07:46,160 --> 00:07:47,680
EXPERTS IN THIS SESSION GOING

214
00:07:47,680 --> 00:07:53,160
INTO DEPTH ON MORE OF THESE.

215
00:07:53,160 --> 00:07:54,960
AND YOUR IMMUNE SYSTEM HAS THESE

216
00:07:54,960 --> 00:07:56,920
THREE MAJOR BRANCHES FOR A

217
00:07:56,920 --> 00:07:57,320
REASON.

218
00:07:57,320 --> 00:07:58,880
EACH OF THESE HAVE DIFFERENT

219
00:07:58,880 --> 00:08:00,040
WEAPONS THAT ARE GOOD IN

220
00:08:00,040 --> 00:08:02,400
DIFFERENT SCENARIOS GOOD AGAINST

221
00:08:02,400 --> 00:08:07,160
DIFFERENT DISEASES AND I

222
00:08:07,160 --> 00:08:08,960
GENERALLY SAY IT IS LIKE THE

223
00:08:08,960 --> 00:08:09,440
MILITARY.

224
00:08:09,440 --> 00:08:11,400
YOU HAVE MULTIPLE BRANCHES OF

225
00:08:11,400 --> 00:08:12,680
THE MILITARY THEY EACH HAVE

226
00:08:12,680 --> 00:08:15,800
DIFFERENT KINDS OF WEAPONS THAT

227
00:08:15,800 --> 00:08:17,360
TEND TO BE BETTER IN ASSORTMENT

228
00:08:17,360 --> 00:08:18,080
OF SOME ENVIRONMENTS THANS

229
00:08:18,080 --> 00:08:20,280
OTHERS AND COLLABORATE WELL IN

230
00:08:20,280 --> 00:08:21,640
CERTAIN DISEASES TO TRYING TO

231
00:08:21,640 --> 00:08:22,640
UNDERSTAND HOW MUCH THAT HAPPENS

232
00:08:22,640 --> 00:08:25,200
IN THE CONTEXT OF SARS COV-2.

233
00:08:25,200 --> 00:08:26,800
OTHER SPEAKERS TODAY ARE GOING

234
00:08:26,800 --> 00:08:30,520
TO TALK MORE SPECIFICALLY ABOUT

235
00:08:30,520 --> 00:08:32,440
INFECTION IN COVID-19 DISEASE

236
00:08:32,440 --> 00:08:33,840
AND I WILL TALK IMMUNE RESPONSES

237
00:08:33,840 --> 00:08:39,440
AND MEMORY IN THE CONTEXT OF

238
00:08:39,440 --> 00:08:40,160
VACCINES.

239
00:08:40,160 --> 00:08:43,440
A PRIMARY PAPER FROM US ON THIS

240
00:08:43,440 --> 00:08:45,440
CAME OUT A FEW MONTHS AGO

241
00:08:45,440 --> 00:08:46,680
RELATED TO RNA VACCINES AND HERE

242
00:08:46,680 --> 00:08:47,960
IS A SUMMARY HERE.

243
00:08:47,960 --> 00:08:51,000
THE RNA VACCINES HAVE DONE

244
00:08:51,000 --> 00:08:53,040
INCREDIBLY WELL PROVIDING AT

245
00:08:53,040 --> 00:08:54,280
LEAST SHORT TERM PROTECTIVE

246
00:08:54,280 --> 00:08:57,160
IMMUNITY TO PEOPLE AND THEY

247
00:08:57,160 --> 00:08:59,960
CLEARLY ELICIT REALLY STRONG

248
00:08:59,960 --> 00:09:01,840
EARLY NEUTRALIZING ANTIBODY

249
00:09:01,840 --> 00:09:04,360
RESPONSES AND ONE OF THE BIG

250
00:09:04,360 --> 00:09:06,440
OPEN QUESTIONS WAS HOW GOOD ARE

251
00:09:06,440 --> 00:09:08,160
THESE VACCINES AT GENERATING

252
00:09:08,160 --> 00:09:09,040
MEMORY.

253
00:09:09,040 --> 00:09:10,760
NOT ONLY PROTECTION FOR A FEW

254
00:09:10,760 --> 00:09:14,440
MONTHS BUT MEMORY FOR ONE, TWO,

255
00:09:14,440 --> 00:09:15,760
FIVE, TEN YEARS WOULD DEPEND ON

256
00:09:15,760 --> 00:09:18,240
GENERATION OF IMMUNE MEMORY.

257
00:09:18,240 --> 00:09:20,040
SO WHAT WE DID WAS TO MEASURE

258
00:09:20,040 --> 00:09:21,640
PARTICULARLY T-CELL MEMORY WHICH

259
00:09:21,640 --> 00:09:24,040
HADN'T BEEN PREVIOUSLY MEASURED

260
00:09:24,040 --> 00:09:26,080
IN TO AN RNA VACCINE BEFORE AND

261
00:09:26,080 --> 00:09:27,240
SEE HOW WELL THESE RNA VACCINES

262
00:09:27,240 --> 00:09:27,680
DO THIS.

263
00:09:27,680 --> 00:09:29,520
WE DID THIS PARTICULARLY IN THE

264
00:09:29,520 --> 00:09:32,840
CONTEXT OF A LOW DOSE MODERNA

265
00:09:32,840 --> 00:09:33,560
VACCINE ESSENTIALLY SIMILAR TO

266
00:09:33,560 --> 00:09:35,520
DOSE OF PFIZER VACCINE AND WHAT

267
00:09:35,520 --> 00:09:37,240
WE OBSERVED IN PEOPLE WHO

268
00:09:37,240 --> 00:09:38,640
RECEIVED TWO DOSES OF THOSE

269
00:09:38,640 --> 00:09:40,080
VACCINES WAS THAT SIX MONTHS

270
00:09:40,080 --> 00:09:42,280
AFTER THE SECOND DOSE, TWO DOSE

271
00:09:42,280 --> 00:09:43,440
REGIMENT OF THE VACCINE, THERE

272
00:09:43,440 --> 00:09:45,640
WAS A TENFOLD DROP IN ANTIBODY,

273
00:09:45,640 --> 00:09:48,040
THIS IS REPORTED BY OTHERS OUT

274
00:09:48,040 --> 00:09:50,600
AT SIX MONTHS BUT THE T-CELLS

275
00:09:50,600 --> 00:09:52,640
HAD ABOUT THE VIRUS SPECIFIC

276
00:09:52,640 --> 00:09:55,400
T-CELLS HAD A TWOFOLD DECREASE

277
00:09:55,400 --> 00:09:57,840
CD4 AND CD8 T-CELLS HAD TWOFOLD

278
00:09:57,840 --> 00:10:00,040
DECREASE FROM PEAK LEVELS, OUT

279
00:10:00,040 --> 00:10:02,600
TO SIX MONTHS AND AFTER THE

280
00:10:02,600 --> 00:10:03,960
SECOND IMMUNIZATION.

281
00:10:03,960 --> 00:10:06,280
WE THINK THAT IS QUITE GOOD AND

282
00:10:06,280 --> 00:10:07,240
IMPRESSIVE FOR THESE VACCINES

283
00:10:07,240 --> 00:10:08,640
BECAUSE WE WOULD EXPECT THAT

284
00:10:08,640 --> 00:10:10,960
THIS WOULD BE THE PERIOD OF THE

285
00:10:10,960 --> 00:10:13,480
LARGEST DECLINE AND IT YOUR MORE

286
00:10:13,480 --> 00:10:15,240
LIKELY TO BE MORE STABLE LATER

287
00:10:15,240 --> 00:10:16,640
ON SO IT WOULDN'T BE SURPRISING

288
00:10:16,640 --> 00:10:22,560
IF PEOPLE HAD CD4 AND CD8

289
00:10:22,560 --> 00:10:24,960
T-CELLS MULTIPLE YEARS POST

290
00:10:24,960 --> 00:10:26,040
VACCINATION BASED ON THE DATA.

291
00:10:26,040 --> 00:10:27,400
WE COMPARED TO IMMUNITY

292
00:10:27,400 --> 00:10:30,240
GENERATED BY PREVIOUS INFECTION

293
00:10:30,240 --> 00:10:32,640
AND THEN ACTUALLY THE CD4 AND

294
00:10:32,640 --> 00:10:35,280
CD8 T-CELL MEMORY TO SPIKE WAS

295
00:10:35,280 --> 00:10:37,840
ACTUALLY ESSENTIALLY EQUIVALENT

296
00:10:37,840 --> 00:10:39,560
BETWEEN PREVIOUS INFECTION AND

297
00:10:39,560 --> 00:10:41,040
VACCINATION AT SIX MONTHS LATER

298
00:10:41,040 --> 00:10:42,960
WHICH AGAIN WE CONSIDER PRETTY

299
00:10:42,960 --> 00:10:45,640
IMPRESSIVE FOR TWO DOSES OF LOW

300
00:10:45,640 --> 00:10:46,480
DOSE RNA VACCINE.

301
00:10:46,480 --> 00:10:49,760
AND LASTLY, AGE IS CERTAINLY A

302
00:10:49,760 --> 00:10:52,360
BIG FACTOR FOR COVID-19, THE

303
00:10:52,360 --> 00:10:54,080
BIGGEST RISK FACTOR FOR

304
00:10:54,080 --> 00:10:56,320
HOSPITALIZATION AND DEATH SO HOW

305
00:10:56,320 --> 00:10:57,840
ARE THESE VACCINES WORKING IN

306
00:10:57,840 --> 00:10:58,520
OLDER INDIVIDUALS?

307
00:10:58,520 --> 00:11:00,640
THIS CLINICAL TRIAL HAD PEOPLE

308
00:11:00,640 --> 00:11:03,520
RUN PEOPLE WHO ARE 55 AND OLDER

309
00:11:03,520 --> 00:11:06,720
OR 70 AND OLDER AND IN VARY VERY

310
00:11:06,720 --> 00:11:08,360
ENCOURAGINGLY THE T-CELL MEMORY

311
00:11:08,360 --> 00:11:10,000
GENERATED IN THE OLDER GROUPS

312
00:11:10,000 --> 00:11:11,920
WAS EQUIVALENT TO THAT OF

313
00:11:11,920 --> 00:11:13,640
YOUNGER ADULTS.

314
00:11:13,640 --> 00:11:15,000
I WON'T TALK ABOUT THIS TODAY

315
00:11:15,000 --> 00:11:16,800
BUT A KEY REASON WE RAN THIS

316
00:11:16,800 --> 00:11:20,440
STUDY WAS TO LOOK FOR BIOLOGICAL

317
00:11:20,440 --> 00:11:22,000
IMPACT OF CROSS REACTIVE MEMORY

318
00:11:22,000 --> 00:11:23,680
T-CELLS AND WE DID SEE THAT.

319
00:11:23,680 --> 00:11:27,080
IN A SEPARATE STUDY LED BY JOHN

320
00:11:27,080 --> 00:11:28,800
WEARY AND COLLEAGUES I'M

321
00:11:28,800 --> 00:11:30,000
SUMMARIZING DATA NOT ONLY FROM

322
00:11:30,000 --> 00:11:31,920
OUR LAB BUT OTHER LAB TEAMS,

323
00:11:31,920 --> 00:11:33,280
THEY SHOWED MEMORY B CELLS WERE

324
00:11:33,280 --> 00:11:35,600
ALSO GENERATED QUITE WELL BY TWO

325
00:11:35,600 --> 00:11:37,320
DOSES O VACCINE AND

326
00:11:37,320 --> 00:11:39,480
PRE-COMPARABLE TO THAT OF

327
00:11:39,480 --> 00:11:41,040
INFECTED INDIVIDUALS WHICH WE

328
00:11:41,040 --> 00:11:42,760
AND RAFI AND OTHERS HAVE SHOWN

329
00:11:42,760 --> 00:11:43,680
PREVIOUSLY.

330
00:11:43,680 --> 00:11:45,920
SO YOU HAVE GOT MEMORY CD4

331
00:11:45,920 --> 00:11:49,000
T-CELLS, MEMORY CD8 T-CELLS AND

332
00:11:49,000 --> 00:11:50,920
MEMORY B CELLS GENERATE AND

333
00:11:50,920 --> 00:11:53,840
ACUTE ANTIBODY RESPONSES BEING

334
00:11:53,840 --> 00:11:55,600
GENERATED WAIT WELL BY TWO DOSE

335
00:11:55,600 --> 00:12:00,680
RNA VACCINATION.

336
00:12:00,680 --> 00:12:04,320
SO THEN WHY AREN'T THE VACCINES

337
00:12:04,320 --> 00:12:06,320
PROTECTING PERFECTEDLY AGAINST

338
00:12:06,320 --> 00:12:06,600
VARIANTS?

339
00:12:06,600 --> 00:12:07,080
OVER TIME?

340
00:12:07,080 --> 00:12:09,360
AND SO I'M GOING TO INTRODUCE

341
00:12:09,360 --> 00:12:10,600
THOSE CONCEPTS HERE.

342
00:12:10,600 --> 00:12:12,480
AND SOME OF THE NEWEST DATA ON

343
00:12:12,480 --> 00:12:15,240
THIS, AS IT RELATES TO VACCINE

344
00:12:15,240 --> 00:12:16,280
IMMUNITY AND LONGEVITY.

345
00:12:16,280 --> 00:12:18,720
I LOVE THIS ARTICLE IN

346
00:12:18,720 --> 00:12:21,160
SCIENTIFIC AMERICAN THAT REALLY

347
00:12:21,160 --> 00:12:23,560
HIGHLIGHTS YOUR IMMUNE SYSTEM IS

348
00:12:23,560 --> 00:12:25,440
EVOLVED MULTIPLE POWERFUL

349
00:12:25,440 --> 00:12:29,000
MECHANISMS TO FIGHT VIRAL

350
00:12:29,000 --> 00:12:29,440
VARIANTS.

351
00:12:29,440 --> 00:12:30,640
I SHOW THE ARTICLE BECAUSE IT

352
00:12:30,640 --> 00:12:31,800
SHOW IT IS VIRUS EXPLODING AND

353
00:12:31,800 --> 00:12:33,640
THAT IS ALWAYS A GOOD SIGN.

354
00:12:33,640 --> 00:12:35,920
AND THE WAY YOUR IMMUNE SYSTEM

355
00:12:35,920 --> 00:12:37,240
DOES THIS IS THAT IT HAS

356
00:12:37,240 --> 00:12:38,240
MULTIPLE DIFFERENT BRANCHES AND

357
00:12:38,240 --> 00:12:39,840
THEY DO SO IN DIFFERENT WAYS.

358
00:12:39,840 --> 00:12:41,080
AND I THINK MAYBE SOME OTHER

359
00:12:41,080 --> 00:12:43,440
SPEAKERS WILL TALK ABOUT THE

360
00:12:43,440 --> 00:12:45,720
DIVERSITY OF MEMORY B CELLS, I

361
00:12:45,720 --> 00:12:48,040
WILL COME BACK IN A BIT BUT ALSO

362
00:12:48,040 --> 00:12:49,880
T-CELLS FIGHT VARIANTS.

363
00:12:49,880 --> 00:12:53,280
SO IN WORK LED BY ALEX SETTI,

364
00:12:53,280 --> 00:12:55,680
FIRST QUESTION WAS REALLY HOW

365
00:12:55,680 --> 00:12:57,440
DIVERSE ARE T-CELL RESPONSES TO

366
00:12:57,440 --> 00:12:57,920
THIS VIRUS?

367
00:12:57,920 --> 00:13:00,560
BECAUSE IF YOU JUST HAVE ONE OR

368
00:13:00,560 --> 00:13:02,280
TWO PIECES OF THE VIRUS,

369
00:13:02,280 --> 00:13:04,200
EPITOPES OF THE VIRUS BEING

370
00:13:04,200 --> 00:13:06,120
RECOGNIZE, THEN THERE'S A

371
00:13:06,120 --> 00:13:07,040
CONCERN IF THE VIRUS RECOGNIZES

372
00:13:07,040 --> 00:13:10,480
ONE OF THOSE EPITOPES MAYBE 50%

373
00:13:10,480 --> 00:13:11,640
T-CELL RESPONSE AND YOU WOULD BE

374
00:13:11,640 --> 00:13:13,000
MANY BIG TROUBLE BUT INSTEAD

375
00:13:13,000 --> 00:13:16,440
WHAT THE SETTI LAB FOUND WAS

376
00:13:16,440 --> 00:13:18,360
THAT YOUR AVERAGE PERSON IS

377
00:13:18,360 --> 00:13:21,240
RECOGNIZING 30 TO 40 EPITOPES.

378
00:13:21,240 --> 00:13:23,320
SO IF THE VIRUS MYTASE A COUPLE

379
00:13:23,320 --> 00:13:25,200
OF THOSE EPITOPES IT IS NOT A

380
00:13:25,200 --> 00:13:27,360
BIG DEAL BECAUSE YOU HAVE MANY

381
00:13:27,360 --> 00:13:28,760
ESSENTIALLY LAYERS OR DIVERSITY

382
00:13:28,760 --> 00:13:31,080
OF T-CELL RESPONSES TO

383
00:13:31,080 --> 00:13:32,640
PROTECTION YOU IN THE CONTEXT

384
00:13:32,640 --> 00:13:33,760
THIS WAS INITIALLY IN THE

385
00:13:33,760 --> 00:13:35,600
CONTEXT OF INFECTION SO NOW WE

386
00:13:35,600 --> 00:13:36,640
HAVE GONE AND DONE THAT IN THE

387
00:13:36,640 --> 00:13:38,200
CONTEXT OF VACCINATION AND IN

388
00:13:38,200 --> 00:13:40,120
THE CONTEXT OF OMICRON.

389
00:13:40,120 --> 00:13:41,440
THE TWO SLIDES SUMMARY OF THAT

390
00:13:41,440 --> 00:13:43,120
WORK WHICH IS YOU CAN P LEARNED

391
00:13:43,120 --> 00:13:44,600
LAST WEEK IN CELL WAS THAT

392
00:13:44,600 --> 00:13:46,200
T-CELL RECOGNITION OF OMICRON

393
00:13:46,200 --> 00:13:48,280
WAS PREDICTED TO BE PRESERVED

394
00:13:48,280 --> 00:13:50,120
AND HERE ARE THE PREDICTIONS

395
00:13:50,120 --> 00:13:52,920
HERE, AND IT IS EVEN BETTER THAN

396
00:13:52,920 --> 00:13:54,320
THESE NUMBERS BECAUSE MOST OF

397
00:13:54,320 --> 00:13:55,880
THOSE ARE EVEN STILL PRESERVED

398
00:13:55,880 --> 00:13:57,440
WHICH I WON'T GO INTO BECAUSE OF

399
00:13:57,440 --> 00:13:59,040
TIME BUT IN THE ACTUAL DATA THE

400
00:13:59,040 --> 00:14:00,840
EXPERIMENTAL MEASUREMENTS IN

401
00:14:00,840 --> 00:14:02,240
VACCINATED PEOPLE, PEOPLE WHO

402
00:14:02,240 --> 00:14:04,280
RECEIVED EITHER THE PFIZER

403
00:14:04,280 --> 00:14:07,000
VACCINE OR THE MODERNA VACCINE,

404
00:14:07,000 --> 00:14:08,840
THEIR T-CELL RECOGNITION OF WIDE

405
00:14:08,840 --> 00:14:11,160
RANGE OF VARIANTS INCLUDING

406
00:14:11,160 --> 00:14:12,600
OMICRON HERE T THE END WAS

407
00:14:12,600 --> 00:14:13,960
ESSENTIALLY STABLE BOTH FOR THE

408
00:14:13,960 --> 00:14:17,120
CD4 T-CELLS AND THE CD8 T-CELLS

409
00:14:17,120 --> 00:14:18,200
LOOKING AT SPIKE.

410
00:14:18,200 --> 00:14:22,400
SO THAT'S POSITIVE NEWS IF

411
00:14:22,400 --> 00:14:23,160
T-CELL CON VARIATION OF

412
00:14:23,160 --> 00:14:24,280
RECOGNITION -- CONSERVATION OF

413
00:14:24,280 --> 00:14:26,320
RECOGNITION OF VARIANTS.

414
00:14:26,320 --> 00:14:28,240
ANTIBODIES HAD MORE TROUBLE AND

415
00:14:28,240 --> 00:14:30,920
I WILL COVER MEMORY B CELLS

416
00:14:30,920 --> 00:14:32,040
BRIEFLY.

417
00:14:32,040 --> 00:14:35,080
SO WHY ARE THERE CHALLENGES WITH

418
00:14:35,080 --> 00:14:35,480
PROTECTION?

419
00:14:35,480 --> 00:14:37,640
TO CONCEPTUALIZE THIS, THIS IS

420
00:14:37,640 --> 00:14:40,240
ONE WORKING MODEL OF THIS THAT

421
00:14:40,240 --> 00:14:42,200
TO PROTECT YOU AGAINST

422
00:14:42,200 --> 00:14:43,280
DETECTABLE INFECTION

423
00:14:43,280 --> 00:14:46,040
NEUTRALIZING ANTIBODIES ARE THE

424
00:14:46,040 --> 00:14:48,240
MAJOR FACT TORR THERE AND

425
00:14:48,240 --> 00:14:50,920
T-CELLS ARE MINOR FACTOR, TO

426
00:14:50,920 --> 00:14:52,680
PROTECT YOU AGAINST SERIOUS

427
00:14:52,680 --> 00:14:54,960
DISEASE NEUTRALIZING ANTIBODIES

428
00:14:54,960 --> 00:14:56,120
CONTRIBUTE BUT OTHER PARTS OF

429
00:14:56,120 --> 00:14:57,840
IMMUNE SYSTEM LIKELY CONTRIBUTE

430
00:14:57,840 --> 00:14:59,640
TO YOUR NEUTRALIZING ANTIBODY

431
00:14:59,640 --> 00:15:02,640
RECOGNITION OF OMICRON IS VERY

432
00:15:02,640 --> 00:15:04,440
POOR AFTER TWO VACCINATIONS.

433
00:15:04,440 --> 00:15:06,120
BUT THESE OTHER COMPONENTS OF

434
00:15:06,120 --> 00:15:10,040
IMMUNITY ARE QUITE CONSERVED.

435
00:15:10,040 --> 00:15:12,960
THIS REALLY IS PROBABLY TRUE FOR

436
00:15:12,960 --> 00:15:15,440
MANY ASPECTS OF IMMUNITY, THIS

437
00:15:15,440 --> 00:15:16,840
IS A LAYERED DEFENSE TYPE MODEL

438
00:15:16,840 --> 00:15:19,160
WHICH IS TRUE FOR MANY THINGS,

439
00:15:19,160 --> 00:15:21,480
NOT JUST IMMUNE THE I, SOMETIMES

440
00:15:21,480 --> 00:15:22,720
CALLED THE SWISS CHEESE MODEL,

441
00:15:22,720 --> 00:15:24,040
IF YOU HAVE MULTIPLE LAYERS THAT

442
00:15:24,040 --> 00:15:26,280
IMPROVE YOUR SUCCESS IN

443
00:15:26,280 --> 00:15:27,920
NEUTRALIZING ANTIBODIES ARE YOUR

444
00:15:27,920 --> 00:15:28,800
FIRST LAYER OF DEFENSE.

445
00:15:28,800 --> 00:15:30,600
IF THE VIRUS GETS THROUGH THAT

446
00:15:30,600 --> 00:15:32,080
FIRST LAYER OF DEFENSE IT IS NO

447
00:15:32,080 --> 00:15:33,240
SURPRISE HELPFUL TO HAVE

448
00:15:33,240 --> 00:15:36,640
MULTIPLE ADDITIONAL LAYERS OF

449
00:15:36,640 --> 00:15:38,040
DEFENSE AND WE IN MANY LABS HAVE

450
00:15:38,040 --> 00:15:39,760
BEEN TRYING TO UNDERSTAND THOSE

451
00:15:39,760 --> 00:15:40,960
DIFFERENT LAYERS.

452
00:15:40,960 --> 00:15:43,880
THIS IS CONSISTENT WITH THE

453
00:15:43,880 --> 00:15:44,600
EPIDEMIOLOGICAL DATA IN THE

454
00:15:44,600 --> 00:15:46,040
UNITED STATES, THIS IS ONE OF

455
00:15:46,040 --> 00:15:48,120
THE MOST PROMINENT OF THESE IN

456
00:15:48,120 --> 00:15:52,000
THE U.S., THAT OBSERVED PRIOR TO

457
00:15:52,000 --> 00:15:54,720
OMICRONNEN WANING OF PROTECTION

458
00:15:54,720 --> 00:15:55,440
AGAINST DETECTABLE INFECTION,

459
00:15:55,440 --> 00:15:57,240
POSITIVE CASES, BUT OVER THE

460
00:15:57,240 --> 00:15:59,400
COURSE OF SIX MONTHS BUT AFTER

461
00:15:59,400 --> 00:16:01,360
THE PFIZER VACCINE BUT NOT

462
00:16:01,360 --> 00:16:02,840
WANING OF PROTECTION AGAINST

463
00:16:02,840 --> 00:16:04,560
HOSPITALIZATIONS OR DEATH.

464
00:16:04,560 --> 00:16:06,720
WHICH WOULD BE CONSISTENT WITH

465
00:16:06,720 --> 00:16:08,240
ESSENTIALLY THIS MULTIPLE LAYERS

466
00:16:08,240 --> 00:16:10,560
OF DEFENSE, THE FIRST LAYER

467
00:16:10,560 --> 00:16:11,920
PARTIALLY FAILING BUT ADDITIONAL

468
00:16:11,920 --> 00:16:13,960
LAYERS HOLDING UP.

469
00:16:13,960 --> 00:16:16,320
AND THIS CAN BE SEEN IN DATA

470
00:16:16,320 --> 00:16:17,840
FROM THE NIH VACCINE RESEARCH

471
00:16:17,840 --> 00:16:20,560
CENTER IN EMORY, AFTER TWO DOSES

472
00:16:20,560 --> 00:16:22,320
VACCINE, THERE IS ACTUALLY A

473
00:16:22,320 --> 00:16:24,080
LACK OF DURABILITY, YOU HAVE TWO

474
00:16:24,080 --> 00:16:25,240
THINGS ONGOING.

475
00:16:25,240 --> 00:16:26,280
THERE IS HOW LONG DOES THE

476
00:16:26,280 --> 00:16:28,080
IMMUNE MEMORY LAST AND HOW WELL

477
00:16:28,080 --> 00:16:30,040
DOES THE IMMUNE MEMORY RECOGNIZE

478
00:16:30,040 --> 00:16:32,680
PARTICULAR VARIANT.

479
00:16:32,680 --> 00:16:34,440
SO DATA EVEN OUT TO EIGHT MONTHS

480
00:16:34,440 --> 00:16:36,520
OR LONGER HAVE BEEN SEEN IN THAT

481
00:16:36,520 --> 00:16:39,440
THE ANTIBODY TITER ESSENTIALLY

482
00:16:39,440 --> 00:16:41,160
CONTINUOUSLY DECLINE FOR AT

483
00:16:41,160 --> 00:16:42,800
LEAST EIGHT MONTHS AFTER TWO

484
00:16:42,800 --> 00:16:44,200
DOSES RNA VACCINE.

485
00:16:44,200 --> 00:16:46,880
SO THESE VACCINES ARE DOING A

486
00:16:46,880 --> 00:16:48,760
GOOD JOB GENERATING T-CELLS

487
00:16:48,760 --> 00:16:51,360
MEMORY AND B CELL MEMORY BUT NOT

488
00:16:51,360 --> 00:16:53,080
GREAT JOB AFTER TWO DOSES

489
00:16:53,080 --> 00:16:54,640
GENERATING DURABLE ANTIBODIES SO

490
00:16:54,640 --> 00:16:56,160
WHY IS THAT THE CASE?

491
00:16:56,160 --> 00:16:59,240
SO HERE IS A SIMPLE MODEL

492
00:16:59,240 --> 00:17:02,200
SHOWING THIS, ACTUALLY THIS IS A

493
00:17:02,200 --> 00:17:04,200
-- FROM 20 YEARS AGO, I DREW

494
00:17:04,200 --> 00:17:06,640
THIS WITH RAFI.

495
00:17:06,640 --> 00:17:07,880
AFTER VACCINATION YOU TRY TO

496
00:17:07,880 --> 00:17:10,440
GENERATE MEMORY B CELLS AND

497
00:17:10,440 --> 00:17:12,840
DURABLE ANTIBODY RESPONSE

498
00:17:12,840 --> 00:17:14,280
THROUGH PLASMA CELLS BUT OTHER

499
00:17:14,280 --> 00:17:15,840
TYPES OF ANTIBODY SECRETING

500
00:17:15,840 --> 00:17:18,040
CELLS NOT JUST LONG LASTING ONES

501
00:17:18,040 --> 00:17:19,720
AN AFTER TWO DOSE VACCINATION

502
00:17:19,720 --> 00:17:21,840
YOU GENERATE GREAT NEUTRALIZING

503
00:17:21,840 --> 00:17:23,640
ANTIBODIES BUT MOSTLY SHORT

504
00:17:23,640 --> 00:17:25,240
LIVED SO A BIG QUESTION ABOUT

505
00:17:25,240 --> 00:17:26,640
DURABILITY HAS BEEN IF YOU GO

506
00:17:26,640 --> 00:17:28,240
FROM THE TWO DOSE REGIMEN TO A

507
00:17:28,240 --> 00:17:30,840
THREE DOSE REGIMEN, DOES

508
00:17:30,840 --> 00:17:32,520
DURABILITY STAY THE SAME, STAY

509
00:17:32,520 --> 00:17:35,240
SHORT LASTING, AND OR DO YOU

510
00:17:35,240 --> 00:17:37,440
START GENERATING MORE LONG LIVED

511
00:17:37,440 --> 00:17:38,880
PLASMA CELLS, POSSIBLY FROM

512
00:17:38,880 --> 00:17:39,680
MEMORY B CELLS.

513
00:17:39,680 --> 00:17:41,800
SO THE FIRST DATA ON THIS WAS

514
00:17:41,800 --> 00:17:44,440
REALLY MADE PUBLIC LAST WEEK

515
00:17:44,440 --> 00:17:45,960
BOTH FOR PFIZER VACCINE AND

516
00:17:45,960 --> 00:17:47,840
MODERNA VACCINE SO TO BRIEFLY

517
00:17:47,840 --> 00:17:52,120
SUMMARIZE WHAT IS IMPORTANT DATA

518
00:17:52,120 --> 00:17:59,400
HERE, IS THAT NOT MUCH

519
00:17:59,400 --> 00:18:00,440
DURABILITY AFTER TWO DOSE

520
00:18:00,440 --> 00:18:02,040
VACCINE BUT AFTER THREE DOSES

521
00:18:02,040 --> 00:18:04,440
WHAT IS OBSERVED IS ADDED FOUR

522
00:18:04,440 --> 00:18:06,000
MONTHS LESS THAN TWOFOLD DECLINE

523
00:18:06,000 --> 00:18:07,720
MANY THE NEUTRALIZING ANTIBODY

524
00:18:07,720 --> 00:18:10,280
TITERS AGAINST THE ANCESTRAL

525
00:18:10,280 --> 00:18:12,000
STRAIN, BETTER DURABILITY THAN

526
00:18:12,000 --> 00:18:13,400
OBSERVED AFTER TWO DOSES AND

527
00:18:13,400 --> 00:18:15,800
ALSO AGAINST OMICRON A SIMILAR

528
00:18:15,800 --> 00:18:17,440
DECLINE OUT OF FOUR MONTHS.

529
00:18:17,440 --> 00:18:19,920
SO THESE DATA I THINK HAVE TO BE

530
00:18:19,920 --> 00:18:21,720
CONSIDERED VERY ENCOURAGING NEWS

531
00:18:21,720 --> 00:18:26,240
ABOUT DURABILITY BUT AT THE SAME

532
00:18:26,240 --> 00:18:29,440
TIME THE NIH GROUPS PUBLISHED

533
00:18:29,440 --> 00:18:31,160
DATA LAST WEEK SHOWING THAT OUT

534
00:18:31,160 --> 00:18:32,920
AT SIX MONTHS AFTER THIRD DOSE

535
00:18:32,920 --> 00:18:34,440
COMPARED TO ONE MONTH THERE IS

536
00:18:34,440 --> 00:18:37,520
ONLY A TWOFOLD DECLINE IN

537
00:18:37,520 --> 00:18:39,000
NEUTRALIZING ANTIBODIES AGAINST

538
00:18:39,000 --> 00:18:40,640
ANCESTRAL SO VERY GOOD SIGN

539
00:18:40,640 --> 00:18:42,120
ANTIBODY DURABILITY IS MUCH

540
00:18:42,120 --> 00:18:43,520
GREATER AFTER THREE DOSES THAN

541
00:18:43,520 --> 00:18:45,880
TWO, BUT FOR OMICRON IT WAS A

542
00:18:45,880 --> 00:18:47,280
LITTLE MORE PERPLEXING WHERE

543
00:18:47,280 --> 00:18:48,960
THERE WAS A BIGGER DROP AND

544
00:18:48,960 --> 00:18:50,440
MAYBE WE CAN DISCUSS THAT LATER

545
00:18:50,440 --> 00:18:52,440
SO SOME POSITIVE NEWS BUT NOT

546
00:18:52,440 --> 00:18:56,240
PERFECT SO IN SUMMARY, LAYER

547
00:18:56,240 --> 00:18:57,120
IMMUNOLOGICAL DEFENSES ARE

548
00:18:57,120 --> 00:18:58,560
VALUABLE AND THESE VACCINES ARE

549
00:18:58,560 --> 00:19:02,240
GENERATING MULTIPLE LAYERS OF

550
00:19:02,240 --> 00:19:02,840
IMMUNOLOGICAL DEFENSE.

551
00:19:02,840 --> 00:19:04,440
MANY OF THOSE LAYERS ARE GOOD

552
00:19:04,440 --> 00:19:06,520
AFTER TWO DOSES, BUT REALLY

553
00:19:06,520 --> 00:19:09,440
THESE RNA VACCINES LOOK LIKE

554
00:19:09,440 --> 00:19:11,640
THEIR THREE DOSE REGIMENS

555
00:19:11,640 --> 00:19:13,520
GENERATE DURABLE ANTIBODIES IN

556
00:19:13,520 --> 00:19:16,360
GENERAL AS WELL AS NEUTRALIZING

557
00:19:16,360 --> 00:19:17,640
ANTIBODIES THAT RECOGNIZE

558
00:19:17,640 --> 00:19:19,320
OMICRON AT ALL AND THAT'S COMING

559
00:19:19,320 --> 00:19:20,960
FROM MEMORY B CELLS THAT MATURE

560
00:19:20,960 --> 00:19:21,840
AND OTHER SPEAKERS CAN COMMENT

561
00:19:21,840 --> 00:19:23,840
ON THAT AS WELL AS NOW AFTER THE

562
00:19:23,840 --> 00:19:25,520
THIRD DOSE GENERATING MORE OF

563
00:19:25,520 --> 00:19:27,440
THESE DURABLE ANTIBODY RESPONSES

564
00:19:27,440 --> 00:19:29,120
BUT PERHAPS NOT PERFECTLY.

565
00:19:29,120 --> 00:19:30,680
IN THE INTEREST OF TIME, I'M

566
00:19:30,680 --> 00:19:32,200
GOING TO SHOW THIS

567
00:19:32,200 --> 00:19:34,040
ACKNOWLEDGMENT SLIDE, I WORK AT

568
00:19:34,040 --> 00:19:36,480
LJI, CERTAINLY PART OF HUGE TEAM

569
00:19:36,480 --> 00:19:39,680
EFFORT, AND I WANT TO CALL OUT

570
00:19:39,680 --> 00:19:43,080
(INDISCERNIBLE) WHO DID AMAZING

571
00:19:43,080 --> 00:19:44,680
JOB LEADING THE OMICRON STUDY

572
00:19:44,680 --> 00:19:45,840
WITH LOTS OF PEOPLE WORKING

573
00:19:45,840 --> 00:19:47,000
THROUGH THE HOLIDAYS TO GET THE

574
00:19:47,000 --> 00:19:47,800
DATA PUBLIC.

575
00:19:47,800 --> 00:19:50,880
I WILL STOP THERE.

576
00:19:50,880 --> 00:19:55,480
RAFI AND DONNA.

577
00:19:55,480 --> 00:19:57,120
>> THANK YOU VERY MUCH.

578
00:19:57,120 --> 00:19:58,640
REALLY INTERESTING DATA.

579
00:19:58,640 --> 00:20:06,760
I DON'T KNOW IF YOU CAN SEE.

580
00:20:06,760 --> 00:20:08,640
SO WE'LL TAKE A FEW QUESTIONS

581
00:20:08,640 --> 00:20:09,800
FOR EACH TALK THEN HAVE

582
00:20:09,800 --> 00:20:16,720
DISCUSSION AT THE END.

583
00:20:16,720 --> 00:20:20,000
YOU HAVE THE DIFFERENT RESPONSES

584
00:20:20,000 --> 00:20:22,320
AND DIFFERENT KINETICS TO

585
00:20:22,320 --> 00:20:26,000
OMICRON VERSUS THE OTHER

586
00:20:26,000 --> 00:20:26,640
VARIANTS?

587
00:20:26,640 --> 00:20:29,240
CAN YOU EXPLAIN WHY THAT MIGHT

588
00:20:29,240 --> 00:20:30,720
BE, LIKE DIFFERENT KINETICS FOR

589
00:20:30,720 --> 00:20:31,520
THAT?

590
00:20:31,520 --> 00:20:33,040
>> NO.

591
00:20:33,040 --> 00:20:34,600
I DIDN'T ANTICIPATE THAT, SO

592
00:20:34,600 --> 00:20:37,640
IT'S GOING TO BE IMPORTANT TO

593
00:20:37,640 --> 00:20:39,600
SEE DATA FROM MORE GROUPS REALLY

594
00:20:39,600 --> 00:20:41,800
I HAVE BEEN SAYING FOR QUITE A

595
00:20:41,800 --> 00:20:43,040
WHILE THAT THE FACT THAT AFTER

596
00:20:43,040 --> 00:20:44,840
TWO DOSES OF VACCINE THE

597
00:20:44,840 --> 00:20:46,240
ANTIBODY TITERS DROP PRETTY

598
00:20:46,240 --> 00:20:48,040
QUICKLY, THAT'S NOT TOO

599
00:20:48,040 --> 00:20:50,240
SURPRISING, LOTS OF VACCINES ARE

600
00:20:50,240 --> 00:20:51,360
THREE DOSE REGIMENS.

601
00:20:51,360 --> 00:20:53,840
AND TO GENERATE THOSE DURABLE

602
00:20:53,840 --> 00:20:55,000
ANTIBODY RESPONSES IT CAN JUST

603
00:20:55,000 --> 00:20:58,360
TAKE AN ADDITIONAL DOSE TO

604
00:20:58,360 --> 00:20:59,520
CONVINCE YOUR IMMUNE SYSTEM THAT

605
00:20:59,520 --> 00:21:00,760
IT IS WORTH THE RESOURCES TO GET

606
00:21:00,760 --> 00:21:02,720
THAT LONGEVITY.

607
00:21:02,720 --> 00:21:04,240
AND THAT DOES LOOK LIKE THAT'S

608
00:21:04,240 --> 00:21:09,760
TURNING OUT TO BE TRUE, AT LEAST

609
00:21:09,760 --> 00:21:12,080
FOR THE QUOTE UNQUOTE BASIC

610
00:21:12,080 --> 00:21:14,040
NEUTRALIZING ANTIBODY, PFIZER AN

611
00:21:14,040 --> 00:21:15,040
MODERNA REPORTS THAT.

612
00:21:15,040 --> 00:21:16,160
BUT WHY OMICRON WOULD BE

613
00:21:16,160 --> 00:21:19,360
DIFFERENT MANY THE MODERNA DATA

614
00:21:19,360 --> 00:21:24,360
IS ACTUALLY HARD FOR ME TO

615
00:21:24,360 --> 00:21:24,880
EXPLAIN.

616
00:21:24,880 --> 00:21:28,200
>> SHANE, HOW MUCH OF THAT

617
00:21:28,200 --> 00:21:30,040
(INAUDIBLE)

618
00:21:30,040 --> 00:21:31,760
>> CAN YOU GUYS HEAR ME?

619
00:21:31,760 --> 00:21:33,040
>> HOW MIGHT WHAT?

620
00:21:33,040 --> 00:21:34,840
>> SORRY.

621
00:21:34,840 --> 00:21:35,800
SHANE CAN YOU HEAR ME?

622
00:21:35,800 --> 00:21:36,920
>> I'M SORRY.

623
00:21:36,920 --> 00:21:37,880
>> GOOD.

624
00:21:37,880 --> 00:21:39,520
HOW MUCH OF THAT DIFFERENCE IN

625
00:21:39,520 --> 00:21:41,000
DURABILITY YOU THINK IS DISTANCE

626
00:21:41,000 --> 00:21:43,760
BETWEEN THE FIRST TWO SHOTS

627
00:21:43,760 --> 00:21:45,440
VERSUS TWO VERSUS THREE?

628
00:21:45,440 --> 00:21:48,000
I THINK THE VACCINE WORLD WE

629
00:21:48,000 --> 00:21:49,760
HAVE KNOWN FOR A WHILE THE

630
00:21:49,760 --> 00:21:50,800
CLOSER YOU U PUT THE PRIME OF

631
00:21:50,800 --> 00:21:53,040
THE BOOST THE MORE YOU SEEM TO

632
00:21:53,040 --> 00:21:54,800
AUGMENT SORT OF SHORT TERM

633
00:21:54,800 --> 00:21:57,080
EFFECTOR PLASMA BLAST KIND OF

634
00:21:57,080 --> 00:21:59,160
RESPONSES VERSUS LONG LIVED

635
00:21:59,160 --> 00:22:00,640
PLASMA CELL SO IS THERE ANY --

636
00:22:00,640 --> 00:22:04,200
NOT AWARE OF ANY DATA INTENTION

637
00:22:04,200 --> 00:22:05,360
AILINGLY SPREAD OUT THOSE FIRST

638
00:22:05,360 --> 00:22:07,040
TWO mRNA DOSES LONGER AND THEN

639
00:22:07,040 --> 00:22:08,880
ASK THE DURABILITY QUESTION.

640
00:22:08,880 --> 00:22:13,480
>> THOSE DATA ARE AVAILABLE TO

641
00:22:13,480 --> 00:22:15,680
AN EXTENT FROM THE UK AND CANADA

642
00:22:15,680 --> 00:22:18,000
THAT SPREAD OUT DOSES TO EITHER

643
00:22:18,000 --> 00:22:20,480
8, 12 OR 16 WEEKS.

644
00:22:20,480 --> 00:22:22,640
AND I HAVEN'T SEEN ANY PUBLISHED

645
00:22:22,640 --> 00:22:24,360
DATA THAT HAVE INDICATED THAT

646
00:22:24,360 --> 00:22:25,880
DURABILITY IS BETTER THERE.

647
00:22:25,880 --> 00:22:27,440
IT WOULD BE -- I HAVEN'T SEEN

648
00:22:27,440 --> 00:22:28,320
DATA PUBLISHED -- I DON'T

649
00:22:28,320 --> 00:22:29,960
REMEMBER IF I SAW DATA OUT TO

650
00:22:29,960 --> 00:22:32,000
SIX MONTHS BUT AT LEAST SHORTER

651
00:22:32,000 --> 00:22:35,960
THAN THAT DIDN'T SEE A BIG

652
00:22:35,960 --> 00:22:36,400
SHIFT.

653
00:22:36,400 --> 00:22:37,800
BUT IT IS A GOOD QUESTION.

654
00:22:37,800 --> 00:22:40,080
>> SO THE THIRD MAYBE MORE

655
00:22:40,080 --> 00:22:42,560
DETERMINANT THAN NECESSARILY THE

656
00:22:42,560 --> 00:22:43,760
DISTANCE BETWEEN SHOTS IN YOUR

657
00:22:43,760 --> 00:22:45,200
TAKE.

658
00:22:45,200 --> 00:22:46,200
>> YEAH.

659
00:22:46,200 --> 00:22:47,640
AND I THINK THAT'S BEEN THE

660
00:22:47,640 --> 00:22:50,640
HISTORY OF SOME OTHER VACCINES.

661
00:22:50,640 --> 00:22:54,480
IT'S AFTER TWO DOSES IT IS A --

662
00:22:54,480 --> 00:22:56,800
OF SAY HEPATITIS B, EVEN IF

663
00:22:56,800 --> 00:22:58,480
EIGHT WEEKS APART THERE'S NOT

664
00:22:58,480 --> 00:23:00,200
MUCH ANTIBODY MAINTENANCE UNTIL

665
00:23:00,200 --> 00:23:02,440
YOU GET THAT THIRD DOSE.

666
00:23:02,440 --> 00:23:04,040
BUT IT WOULD BE GREAT TO HAVE

667
00:23:04,040 --> 00:23:05,760
MORE DATA ON IT.

668
00:23:05,760 --> 00:23:08,840
>> THIS IS -- (OVERLAPPING

669
00:23:08,840 --> 00:23:09,080
SPEAKERS)

670
00:23:09,080 --> 00:23:10,640
>> ALISON YOU HAVE YOUR HAND UP.

671
00:23:10,640 --> 00:23:13,160
>> NO, SHE CAN GO.

672
00:23:13,160 --> 00:23:16,200
>> OKAY.

673
00:23:16,200 --> 00:23:17,720
>> I DON'T KNOW IF THIS WILL BE

674
00:23:17,720 --> 00:23:19,680
COVERED BUT THANK YOU FOR THE

675
00:23:19,680 --> 00:23:20,400
PRESENTATION, SHANE.

676
00:23:20,400 --> 00:23:23,280
MY QUESTION HAS TO DO WITH EXTRA

677
00:23:23,280 --> 00:23:25,680
FOLLICULAR ANTIBODY RESPONSES

678
00:23:25,680 --> 00:23:27,760
REPORTED FROM THE MA GROUP AND

679
00:23:27,760 --> 00:23:29,920
ELSEWHERE TOO, HOW DOES THAT

680
00:23:29,920 --> 00:23:31,440
FACTOR IN AND THEN HAVING

681
00:23:31,440 --> 00:23:32,880
CONCERNS ABOUT THAT BEING

682
00:23:32,880 --> 00:23:34,360
PROTECTIVE VERSUS NOT, WOULD YOU

683
00:23:34,360 --> 00:23:35,440
COMMENT ON THAT?

684
00:23:35,440 --> 00:23:36,000
>> SURE.

685
00:23:36,000 --> 00:23:38,040
JUST BRIEFLY BECAUSE I MEAN

686
00:23:38,040 --> 00:23:39,120
THESE ARE GREAT QUESTIONS, IT

687
00:23:39,120 --> 00:23:40,640
WOULD BE GOOD TO KEEP ALL THEM

688
00:23:40,640 --> 00:23:42,840
IN MIND AS WE GO THROUGH THAT.

689
00:23:42,840 --> 00:23:45,720
SO HERE I SPECIFICALLY FOCUS ON

690
00:23:45,720 --> 00:23:47,680
VACCINE RESPONSES.

691
00:23:47,680 --> 00:23:49,920
AND SO ACTUALLY YOU CAN SEE MANY

692
00:23:49,920 --> 00:23:53,640
THIS MODEL HERE YOU GET EXTRA

693
00:23:53,640 --> 00:23:54,640
FOLLICULAR RESPONSES TO AT LEAST

694
00:23:54,640 --> 00:23:56,840
SOME VACCINES AS WELL AS

695
00:23:56,840 --> 00:23:58,400
INFECTIONS AND THESE SHORT LIVED

696
00:23:58,400 --> 00:24:02,600
RESPONSES CAN BE EITHER PRIOR TO

697
00:24:02,600 --> 00:24:04,760
OR AFTER AND YOU DEFINITELY ARE

698
00:24:04,760 --> 00:24:09,200
GETTING THESE TWO THE RNA

699
00:24:09,200 --> 00:24:11,560
VACCINES.  THIS IS ACTUALLY A

700
00:24:11,560 --> 00:24:14,440
VIRUS THAT AT LEAST ANCESTRAL

701
00:24:14,440 --> 00:24:15,440
STRAIN IS STRAIGHT FORWARD TO

702
00:24:15,440 --> 00:24:16,840
MAKE SOME NEUTRALIZING

703
00:24:16,840 --> 00:24:17,160
ANTIBODIES.

704
00:24:17,160 --> 00:24:20,400
YOU CAN HAVE A FEW UNMUTATED B

705
00:24:20,400 --> 00:24:22,040
CELLS THAT MAKE NEUTRALIZING

706
00:24:22,040 --> 00:24:25,040
ANTIBODIES SO EXTRA FOLLICULAR

707
00:24:25,040 --> 00:24:25,800
RESPONSE CAN BEOR CAN BE

708
00:24:25,800 --> 00:24:28,120
POSITIVE FOR GENERATING RAPID

709
00:24:28,120 --> 00:24:29,840
ANTIBODY RESPONSES BUT DO

710
00:24:29,840 --> 00:24:30,840
RECOGNIZE AND GERMINAL CENTER

711
00:24:30,840 --> 00:24:32,120
RESPONSE THE FURTHER MUTATE

712
00:24:32,120 --> 00:24:34,640
THOSE FOR HIGHER AFFINITY CELLS

713
00:24:34,640 --> 00:24:37,280
AND FOR THIS ANTIGEN HAVING BOTH

714
00:24:37,280 --> 00:24:39,200
PATHWAYS IS QUITE PRODUCTIVE AND

715
00:24:39,200 --> 00:24:41,280
IN THE CASE OF VACCINES IT IS

716
00:24:41,280 --> 00:24:42,320
REALLY NOT THOUGHT THAT THE

717
00:24:42,320 --> 00:24:45,960
EXTRA FOLLICULAR PATHWAY

718
00:24:45,960 --> 00:24:47,680
DETRACTS AT ALL FROM THE

719
00:24:47,680 --> 00:24:51,480
GERMINAL CENTER IN LONG LIVED,

720
00:24:51,480 --> 00:24:55,000
THE BEST DATA FROM ROB BRINK AND

721
00:24:55,000 --> 00:24:56,640
COLLEAGUES IS THAT BOTH PATHWAYS

722
00:24:56,640 --> 00:25:00,240
OCCUR IN PARALLEL AND DON'T

723
00:25:00,240 --> 00:25:03,280
DETRACT FROM THERE.

724
00:25:03,280 --> 00:25:04,800
>> WE SHOULD MOVE ON.

725
00:25:04,800 --> 00:25:07,160
>> YES.

726
00:25:07,160 --> 00:25:07,400
>> OKAY.

727
00:25:07,400 --> 00:25:10,040
ALL RIGHT.

728
00:25:10,040 --> 00:25:10,680
SO THANK YOU VERY MUCH, SHANE.

729
00:25:10,680 --> 00:25:13,680
SO THE NEXT SPEAKER WILL BE

730
00:25:13,680 --> 00:25:15,240
MARION PEPPER FROM UNIVERSITY OF

731
00:25:15,240 --> 00:25:17,040
WASHINGTON AND SHE WILL BE

732
00:25:17,040 --> 00:25:18,400
PRESENTING DIFFERENCES IN IMMUNE

733
00:25:18,400 --> 00:25:21,640
MEMORY RESPONSES IN VACCINATED

734
00:25:21,640 --> 00:25:24,000
PREVIOUSLY AFFECTED OR NAIVE

735
00:25:24,000 --> 00:25:24,440
INDIVIDUALS.

736
00:25:24,440 --> 00:25:40,960
SHARE YOUR SCREEN MARION.

737
00:25:40,960 --> 00:25:42,600
>> THANKS FOR HAVING ME, THIS IS

738
00:25:42,600 --> 00:25:44,640
REALLY EXCITING TO BE ABLE TALK

739
00:25:44,640 --> 00:25:46,920
ABOUT ALL THESE CONCEPTS WITH

740
00:25:46,920 --> 00:25:47,200
EVERYONE.

741
00:25:47,200 --> 00:25:50,080
SO I'M GOING TO BE TALKING ABOUT

742
00:25:50,080 --> 00:25:52,320
HOW WE HAVE LOOKED AT THE IMMUNE

743
00:25:52,320 --> 00:25:53,040
RESPONSE THAT HAS FORMED IN

744
00:25:53,040 --> 00:25:55,120
PEOPLE WHO ARE EITHER INFECTED

745
00:25:55,120 --> 00:25:56,720
AND THEN VACCINATED OR JUST

746
00:25:56,720 --> 00:25:58,560
VACCINATED ALONE.

747
00:25:58,560 --> 00:26:01,440
AND HOPEFULLY THIS CAN ACTUALLY

748
00:26:01,440 --> 00:26:02,840
GET TO ANSWER SOME OF ROSS'S

749
00:26:02,840 --> 00:26:03,720
QUESTIONS THAT WE CAN TALK ABOUT

750
00:26:03,720 --> 00:26:06,920
IN A LITTLE BIT.

751
00:26:06,920 --> 00:26:08,600
SO WHAT I'M GOING TO BE TALKING

752
00:26:08,600 --> 00:26:11,960
ABOUT HERE IS BASICALLY ARE

753
00:26:11,960 --> 00:26:13,120
THERE CHARACTERISTICS FROM A

754
00:26:13,120 --> 00:26:15,640
PRIMARY IMMUNE RESPONSE IN WHICH

755
00:26:15,640 --> 00:26:18,400
IMMUNE NAIVE INDIVIDUALS RETAIN

756
00:26:18,400 --> 00:26:20,480
THESE ATTRIBUTES IN THEIR MEMORY

757
00:26:20,480 --> 00:26:22,960
CELL POPULATIONS THAT THEN

758
00:26:22,960 --> 00:26:26,080
IMPACT THE REST OF THEIR IMMUNE

759
00:26:26,080 --> 00:26:30,960
RESPONSE TO VACCINATION.

760
00:26:30,960 --> 00:26:32,360
SOLD WE KNOW A LOT ABOUT IMMUNE

761
00:26:32,360 --> 00:26:35,480
MEMORY AND WHY IT PREVENTS

762
00:26:35,480 --> 00:26:37,960
DISEASE, YOU HAVE LONG LIVED

763
00:26:37,960 --> 00:26:41,320
QUIESCENT ENHANCED THAT CHANGES

764
00:26:41,320 --> 00:26:43,560
INCLUDING MEMORY B CELLS AN CD4,

765
00:26:43,560 --> 00:26:45,440
CD8 B CELLS AN LONG LIVED PLASMA

766
00:26:45,440 --> 00:26:46,640
CELLS RETAINED IN BONE MARROW

767
00:26:46,640 --> 00:26:54,680
THAT PRODUCE ANTIBODIES THEY

768
00:26:54,680 --> 00:26:56,480
INHERIT CHARACTERISTICS DURING

769
00:26:56,480 --> 00:26:57,440
THE DIFFERENTIATION PROCESS MANY

770
00:26:57,440 --> 00:27:01,520
THE PRIMARY IMMUNE RESPONSE THAT

771
00:27:01,520 --> 00:27:03,040
BULLIES THEM TO BE ABLE TO

772
00:27:03,040 --> 00:27:04,680
RESPOND FUNCTIONALLY IN

773
00:27:04,680 --> 00:27:06,400
DIFFERENT WAYS THAN IN THIS

774
00:27:06,400 --> 00:27:07,360
NAIVE STATE.

775
00:27:07,360 --> 00:27:09,080
THAT HAS THE ABILITY TO CONTROL

776
00:27:09,080 --> 00:27:13,040
INFECTION FASTER THAN NAIVE

777
00:27:13,040 --> 00:27:13,720
RESPONSE.

778
00:27:13,720 --> 00:27:15,080
WE ALSO KNOW THESE CELLS ARE

779
00:27:15,080 --> 00:27:16,200
LOCALIZED TO DIFFERENT REGIONS

780
00:27:16,200 --> 00:27:21,040
OF THE BODY BUT LARGELY FOR

781
00:27:21,040 --> 00:27:23,200
HUMAN STUDIES EXCEPT DONNA'S

782
00:27:23,200 --> 00:27:24,480
LOVELY IS THE DIS WE HAVE BEEN

783
00:27:24,480 --> 00:27:25,840
LIMITED TO LOOKING AT BLOOD SO

784
00:27:25,840 --> 00:27:27,080
MOST OF WHAT I WILL TALK ABOUT

785
00:27:27,080 --> 00:27:29,240
TODAY IS PERIPHERAL BLOOD

786
00:27:29,240 --> 00:27:29,640
RESPONSES.

787
00:27:29,640 --> 00:27:31,840
SO WHEN THE PANDEMIC EMERGED WE

788
00:27:31,840 --> 00:27:33,640
INITIATED STUDIES LOOKING IN

789
00:27:33,640 --> 00:27:35,800
INDIVIDUALS WHO HAD MILD

790
00:27:35,800 --> 00:27:37,640
INFECTION TO SEE WHAT TYPES OF

791
00:27:37,640 --> 00:27:40,000
IMMUNE RESPONSES THEY HAD AND

792
00:27:40,000 --> 00:27:40,440
LOUNGE THEY LASTED.

793
00:27:40,440 --> 00:27:42,200
WHAT WE WERE REALLY INTERESTED

794
00:27:42,200 --> 00:27:44,640
IN IS AT THREE MONTHS AFTER MILD

795
00:27:44,640 --> 00:27:48,080
INFECTION, DID INDIVIDUALS WHO

796
00:27:48,080 --> 00:27:49,560
HAD NO HOSPITALIZATION, MILD

797
00:27:49,560 --> 00:27:51,640
SYMPTOMS ACTUALLY DISPLAY

798
00:27:51,640 --> 00:27:53,440
CHARACTERISTICS OF IMMUNE MEMORY

799
00:27:53,440 --> 00:27:59,320
THAT WE WOULD THINK WOULD BE

800
00:27:59,320 --> 00:28:01,280
PROTECTIVE AND ASSOCIATED WITH

801
00:28:01,280 --> 00:28:01,920
IMMUNE VIRAL RESPONSE.

802
00:28:01,920 --> 00:28:04,120
WE WERE HAPPY TO SEE THIS,

803
00:28:04,120 --> 00:28:04,920
PUBLISHED LAST JANUARY.

804
00:28:04,920 --> 00:28:06,760
SO NOW WHAT WE HAVE DONE IS WE

805
00:28:06,760 --> 00:28:10,880
HAVE GONE ON TO KEEP TRACKING

806
00:28:10,880 --> 00:28:11,440
THIS RESPONSE.

807
00:28:11,440 --> 00:28:14,480
WHEN THERE IS A PANDEMIC

808
00:28:14,480 --> 00:28:15,120
UNFOLDING AROUND YOU, THERE ARE

809
00:28:15,120 --> 00:28:17,080
ALL SORTS OF INTERESTING IMMUNE

810
00:28:17,080 --> 00:28:17,960
CONDITIONS TO FOLLOW.

811
00:28:17,960 --> 00:28:20,720
AND TO STUDY.

812
00:28:20,720 --> 00:28:23,560
ONE OF THE THINGS THAT HAS

813
00:28:23,560 --> 00:28:24,960
EMERGED THROUGH THIS PANDEMIC IS

814
00:28:24,960 --> 00:28:28,800
THAT THERE ARE DIFFERENCES IN

815
00:28:28,800 --> 00:28:30,800
HOW INDIVIDUALS PREVIOUSLY

816
00:28:30,800 --> 00:28:32,440
INFECTS AND VACCINATED VERSUS

817
00:28:32,440 --> 00:28:35,600
VACCINATED ALONE HOW THEY

818
00:28:35,600 --> 00:28:37,360
RESPOND TO INFECTION.

819
00:28:37,360 --> 00:28:39,040
THAT HAS BEEN BOTH OF THE

820
00:28:39,040 --> 00:28:39,960
IMMUNOLOGICAL LEVEL, THIS IS

821
00:28:39,960 --> 00:28:43,160
WORK FROM CATHY PATE SHOWING

822
00:28:43,160 --> 00:28:44,920
DIFFERENCES IN THE POOLS OF

823
00:28:44,920 --> 00:28:48,160
MEMORY CELLS THAT CAN EMERGE

824
00:28:48,160 --> 00:28:49,840
BOTH HERE MEMORY CELLS AND THE

825
00:28:49,840 --> 00:28:51,600
SHORT LIVED PLASMA BLASTS THAT

826
00:28:51,600 --> 00:28:53,760
EMERGE FROM THOSE MEMORY CELLS.

827
00:28:53,760 --> 00:28:55,760
AFTER ONE DOSE OF mRNA VACCINE

828
00:28:55,760 --> 00:28:59,920
OR TWO DOSES OF mRNA VACCINE

829
00:28:59,920 --> 00:29:01,280
AND HOW THOSE CELLS PERSIST OVER

830
00:29:01,280 --> 00:29:02,440
TIME, YOU CAN SEE MORE MEMORY

831
00:29:02,440 --> 00:29:04,840
CELLS ARE RETAINED.

832
00:29:04,840 --> 00:29:07,480
AS WELL AS EPIDEMIOLOGICAL DATA

833
00:29:07,480 --> 00:29:09,840
WHICH HAVE SHOWN DIFFERENCES IN

834
00:29:09,840 --> 00:29:11,560
PROTECTION THOUGH THE VACCINES

835
00:29:11,560 --> 00:29:13,120
HAVE DONE AN AMAZING JOB

836
00:29:13,120 --> 00:29:16,760
PROTECTING PEOPLE FROM SERIOUS

837
00:29:16,760 --> 00:29:17,880
DISEASE, THE INDIVIDUALS WHO

838
00:29:17,880 --> 00:29:19,760
HAVE BEEN PREVIOUSLY INFECTED

839
00:29:19,760 --> 00:29:22,080
WERE ABLE TO HAVE LIGHTLY BETTER

840
00:29:22,080 --> 00:29:24,040
IMMUNE PROTECTION AGAINST

841
00:29:24,040 --> 00:29:25,920
INFECTION AS WELL.

842
00:29:25,920 --> 00:29:27,680
SO WE WERE REALLY INTERESTED IN

843
00:29:27,680 --> 00:29:29,680
TRACKING THIS IN THE SAME COHORT

844
00:29:29,680 --> 00:29:33,160
THAT WE INITIALLY STARTED

845
00:29:33,160 --> 00:29:34,400
TRACKING IN MARCH 2020.

846
00:29:34,400 --> 00:29:37,600
AND TRYING TO UNDERSTAND WHAT

847
00:29:37,600 --> 00:29:38,600
HYBRID IMMUNITY MIGHT MEAN AND

848
00:29:38,600 --> 00:29:40,040
WHAT ARE THE DIFFERENCES AND

849
00:29:40,040 --> 00:29:41,720
GETTING AT THAT QUESTION THAT

850
00:29:41,720 --> 00:29:44,000
ROSS ASKED AS TO WHETHER THIS IS

851
00:29:44,000 --> 00:29:45,200
JUST A DIFFERENCE IN THE NUMBER

852
00:29:45,200 --> 00:29:48,240
OF ANTIGEN DOSES WHICH OBVIOUSLY

853
00:29:48,240 --> 00:29:50,000
NAIVE INDIVIDUALS HAVE TWO DOSES

854
00:29:50,000 --> 00:29:52,240
OF VACCINE AND THEN PEOPLE ARE

855
00:29:52,240 --> 00:29:54,240
LOOKING AT THE EMERGING IMMUNE

856
00:29:54,240 --> 00:29:55,480
RESPONSE AT THAT POINT, WHILE

857
00:29:55,480 --> 00:29:57,120
PEOPLE WHO ARE PREVIOUSLY

858
00:29:57,120 --> 00:29:58,800
INFECTED HAVE THIS ADDITIONAL

859
00:29:58,800 --> 00:30:00,440
DOSE OF ANTIGEN FOLLOWED BY THE

860
00:30:00,440 --> 00:30:02,200
TWO VACCINES.

861
00:30:02,200 --> 00:30:04,240
WHAT MADE THIS A REALLY EVEN

862
00:30:04,240 --> 00:30:05,600
MORE INTERESTING STUDY WAS

863
00:30:05,600 --> 00:30:07,440
DURING THE TIME PERIODS WE WERE

864
00:30:07,440 --> 00:30:10,080
STUDYING THESE IMMUNE RESPONSES,

865
00:30:10,080 --> 00:30:12,200
NOT ONLY DID THE VACCINES EMERGE

866
00:30:12,200 --> 00:30:15,400
BUT ALSO THE ABILITY TO GET

867
00:30:15,400 --> 00:30:18,360
BOOSTED ALSO BECAME PART OF THE

868
00:30:18,360 --> 00:30:20,440
NORMAL REGIMEN FOR MOST PEOPLE

869
00:30:20,440 --> 00:30:22,360
ESPECIALLY PEOPLE OVER 65 BUT

870
00:30:22,360 --> 00:30:23,040
MOST PEOPLE.

871
00:30:23,040 --> 00:30:25,240
SO WE CAN ACTUALLY START TO

872
00:30:25,240 --> 00:30:27,840
TRACK HOW DID THESE IMMUNE

873
00:30:27,840 --> 00:30:29,760
RESPONSES COMPARE THIS THESE

874
00:30:29,760 --> 00:30:31,680
SARS COV-2 NAIVE INDIVIDUAL

875
00:30:31,680 --> 00:30:34,360
WHOSE ARE NEVER INFECTED BUT

876
00:30:34,360 --> 00:30:36,240
VACCINATED ONE, TWO, THREE TIMES

877
00:30:36,240 --> 00:30:37,680
VERSUS PREVIOUSLY INFECTED

878
00:30:37,680 --> 00:30:37,920
PEOPLE.

879
00:30:37,920 --> 00:30:40,640
WE CAN COMPARE THEIR SECOND DOSE

880
00:30:40,640 --> 00:30:42,640
WHICH WAS EQUIVALENT TO A THIRD

881
00:30:42,640 --> 00:30:45,320
DOSE IN THE SARS COV-2 NAIVE

882
00:30:45,320 --> 00:30:46,720
INDIVIDUALS TO GET AT WHETHER

883
00:30:46,720 --> 00:30:50,440
THIS WAS JUST AN ANTIGEN DOSE

884
00:30:50,440 --> 00:30:52,640
EXPERIENCE TYPE OF RESPONSE OR

885
00:30:52,640 --> 00:30:54,040
WHETHER THERE WAS SOMETHING

886
00:30:54,040 --> 00:30:55,840
INHERENTLY DIFFERENT ABOUT

887
00:30:55,840 --> 00:30:58,160
INFECTION THAT IMPRINTED

888
00:30:58,160 --> 00:30:59,960
CHARACTERISTICS OF THIS IMMUNE

889
00:30:59,960 --> 00:31:00,840
RESPONSE.

890
00:31:00,840 --> 00:31:03,400
SO MUCH LIKE MANY OTHERS WE LOOK

891
00:31:03,400 --> 00:31:05,480
AT THE THREE BASIC TENANTS OF

892
00:31:05,480 --> 00:31:06,080
IMMUNE MEMORY.

893
00:31:06,080 --> 00:31:08,880
WE LOOKED AT LONG LIVED PLASMA

894
00:31:08,880 --> 00:31:10,520
CELLS AND ANTIBODIES THAT WERE

895
00:31:10,520 --> 00:31:12,640
BEING SECRETED BY THOSE CELLS,

896
00:31:12,640 --> 00:31:14,240
AS WELL AS ANTIBODIES THAT WERE

897
00:31:14,240 --> 00:31:16,280
EMERGING FROM SHORT LIVED PLASMA

898
00:31:16,280 --> 00:31:17,800
BLASTS FROM MEMORY B CELLS.

899
00:31:17,800 --> 00:31:21,040
HERE WE ARE LOOKING AT BLUE IS

900
00:31:21,040 --> 00:31:22,920
THE INDIVIDUALS WHO HAD NEVER

901
00:31:22,920 --> 00:31:25,640
BEEN INFECT WITH SARS COV-2, WE

902
00:31:25,640 --> 00:31:28,840
DOUBLE CHECKED THIS BY ELISA,

903
00:31:28,840 --> 00:31:29,560
YOU CAN FOLLOW ANTIBODY

904
00:31:29,560 --> 00:31:31,320
RESPONSES TO THE RBD PORTION OF

905
00:31:31,320 --> 00:31:32,880
THE SPIKE PROTEIN AND WHAT YOU

906
00:31:32,880 --> 00:31:37,480
SEE IS THIS NICE BOOST, THAT

907
00:31:37,480 --> 00:31:41,080
DOES WEIGH IN AS DESCRIBED THIS

908
00:31:41,080 --> 00:31:43,080
IS SIX MONTHS POST VACCINE TWO

909
00:31:43,080 --> 00:31:45,400
BUT THIS IS A NICE BOOST AGAIN

910
00:31:45,400 --> 00:31:46,160
AFTER THIRD DOSE VACCINE.

911
00:31:46,160 --> 00:31:48,240
AND IF WE COMPARE THIS TO PEOPLE

912
00:31:48,240 --> 00:31:49,760
WHO WERE PREVIOUSLY INFECTED

913
00:31:49,760 --> 00:31:53,400
THEY TOO HAD A WANING IMMUNE

914
00:31:53,400 --> 00:31:54,240
RESPONSE.

915
00:31:54,240 --> 00:31:55,880
THIS TIME THIS PRE-VACCINE TIME

916
00:31:55,880 --> 00:31:58,760
POINT IS ABOUT A YEAR AFTER

917
00:31:58,760 --> 00:32:00,640
THEIR FIRST VACCINE BUT THAT

918
00:32:00,640 --> 00:32:02,640
ALSO IS BOOSTED TO HIGH LEVELS

919
00:32:02,640 --> 00:32:04,600
IN THESE INDIVIDUALS.

920
00:32:04,600 --> 00:32:06,360
WHEN YOU COMPARE THESE HEAD TO

921
00:32:06,360 --> 00:32:08,520
HEAD WHAT YOU CAN SEE IS THE

922
00:32:08,520 --> 00:32:10,160
VACCINES DO AN EXCELLENT JOB OF

923
00:32:10,160 --> 00:32:11,720
BOOSTING -- GETTING THE ANTIBODY

924
00:32:11,720 --> 00:32:13,840
RESPONSES UP TO ABOUT THE SAME

925
00:32:13,840 --> 00:32:15,960
LEVELS OF INDIVIDUALS WHO HAD

926
00:32:15,960 --> 00:32:17,440
HAD PREVIOUS INFECTION WHICH YOU

927
00:32:17,440 --> 00:32:18,640
CAN SEE HERE.

928
00:32:18,640 --> 00:32:20,640
BUT WHAT WAS INTERESTING TO US

929
00:32:20,640 --> 00:32:25,440
IS THAT THESE VACCINE INDUCED

930
00:32:25,440 --> 00:32:26,280
RESPONSES ONLY WANED MORE

931
00:32:26,280 --> 00:32:29,040
QUICKLY THAN INDIVIDUALS WHO HAD

932
00:32:29,040 --> 00:32:32,880
BEEN PREVIOUSLY INFECTED.

933
00:32:32,880 --> 00:32:34,640
THE BOOST HOWEVER SOMEWHAT

934
00:32:34,640 --> 00:32:35,840
AMELIORATED THIS TO THE POINT

935
00:32:35,840 --> 00:32:37,760
THIS DIFFERENCE IS NOT

936
00:32:37,760 --> 00:32:38,120
SIGNIFICANT.

937
00:32:38,120 --> 00:32:39,920
THIS IS DUE TO COMBINATION OF

938
00:32:39,920 --> 00:32:41,440
FACTORS, FIRST THERE IS NOT MUCH

939
00:32:41,440 --> 00:32:43,160
BOOST BETWEEN THE SECOND VACCINE

940
00:32:43,160 --> 00:32:46,040
SIX MONTHS TIME POINT AND THE

941
00:32:46,040 --> 00:32:47,440
THIRD BOOST IN INDIVIDUALS WHO

942
00:32:47,440 --> 00:32:48,840
HAVE BEEN PREVIOUSLY INFECTED

943
00:32:48,840 --> 00:32:51,680
WHILE THERE IS ONE FOR THOSE WHO

944
00:32:51,680 --> 00:32:55,800
WERE NAIVE AND THEIR IMMUNITY

945
00:32:55,800 --> 00:32:57,240
WANED HUMAN MORE IMMUNITY WANED

946
00:32:57,240 --> 00:32:59,000
SIGNIFICANTLY.

947
00:32:59,000 --> 00:33:02,000
WE CAN ALSO JUST CONCLUDE HERE,

948
00:33:02,000 --> 00:33:03,760
VACCINATION VIROD TO GET OPTIMAL

949
00:33:03,760 --> 00:33:05,840
ANTIBODY LEVELS FOR PREVIOUSLY

950
00:33:05,840 --> 00:33:06,840
INFECTED INDIVIDUALS SO IT

951
00:33:06,840 --> 00:33:08,640
REALLY HELPS FOR PREVIOUSLY

952
00:33:08,640 --> 00:33:11,120
INFECTED INDIVIDUALS TO GET

953
00:33:11,120 --> 00:33:13,280
VACCINATED BUT THEIR TITERS ARE

954
00:33:13,280 --> 00:33:15,080
BETTER MAINTAINED THAN IN NAIVE

955
00:33:15,080 --> 00:33:16,520
INDIVIDUALS AND THAT BOOST WAS

956
00:33:16,520 --> 00:33:18,200
NECESSARY TO GET OPTIMAL

957
00:33:18,200 --> 00:33:19,640
ANTIBODY LEVELS IN NAIVE

958
00:33:19,640 --> 00:33:20,560
INDIVIDUALS SUCH A THAT THEY

959
00:33:20,560 --> 00:33:22,440
WERE EQUIVALENTS TO THOSE WHO

960
00:33:22,440 --> 00:33:25,400
HAD BEEN PREVIOUSLY INFECTED.

961
00:33:25,400 --> 00:33:27,000
WE ALSO CHOSE TO LOOK AT MEMORY

962
00:33:27,000 --> 00:33:33,480
B CELLS TO SEE IF WE COULD FIND

963
00:33:33,480 --> 00:33:36,520
MEMORY B CELLS OF THE SPIKE

964
00:33:36,520 --> 00:33:37,680
PROTEIN AND TRACK HOW THEY

965
00:33:37,680 --> 00:33:38,840
CHANGE IN QUANTITY AND QUALITY

966
00:33:38,840 --> 00:33:39,280
OVER TIME.

967
00:33:39,280 --> 00:33:40,840
THIS IS SHOWING HOW WE LOOK AT

968
00:33:40,840 --> 00:33:42,640
THESE CELLS, WE CAN LOOK AT THE

969
00:33:42,640 --> 00:33:45,680
CELLS OF INTEREST VERSUS DECOY

970
00:33:45,680 --> 00:33:46,920
REAGENT THAT WAS DEVELOPED IN

971
00:33:46,920 --> 00:33:49,040
MARK JENKINS LAB AND IF WE LOOK

972
00:33:49,040 --> 00:33:51,640
AT THE NUMERICAL REPRESENTATION

973
00:33:51,640 --> 00:33:53,920
OF THESE ANTIGEN SPECIFIC B

974
00:33:53,920 --> 00:33:55,760
CELLS OVER TIME WE CAN ALSO SEE

975
00:33:55,760 --> 00:33:59,160
SIMILAR TRENDS TO WHAT WE SAW

976
00:33:59,160 --> 00:34:01,040
BEFORE WHEREAS THOSE INDIVIDUALS

977
00:34:01,040 --> 00:34:02,680
PREVIOUSLY INFECTED HAVE HIGHER

978
00:34:02,680 --> 00:34:04,200
NUMBERS OF MEMORY B CELLS THAT

979
00:34:04,200 --> 00:34:07,760
RESPOND TO RBD, THAT WAS BOOSTED

980
00:34:07,760 --> 00:34:13,480
BY THE VACCINE AGAIN STAYED

981
00:34:13,480 --> 00:34:15,240
HIGHER NUMBER, MAINTAINED BETTER

982
00:34:15,240 --> 00:34:16,840
MORE DURABLE RESPONSE THAN THOSE

983
00:34:16,840 --> 00:34:19,480
INDIVIDUALS VACCINATED ALONE BUT

984
00:34:19,480 --> 00:34:20,240
THE THIRD BOOR FOR THE

985
00:34:20,240 --> 00:34:23,240
INDIVIDUAL WHOSE HAD NOT BEEN

986
00:34:23,240 --> 00:34:24,640
PREVIOUSLY VACCINATED RAISED

987
00:34:24,640 --> 00:34:25,680
THEIR NUMBERS SO IT WAS NOT

988
00:34:25,680 --> 00:34:29,520
SIGNIFICANT HERE.

989
00:34:29,520 --> 00:34:32,960
WE FURTHER LOOK AT PHENOTYPE OF

990
00:34:32,960 --> 00:34:34,160
MEMORY CELLS, WHAT DID THEY LOOK

991
00:34:34,160 --> 00:34:35,520
LIKE AND QUALITIES DID THEY

992
00:34:35,520 --> 00:34:36,200
HAVE.

993
00:34:36,200 --> 00:34:39,240
WE HAD QUALITIES THAT WERE

994
00:34:39,240 --> 00:34:42,040
ASSOCIATED WITH INFECTION

995
00:34:42,040 --> 00:34:43,760
SPECIFICALLY CLASS SWITCHED,

996
00:34:43,760 --> 00:34:46,560
CLASSICAL MEMORY B CELLS WHICH

997
00:34:46,560 --> 00:34:49,240
RAPIDLY FORM ANTIBODY SECRETING

998
00:34:49,240 --> 00:34:50,480
PLASMA BLAST, THESE WERE HIGHER

999
00:34:50,480 --> 00:34:54,880
LEVELS BEFORE VACCINATION AND

1000
00:34:54,880 --> 00:34:57,120
AFTER THE SECOND VACCINE ONE

1001
00:34:57,120 --> 00:34:59,200
WEEK AFTER THAT.

1002
00:34:59,200 --> 00:35:01,240
BUT AGAIN THOSE INDIVIDUALS WHO

1003
00:35:01,240 --> 00:35:02,840
HAD ONLY BEEN VACCINATED AND

1004
00:35:02,840 --> 00:35:06,640
HADN'T HAD A PREVIOUS INFECTION

1005
00:35:06,640 --> 00:35:07,640
QUICKLY GAIN SIMILAR NUMBERS TO

1006
00:35:07,640 --> 00:35:08,920
THE INDIVIDUALS WHO HAVE BEEN

1007
00:35:08,920 --> 00:35:10,440
PREVIOUSLY INFECTED AND AGAIN WE

1008
00:35:10,440 --> 00:35:11,640
DIDN'T SEE A BOOST MANY THE

1009
00:35:11,640 --> 00:35:13,040
MEMORY RESPONSE OF THOSE THAT

1010
00:35:13,040 --> 00:35:14,960
HAD BEEN PREVIOUSLY INFECTED AND

1011
00:35:14,960 --> 00:35:18,760
AT THIS POINT IN THOSE WHO WERE

1012
00:35:18,760 --> 00:35:19,720
INFECTIOUS NAIVE EITHER.

1013
00:35:19,720 --> 00:35:22,040
AND LASTLY, ONE OF THE REALLY

1014
00:35:22,040 --> 00:35:23,120
MOST IMPORTANT THINGS WE CAN

1015
00:35:23,120 --> 00:35:27,000
LOOK AT WAS HOW DO THESE

1016
00:35:27,000 --> 00:35:28,160
ANTIBODIES FROM THESE

1017
00:35:28,160 --> 00:35:30,960
INDIVIDUALS FROM THEIR PLASMA

1018
00:35:30,960 --> 00:35:32,240
FUNCTION TO RESPOND TO EITHER

1019
00:35:32,240 --> 00:35:36,880
THE DELTA VARIANT OR OMICRON

1020
00:35:36,880 --> 00:35:38,120
VARIANT CONSIDERING THESE WERE

1021
00:35:38,120 --> 00:35:40,800
ALL INDIVIDUALS THAT WERE

1022
00:35:40,800 --> 00:35:42,120
IMMUNIZED OR INFECTED WITH THE

1023
00:35:42,120 --> 00:35:44,520
SPIKE PROTEIN FROM THE WUHAN

1024
00:35:44,520 --> 00:35:45,040
STRAIN.

1025
00:35:45,040 --> 00:35:46,880
SO WHEN WE LOOK AT THIS, AGAIN

1026
00:35:46,880 --> 00:35:48,120
RED IS PEOPLE WHO HAVE BEEN

1027
00:35:48,120 --> 00:35:50,440
PREVIOUSLY INFECTED, BLUE ARE

1028
00:35:50,440 --> 00:35:52,240
THE NAIVE INDIVIDUALS AND WHAT

1029
00:35:52,240 --> 00:35:55,480
YOU CAN SEE IS THAT IF WE ARE

1030
00:35:55,480 --> 00:35:58,440
LOOKING SIX MONTHS POST VACCINE

1031
00:35:58,440 --> 00:35:59,840
TO IN INDIVIDUALS WHO HAD NEVER

1032
00:35:59,840 --> 00:36:01,840
HAD INFECTION, THEY VERY MUCH

1033
00:36:01,840 --> 00:36:04,720
LOST A LOT OF THEIR ABILITY TO

1034
00:36:04,720 --> 00:36:06,560
NEUTRALIZE SARS COV-2 AND THIS

1035
00:36:06,560 --> 00:36:09,720
IS IN OUR BSL 3 USING INFECTION

1036
00:36:09,720 --> 00:36:12,360
BLOCKING INFECTION OF VIR ROW

1037
00:36:12,360 --> 00:36:13,640
CELLS BUT ONCE THE INDIVIDUALS

1038
00:36:13,640 --> 00:36:15,600
ARE BOOSTED THEY REGAIN THAT

1039
00:36:15,600 --> 00:36:19,680
ABILITY TO NEUTRALIZE DELTA.

1040
00:36:19,680 --> 00:36:20,240
INTERESTINGLY PEOPLE WHO

1041
00:36:20,240 --> 00:36:21,640
PREVIOUSLY INFECTED STILL HAVE

1042
00:36:21,640 --> 00:36:23,880
THAT ABILITY AT SIX MONTHS POST

1043
00:36:23,880 --> 00:36:25,760
VACCINE TWO, AND IT IS NOT

1044
00:36:25,760 --> 00:36:29,560
ENHANCED SIGNIFICANTLY BY THE

1045
00:36:29,560 --> 00:36:32,120
BOOST.

1046
00:36:32,120 --> 00:36:34,240
THAT IS SHOWN NUMERICALLY HERE.

1047
00:36:34,240 --> 00:36:36,120
LOOKING AT OMICRON VARIANT WE

1048
00:36:36,120 --> 00:36:38,240
SEE A SIMILAR PATTERN, THIS WAS

1049
00:36:38,240 --> 00:36:40,080
REASSURING TO US INDIVIDUALS WHO

1050
00:36:40,080 --> 00:36:42,680
HAVE THIS HYBRID IMMUNITY

1051
00:36:42,680 --> 00:36:44,320
PREVIOUSLY INFECTED AND THEN

1052
00:36:44,320 --> 00:36:46,800
VACCINATED ARE STILL CAPABLE OF

1053
00:36:46,800 --> 00:36:48,640
NEUTRALIZING LARGELY

1054
00:36:48,640 --> 00:36:49,920
NEUTRALIZING OMICRON, THE BOOST

1055
00:36:49,920 --> 00:36:51,160
DOESN'T MAKE A SIGNIFICANT

1056
00:36:51,160 --> 00:36:52,520
DIFFERENCE IN THAT.

1057
00:36:52,520 --> 00:36:55,760
BUT THOSE INDIVIDUALS WHO HAD

1058
00:36:55,760 --> 00:36:57,840
ONLY BEEN VACCINATED HAVE A

1059
00:36:57,840 --> 00:36:59,200
LOWER ABILITY TO NEUTRALIZE

1060
00:36:59,200 --> 00:37:03,200
OMICRON THAN AGAIN AS BOOSTED BY

1061
00:37:03,200 --> 00:37:04,960
THE INCREASE ANTIBODY TITER THAT

1062
00:37:04,960 --> 00:37:07,200
WE SAW PREVIOUSLY.

1063
00:37:07,200 --> 00:37:09,440
SO THAT WAS REASSURING.

1064
00:37:09,440 --> 00:37:12,080
SO THE THIRD VAX OR BOOST NAIVE

1065
00:37:12,080 --> 00:37:13,240
INDIVIDUALS CAN NORMALIZE

1066
00:37:13,240 --> 00:37:15,040
DIFFERENCES IN THE QUANTITIES OF

1067
00:37:15,040 --> 00:37:17,280
THESE RBD SPECIFIC MEMORY B

1068
00:37:17,280 --> 00:37:19,160
CELLS SEEN EARLIER TIME POINTS

1069
00:37:19,160 --> 00:37:20,560
BUT IN DATA I DIDN'T SHOW TODAY

1070
00:37:20,560 --> 00:37:22,520
THESE PREVIOUSLY INFECTED

1071
00:37:22,520 --> 00:37:23,840
INDIVIDUALS DO RETAIN

1072
00:37:23,840 --> 00:37:25,760
CHARACTERISTICS THAT ARE NOT

1073
00:37:25,760 --> 00:37:27,840
SEEN IN THE VACCINATED

1074
00:37:27,840 --> 00:37:30,720
INDIVIDUALS, AT TIME POINTS POST

1075
00:37:30,720 --> 00:37:32,000
VACCINE TWO.

1076
00:37:32,000 --> 00:37:33,640
THEY RETAIN QUALITY THAT LOOKS

1077
00:37:33,640 --> 00:37:35,600
MORE ACTIVATED, THEY HAVE MORE

1078
00:37:35,600 --> 00:37:37,640
CLASSICAL IGG MEMORY B CELLS BUT

1079
00:37:37,640 --> 00:37:39,360
AGAIN THIS IS NORMALIZED BY THAT

1080
00:37:39,360 --> 00:37:39,840
BOOST.

1081
00:37:39,840 --> 00:37:41,920
SO AGAIN, GETTING TO ROSS'S

1082
00:37:41,920 --> 00:37:44,120
QUESTION, SOME OF THESE

1083
00:37:44,120 --> 00:37:46,440
DIFFERENCES CAN BE NORMALIZE BY

1084
00:37:46,440 --> 00:37:50,200
A THIRD DOSE OF ANTIGEN BUT

1085
00:37:50,200 --> 00:37:51,800
THESE PREVIOUSLY INFECTED

1086
00:37:51,800 --> 00:37:53,680
INDIVIDUALS ARE BETTER ABLE TO

1087
00:37:53,680 --> 00:37:54,960
NEUTRALIZE VARIANTS INCLUDING

1088
00:37:54,960 --> 00:37:58,040
OMICRON THAN NAIVE INDIVIDUALS

1089
00:37:58,040 --> 00:38:00,640
AT SIX MONTHS POST VACCINE TWO,

1090
00:38:00,640 --> 00:38:01,800
SUGGESTING HIGH QUALITY LONG

1091
00:38:01,800 --> 00:38:03,560
LIVED PLASMA CELLS THAT ARE

1092
00:38:03,560 --> 00:38:04,600
PERSISTING IN THESE INDIVIDUALS

1093
00:38:04,600 --> 00:38:06,280
AND THAT MAY ALSO SPEAK TO THAT

1094
00:38:06,280 --> 00:38:09,400
QUESTION OF WHY DO YOU LOSE SOME

1095
00:38:09,400 --> 00:38:14,400
OF THE ONLY I DON'T KNOW

1096
00:38:14,400 --> 00:38:16,440
NEUTRALIZATION CAPACITY THAT

1097
00:38:16,440 --> 00:38:17,800
THAT QUESTION SHANE PRESENTED

1098
00:38:17,800 --> 00:38:20,960
AND I CAN TALK ABOUT THAT LATER.

1099
00:38:20,960 --> 00:38:24,080
LASTLY WE ALSO LOOKED AT THE CD4

1100
00:38:24,080 --> 00:38:25,960
T-CELLS BECAUSE WE KNOW CD4

1101
00:38:25,960 --> 00:38:28,880
T-CELLS ARE NOT ONLY REALLY

1102
00:38:28,880 --> 00:38:30,440
IMPORTANT CELLS FOR REACTIVATING

1103
00:38:30,440 --> 00:38:35,040
MEMORY B CELLS BUT ALSO FOR

1104
00:38:35,040 --> 00:38:36,040
EXPRESSING DIFFERENT CYTOKINES

1105
00:38:36,040 --> 00:38:38,120
THAT ACTIVATE INNATE CELLS TO

1106
00:38:38,120 --> 00:38:38,840
KILL THE VIRUS.

1107
00:38:38,840 --> 00:38:41,480
WE DID THIS USING DIFFERENT AIM

1108
00:38:41,480 --> 00:38:44,600
ASSAYS WE FIRST LOOKED FOR A

1109
00:38:44,600 --> 00:38:46,800
PEPTIDE POOL THAT WAS DERIVED

1110
00:38:46,800 --> 00:38:48,400
FROM PROTEINS IN THE VIRAL

1111
00:38:48,400 --> 00:38:48,880
INFECTION.

1112
00:38:48,880 --> 00:38:51,240
BUT NOT IN THE VACCINATION.

1113
00:38:51,240 --> 00:38:53,240
THESE MN POOLS HERE.

1114
00:38:53,240 --> 00:38:56,240
WE ALSO LOOKED AT THE SPIKE

1115
00:38:56,240 --> 00:39:00,880
SPECIFIC RESPONSES IN OUR NAIVE

1116
00:39:00,880 --> 00:39:02,640
INFECTION INDIVIDUALS PREVIOUSLY

1117
00:39:02,640 --> 00:39:03,320
INFECTED INDIVIDUALS.

1118
00:39:03,320 --> 00:39:06,360
WHAT YOU SEE IS THE M AND N

1119
00:39:06,360 --> 00:39:07,000
SPECIFIC RESPONSES ARE ONLY

1120
00:39:07,000 --> 00:39:11,040
VISIBLE IN PEOPLE WHO HAD HAD

1121
00:39:11,040 --> 00:39:12,200
PREVIOUS INFECTION TO LARGE

1122
00:39:12,200 --> 00:39:15,840
DEGREE, THOSE ARE STATIC OVER

1123
00:39:15,840 --> 00:39:18,480
VACCINATION SO THERE IS NO

1124
00:39:18,480 --> 00:39:20,280
DETRACTION TO THE RESPONSE FROM

1125
00:39:20,280 --> 00:39:21,680
THIS VACCINE THAT DOESN'T

1126
00:39:21,680 --> 00:39:24,360
CONTAIN THE M AND N PROTEINS

1127
00:39:24,360 --> 00:39:25,560
THAT STAY STATIC THROUGHOUT

1128
00:39:25,560 --> 00:39:26,880
EVERYTHING WE LOOK AT.

1129
00:39:26,880 --> 00:39:29,120
BUT YOU CAN ALSO NICELY SEE

1130
00:39:29,120 --> 00:39:30,240
INDUCTION OF SPIKE RESPONSE IN

1131
00:39:30,240 --> 00:39:32,400
PREVIOUSLY NAIVE INDIVIDUALS,

1132
00:39:32,400 --> 00:39:34,960
AND THE EXPANSION OF THAT

1133
00:39:34,960 --> 00:39:36,760
RESPONSE IN THE PREVIOUSLY

1134
00:39:36,760 --> 00:39:37,640
INFECTED INDIVIDUALS AFTER

1135
00:39:37,640 --> 00:39:38,800
VACCINATION.

1136
00:39:38,800 --> 00:39:41,040
THAT IS MAPPED OUT HERE YOU CAN

1137
00:39:41,040 --> 00:39:43,520
TRACK THIS OVER TIME.

1138
00:39:43,520 --> 00:39:48,000
AND WHAT YOU CAN SEE IS THE

1139
00:39:48,000 --> 00:39:50,720
T-CELL MEMORY OF THE M AND N

1140
00:39:50,720 --> 00:39:53,920
POOL MEANS HIGHER IN PEOPLE IN

1141
00:39:53,920 --> 00:39:55,400
PREVIOUSLY INFECTED THAN THOSE

1142
00:39:55,400 --> 00:39:56,680
NEVER INFECTED AS ONE WAY TO

1143
00:39:56,680 --> 00:39:58,680
EXPECT BUT LOOK AT THE SPIKE

1144
00:39:58,680 --> 00:40:01,440
SPECIFIC RESPONSE, THE RESPONSE

1145
00:40:01,440 --> 00:40:02,680
TO SPIKES STARTS HIGHER IN

1146
00:40:02,680 --> 00:40:04,600
PREVIOUSLY INFECTED INDIVIDUALS

1147
00:40:04,600 --> 00:40:06,200
BUT IS QUICKLY CAUGHT UP BY THE

1148
00:40:06,200 --> 00:40:09,400
VACCINE AND THAT'S RETAINED AT

1149
00:40:09,400 --> 00:40:11,480
THAT POST VAX 3 TIME POINT AS

1150
00:40:11,480 --> 00:40:12,640
WELL.

1151
00:40:12,640 --> 00:40:14,160
LASTLY, THE QUALITY OF THE

1152
00:40:14,160 --> 00:40:15,360
T-CELL RESPONSES WAS REALLY

1153
00:40:15,360 --> 00:40:17,640
INTERESTING TO US, WE WANTED TO

1154
00:40:17,640 --> 00:40:20,640
KNOW IF T-CELL IS CD4 T-CELL HAD

1155
00:40:20,640 --> 00:40:24,680
SEEN INFECTION AS OPPOSED TO

1156
00:40:24,680 --> 00:40:26,240
SEEING A VACCINATION IN THE ARM,

1157
00:40:26,240 --> 00:40:28,080
THEY ADOPT DIFFERENT QUALITATIVE

1158
00:40:28,080 --> 00:40:29,240
ATTRIBUTES AND ONE OF THE WAYS

1159
00:40:29,240 --> 00:40:33,640
WE CAN LOOK AT THIS IS

1160
00:40:33,640 --> 00:40:35,000
DISSECTING THE CYTOKINES THESE

1161
00:40:35,000 --> 00:40:35,600
CELLS CAN MAKE.

1162
00:40:35,600 --> 00:40:39,840
THIS IS AGAIN LOOKING AT THE

1163
00:40:39,840 --> 00:40:41,840
VICTIMS NOT PREVIOUSLY INFECT

1164
00:40:41,840 --> 00:40:42,880
BUD VACCINATED.

1165
00:40:42,880 --> 00:40:46,240
VACCINATION INDUCES A NICE TH 1

1166
00:40:46,240 --> 00:40:49,840
RESPONSE AS PREVIOUSLY DESCRIBED

1167
00:40:49,840 --> 00:40:50,080
DESCRIBED.

1168
00:40:50,080 --> 00:40:51,240
THESE INDIVIDUALS PREVIOUSLY

1169
00:40:51,240 --> 00:40:55,680
INFECTED HOW FAR THERE IS A MUCH

1170
00:40:55,680 --> 00:40:57,880
BIGGER PERCENTAGE OF CD4 POOL

1171
00:40:57,880 --> 00:40:59,480
MAKING INTERFERON GAMMA, THAT

1172
00:40:59,480 --> 00:41:00,680
HELPS THROUGH FOR EVERY TIME

1173
00:41:00,680 --> 00:41:02,200
POINT THAT WE LOOK AT WHICH IS

1174
00:41:02,200 --> 00:41:04,280
JUST LOOKING AT HERE, IT IS

1175
00:41:04,280 --> 00:41:05,640
ALMOST EASIER TO SEE WITH LINES

1176
00:41:05,640 --> 00:41:07,520
HERE SO FOR EVERY TIME POINT WE

1177
00:41:07,520 --> 00:41:09,400
LOOK THERE WAS HIGHER PROPORTION

1178
00:41:09,400 --> 00:41:11,040
OF INTERFERON GAMMA POSITIVE

1179
00:41:11,040 --> 00:41:13,080
CELLS IF YOU HAD PRIOR INFECTION

1180
00:41:13,080 --> 00:41:15,120
SO EVEN ADDITIONAL ANTIGEN DOSES

1181
00:41:15,120 --> 00:41:21,040
COULDN'T ALTER THE DIFFERENCE,

1182
00:41:21,040 --> 00:41:22,200
SUGGESTING IMPRINTING FROM THE

1183
00:41:22,200 --> 00:41:22,800
PRIOR INFECTION.

1184
00:41:22,800 --> 00:41:25,000
WE SAW SIMILAR PATTERNS WHEN WE

1185
00:41:25,000 --> 00:41:28,400
LOOK AT IL 10 PRODUCTION WE SAW

1186
00:41:28,400 --> 00:41:30,640
MORE IL 10 PRODUCTION IN THE

1187
00:41:30,640 --> 00:41:31,880
SUPPRESSIVE CYTOKINE IN

1188
00:41:31,880 --> 00:41:34,320
INDIVIDUALS PREVIOUSLY INFECTED

1189
00:41:34,320 --> 00:41:35,960
VERSUS THOSE VACCINATED AND TOO

1190
00:41:35,960 --> 00:41:38,560
WAS RETAINED A AT ALL TIME

1191
00:41:38,560 --> 00:41:39,000
POINTSES.

1192
00:41:39,000 --> 00:41:41,160
SO THIS IS JUST A QUANTIFY WHAT

1193
00:41:41,160 --> 00:41:44,000
I JUST TOLD YOU, M AND N

1194
00:41:44,000 --> 00:41:45,960
RESPONSES REMAIN STATIC BUT THE

1195
00:41:45,960 --> 00:41:47,920
QUANTITY OF CD4 T-CELLS ARE

1196
00:41:47,920 --> 00:41:49,160
NORMALIZED BY THE VACCINE BY THE

1197
00:41:49,160 --> 00:41:51,760
NUMBER OF ANTIGEN DOSES.

1198
00:41:51,760 --> 00:41:53,080
BUT THERE ARE CHARACTERISTICS

1199
00:41:53,080 --> 00:41:56,080
HERE THAT ARE NOT TOTALLY

1200
00:41:56,080 --> 00:42:00,640
NORMALIZED AND JUST IN TOTAL

1201
00:42:00,640 --> 00:42:02,520
CONCLUSION, THE mRNA VACCINES

1202
00:42:02,520 --> 00:42:04,840
ARE REALLY QUITE REMARKABLE AT

1203
00:42:04,840 --> 00:42:07,040
INDUCING VERY SIMILAR TH 1 TYPES

1204
00:42:07,040 --> 00:42:09,040
OF ANTIVIRAL RESPONSES, AND WE

1205
00:42:09,040 --> 00:42:13,040
OBVIOUSLY KNOW THEY INDUCE GREAT

1206
00:42:13,040 --> 00:42:14,240
PROTECTION.

1207
00:42:14,240 --> 00:42:15,440
MANY OF THE DIFFERENCES THAT WE

1208
00:42:15,440 --> 00:42:20,680
SAW BETWEEN PREVIOUSLY INFECTED

1209
00:42:20,680 --> 00:42:24,440
AND VACCINE ONLY INDIVIDUALS

1210
00:42:24,440 --> 00:42:26,040
WERE AMELIORATED BY THIRD DOSE

1211
00:42:26,040 --> 00:42:27,240
VACCINE BUT THERE WERE QUALITIES

1212
00:42:27,240 --> 00:42:28,800
TRULY IMPRINTED BY THAT PREVIOUS

1213
00:42:28,800 --> 00:42:30,840
INFECTION INCLUDING CYTOKINE

1214
00:42:30,840 --> 00:42:32,160
PRODUCTION BY T-CELLS AND SOME

1215
00:42:32,160 --> 00:42:33,600
OF THE QUALITIES WE THINK IN THE

1216
00:42:33,600 --> 00:42:34,760
BREADTH OF THE MEMORY B CELLS

1217
00:42:34,760 --> 00:42:38,760
THAT I DIDN'T GET INTO TODAY.

1218
00:42:38,760 --> 00:42:39,760
LASTLY IT IS IMPORTANT TO POINT

1219
00:42:39,760 --> 00:42:41,120
OUT ONCE THE HIGH LEVELS

1220
00:42:41,120 --> 00:42:44,600
IMMUNITY ARE REACHED, ADDITIONAL

1221
00:42:44,600 --> 00:42:46,000
HOMOLOGOUS BOOST MAY HAVE

1222
00:42:46,000 --> 00:42:47,840
LIMITING RETURNS, WE DIDN'T SEE

1223
00:42:47,840 --> 00:42:49,800
MUCH BOOST IN RESPONSE IN THE

1224
00:42:49,800 --> 00:42:51,120
PREVIOUSLY INFECTED VACCINATED

1225
00:42:51,120 --> 00:42:53,480
INDIVIDUALS.

1226
00:42:53,480 --> 00:42:56,520
WITH THAT I'LL THANK THE PEOPLE

1227
00:42:56,520 --> 00:42:58,440
WHO DID THIS AND HAPPY TO TAKE

1228
00:42:58,440 --> 00:43:01,480
ANY QUESTIONS.

1229
00:43:01,480 --> 00:43:03,960
>> THANK YOU, MARION.

1230
00:43:03,960 --> 00:43:05,280
SO WE ARE RUNNING A LITTLE LOW

1231
00:43:05,280 --> 00:43:06,840
ON TIME SO IF YOU HAVE A

1232
00:43:06,840 --> 00:43:13,680
QUESTION PLEASE RAISE YOUR HAND.

1233
00:43:13,680 --> 00:43:15,440
WERE YOU ABLE TO STRATIFY THIS

1234
00:43:15,440 --> 00:43:18,240
BY SEVERITY OF INFECTION?

1235
00:43:18,240 --> 00:43:20,440
ANY PREVIOUSLY INFECTED COHORT

1236
00:43:20,440 --> 00:43:22,080
LIKE SEVERE GROUP HOSPITALIZED

1237
00:43:22,080 --> 00:43:23,520
THEN GOT BETTER?

1238
00:43:23,520 --> 00:43:25,240
>> EVERYONE THAT WE WERE LOOKING

1239
00:43:25,240 --> 00:43:27,640
AGENT FOR THESE STUDIES HAD MILD

1240
00:43:27,640 --> 00:43:29,240
INFECTION SO WE WEREN'T ABLE TO

1241
00:43:29,240 --> 00:43:30,640
DO THAT IN THESE STUDIES.

1242
00:43:30,640 --> 00:43:32,840
BUT I THINK IT WOULD BE REALLY

1243
00:43:32,840 --> 00:43:34,800
INTERESTING ESPECIALLY WITH IL

1244
00:43:34,800 --> 00:43:39,480
10 PRODUCTION TO SEE HOW THAT

1245
00:43:39,480 --> 00:43:39,720
CHANGES.

1246
00:43:39,720 --> 00:43:42,040
>> ANY OTHER QUESTIONS?

1247
00:43:42,040 --> 00:43:44,240
THEN WE'LL HAVE OPPORTUNITY AT

1248
00:43:44,240 --> 00:43:46,880
END AS WELL TO DISCUSS THIS

1249
00:43:46,880 --> 00:43:47,280
DATA.

1250
00:43:47,280 --> 00:43:50,120
SO WHY DON'T WE MOVE ON THEN TO

1251
00:43:50,120 --> 00:43:53,720
THE NEXT SPEAKER.

1252
00:43:53,720 --> 00:43:56,960
IS DAVID FREEMAN, DO YOU WANT TO

1253
00:43:56,960 --> 00:44:03,200
STOP SHARING?

1254
00:44:03,200 --> 00:44:03,880
MAYBE WE HAVEN'T.

1255
00:44:03,880 --> 00:44:07,560
THE NEXT SPEAKER IS DAVID

1256
00:44:07,560 --> 00:44:08,240
FREEMONT, WASHINGTON UNIVERSITY

1257
00:44:08,240 --> 00:44:09,520
ST. LOUIS WHO WILL SPEAK

1258
00:44:09,520 --> 00:44:11,400
LANDSCAPE OF ANTIBODY RESPONSES

1259
00:44:11,400 --> 00:44:17,160
TO SARS COV-2 INFECTION.

1260
00:44:17,160 --> 00:44:18,960
GET THOSE SLIDES UP.

1261
00:44:18,960 --> 00:44:19,680
>> YES.

1262
00:44:19,680 --> 00:44:21,240
ARE MY SLIDES UP?

1263
00:44:21,240 --> 00:44:24,080
>> WE CAN SEE THEM.

1264
00:44:24,080 --> 00:44:26,760
>> THERE'S BEEN A LOT OF

1265
00:44:26,760 --> 00:44:28,240
MOVEMENT AND DIFFERENT

1266
00:44:28,240 --> 00:44:31,760
DISCIPLINES OBVIOUSLY TO DEAL

1267
00:44:31,760 --> 00:44:33,000
WITH COVID PANDEMIC.

1268
00:44:33,000 --> 00:44:34,080
ONE OF THE THINGS THAT I HAVE

1269
00:44:34,080 --> 00:44:35,840
BEEN PARTICIPATING IN THAT I

1270
00:44:35,840 --> 00:44:38,640
THINK HAS BEEN QUITE SUCCESSFUL

1271
00:44:38,640 --> 00:44:40,520
IS STRUCTURAL GENOMICS FOCUSED

1272
00:44:40,520 --> 00:44:43,800
ISSUES WITH LOOKING AT THE MANY

1273
00:44:43,800 --> 00:44:49,080
PROTEINS ENCODED BY SARS COV-2.

1274
00:44:49,080 --> 00:44:51,080
I WANT TO HIGHLIGHT WORK,

1275
00:44:51,080 --> 00:44:52,200
CONTRACT WORK THROUGH CENTER FOR

1276
00:44:52,200 --> 00:44:53,440
STRUCTURAL GENOMICS AND

1277
00:44:53,440 --> 00:44:55,560
INFECTIOUS DISEASE BASED AT

1278
00:44:55,560 --> 00:44:56,440
NORTHWESTERN UNIVERSITY CHICAGO

1279
00:44:56,440 --> 00:44:57,960
THAT I HAVE BEEN PART OF FOR 15

1280
00:44:57,960 --> 00:44:59,880
YEARS NOW.

1281
00:44:59,880 --> 00:45:00,960
THERE IS HUNDRED STRUCTURE

1282
00:45:00,960 --> 00:45:02,880
DEPOSITED IN THE PROTEIN DATA

1283
00:45:02,880 --> 00:45:05,240
BANK OF VARIOUS FULL LENGTH OR

1284
00:45:05,240 --> 00:45:09,240
FRAGMENTS OF VARIOUS COVID

1285
00:45:09,240 --> 00:45:11,040
PROTEINS AND IT'S BEEN A VERY

1286
00:45:11,040 --> 00:45:11,800
SUCCESSFUL ENTERPRISE.

1287
00:45:11,800 --> 00:45:14,080
MY WORK IS FOCUSED ONLY SOME OF

1288
00:45:14,080 --> 00:45:19,280
THE ACCESSORY PROTEINS THAT 7, 8

1289
00:45:19,280 --> 00:45:21,040
AS WELL AS SPIKE COMPLEXES WITH

1290
00:45:21,040 --> 00:45:22,520
ANTIBODIES AS I'M GOING TO TALK

1291
00:45:22,520 --> 00:45:26,760
ABOUT TODAY.

1292
00:45:26,760 --> 00:45:29,240
SO MANY OF YOU KNOW THIS, THE

1293
00:45:29,240 --> 00:45:35,040
TRIAL RICK SPIKE HAS TWO MAJOR

1294
00:45:35,040 --> 00:45:36,480
AREAS ANTIBODIES HAVE FOUND TO

1295
00:45:36,480 --> 00:45:39,080
BE NEUTRALIZING OR PROTECTIVE.

1296
00:45:39,080 --> 00:45:40,760
THE RECEPTOR BINDING DOMAIN

1297
00:45:40,760 --> 00:45:42,360
WHERE YOU CAN HAVE ANTIBODIES

1298
00:45:42,360 --> 00:45:45,040
THAT BIND DIRECTLY AT THE ACE 2

1299
00:45:45,040 --> 00:45:48,080
SITE OR THERE ARE SOME EPITOPES

1300
00:45:48,080 --> 00:45:49,800
SHOWN TO BE NEUTRALIZING AND

1301
00:45:49,800 --> 00:45:52,240
PROTECTIVE OUTSIDE OF THE ACE 2

1302
00:45:52,240 --> 00:45:54,000
SITE AND RBD AN COLLECTION

1303
00:45:54,000 --> 00:45:56,760
ANTIBODIES FOCUSED ON THE MTD.

1304
00:45:56,760 --> 00:45:58,840
SO THIS POINT THOSE ARE THE TWO

1305
00:45:58,840 --> 00:46:05,800
MAJOR AREAS OF EPITOPES WE KNOW

1306
00:46:05,800 --> 00:46:06,920
PROTECTION PREVAIL.

1307
00:46:06,920 --> 00:46:08,560
REMINDING YOU TOO, THIS IS NOT A

1308
00:46:08,560 --> 00:46:12,240
STATIC PROTEIN BUT ONE THAT HAS

1309
00:46:12,240 --> 00:46:16,000
CONFIRMATIONAL VARIATION IN

1310
00:46:16,000 --> 00:46:17,440
PARTICULAR RECEPTOR BINDING

1311
00:46:17,440 --> 00:46:18,840
DOMAINS NEEDS TO BE

1312
00:46:18,840 --> 00:46:20,280
CONFIGURATION TO BIND ACE 2 AND

1313
00:46:20,280 --> 00:46:22,280
WHAT WE LEARNED ALMOST TWO YEARS

1314
00:46:22,280 --> 00:46:25,600
NOW ANTIBODY CONSIST RECOGNIZE

1315
00:46:25,600 --> 00:46:27,040
THIS RECEPTOR BINDING DOMAIN IN

1316
00:46:27,040 --> 00:46:28,880
UP OR DOWN CONFIGURATION.

1317
00:46:28,880 --> 00:46:31,720
SO WE STARTED OUR WORK EARLY ON

1318
00:46:31,720 --> 00:46:35,200
THE COLLABORATION WITH

1319
00:46:35,200 --> 00:46:36,840
(INDISCERNIBLE) AT WASU WHO

1320
00:46:36,840 --> 00:46:39,920
DEVELOPED A PANEL OF MONOCLONAL

1321
00:46:39,920 --> 00:46:41,440
ANTIBODIES WE HELPED TO DEVELOP

1322
00:46:41,440 --> 00:46:42,080
AND CHARACTERIZE.

1323
00:46:42,080 --> 00:46:43,560
WE FOUND TWO IN PARTICULAR WHICH

1324
00:46:43,560 --> 00:46:45,840
WERE PARTICULARLY POTENT BOTH IN

1325
00:46:45,840 --> 00:46:49,560
VIVO AND IN VITRO AT

1326
00:46:49,560 --> 00:46:51,240
NEUTRALIZING THE INITIAL WUHAN

1327
00:46:51,240 --> 00:46:52,280
STRAIN OF THE VIRUS.

1328
00:46:52,280 --> 00:46:56,840
WE PROCEEDED TO DO MICROSCOPY

1329
00:46:56,840 --> 00:46:57,840
RECONSTRUCTIONS WITH THESE TWO

1330
00:46:57,840 --> 00:46:59,600
MORE POTENTLY NEUTRALIZING

1331
00:46:59,600 --> 00:47:01,400
ANTIBODIES BOUND TO THE TRIAL

1332
00:47:01,400 --> 00:47:02,960
RICK SPIKE.

1333
00:47:02,960 --> 00:47:06,040
AND AS OTHERS OBSERVED WHAT WE

1334
00:47:06,040 --> 00:47:08,920
FIND IS THAT THE ANTIBODIES BIND

1335
00:47:08,920 --> 00:47:11,840
IN UP OR DOWN CONFIGURATION FOR

1336
00:47:11,840 --> 00:47:15,240
OUR POPULATION ROUGHLY, ABOUT

1337
00:47:15,240 --> 00:47:18,360
155050 SO WE CAN HAVE STRUCTURES

1338
00:47:18,360 --> 00:47:19,720
WHICH ARE ALL THE WAY DOWN, YOU

1339
00:47:19,720 --> 00:47:20,800
CAN HAVE STRUCTURE WHICH ARE

1340
00:47:20,800 --> 00:47:22,640
MIXTURES OF UP AND DOWN.

1341
00:47:22,640 --> 00:47:24,320
WE THINK THIS IS QUITE

1342
00:47:24,320 --> 00:47:25,040
FUNCTIONALLY IMPORTANT BECAUSE

1343
00:47:25,040 --> 00:47:27,640
AGAIN THE RBD NEEDS TO COME UP

1344
00:47:27,640 --> 00:47:29,600
IN OTHER WORDS TO ENGAGE ACE 2

1345
00:47:29,600 --> 00:47:34,520
SO ANTIBODIES THAT CAN KEEP ALL

1346
00:47:34,520 --> 00:47:36,600
THE RECEPTOR BINDING DOMAINS IN

1347
00:47:36,600 --> 00:47:38,320
DOWN CONFIGURATION WILL BLOCK

1348
00:47:38,320 --> 00:47:41,640
ABILITY TO ENGAGE WITH ACE 2

1349
00:47:41,640 --> 00:47:42,320
RECEPTOR.

1350
00:47:42,320 --> 00:47:43,920
SO IF WE LOOK MORE DETAIL ABOUT

1351
00:47:43,920 --> 00:47:46,160
THE EPITOPES ENGAGED BY TWO

1352
00:47:46,160 --> 00:47:50,280
NEUTRALIZING ANTIBODY, 2 BL 4

1353
00:47:50,280 --> 00:47:52,760
AND HL 4 DON'T COMPETE WITH ONE

1354
00:47:52,760 --> 00:47:53,680
ANOTHER WE FIND SOME OF THE

1355
00:47:53,680 --> 00:47:54,760
THINGS ON BOTH OF THEM.

1356
00:47:54,760 --> 00:47:56,120
ONE HOWEVER HITS RECEPTOR

1357
00:47:56,120 --> 00:47:57,640
BINDING MOTIF WHILE THE OTHER IS

1358
00:47:57,640 --> 00:47:58,960
ADJACENT TO THAT RECEPTOR

1359
00:47:58,960 --> 00:48:00,000
BINDING MOTIF.

1360
00:48:00,000 --> 00:48:02,080
SO IF WE COMPARE THE ONE THAT

1361
00:48:02,080 --> 00:48:03,440
DOES IN FACT BIND WHAT WE CALL

1362
00:48:03,440 --> 00:48:05,360
RECEPTOR BINDING MOTIF, WHICH IS

1363
00:48:05,360 --> 00:48:06,840
ESSENTIALLY A ELONGATED LOOP,

1364
00:48:06,840 --> 00:48:12,160
WHICH IS WHAT IS ENGAGING ACE 2,

1365
00:48:12,160 --> 00:48:14,040
THESE ARE MOUSE DERIVED

1366
00:48:14,040 --> 00:48:15,400
MONOCLONALS THEY HAVE VERY

1367
00:48:15,400 --> 00:48:19,440
SIMILAR EPITOPE TO ANTIBODIES

1368
00:48:19,440 --> 00:48:20,280
WHICH REASON OBJECTIFIED FROM

1369
00:48:20,280 --> 00:48:21,840
HUMANS.

1370
00:48:21,840 --> 00:48:23,280
THESE HUMAN ANTIBODIES ARE

1371
00:48:23,280 --> 00:48:24,440
GROUPED TO DIFFERENT CATEGORIES

1372
00:48:24,440 --> 00:48:25,880
ESSENTIALLY BASED ON BINDING

1373
00:48:25,880 --> 00:48:27,600
ORIENTATION OR ANGLE, THE WAY

1374
00:48:27,600 --> 00:48:29,480
THEY ENGAGE RECEPTOR BINDING

1375
00:48:29,480 --> 00:48:30,840
MOTIF ITSELF.

1376
00:48:30,840 --> 00:48:32,840
BUT THEY ALL SHARE THE CAPACITY

1377
00:48:32,840 --> 00:48:34,480
OF POTENTLY DISRUPTING THE

1378
00:48:34,480 --> 00:48:35,600
INTERACTION OF THE RECEPTOR

1379
00:48:35,600 --> 00:48:41,080
BINDING DOMAIN.

1380
00:48:41,080 --> 00:48:43,360
WITH ACE 2, IF WE COMPARE ON THE

1381
00:48:43,360 --> 00:48:44,280
OTHER HAND OUTSIDE THE BINDING

1382
00:48:44,280 --> 00:48:47,680
RECENT TORR MOTIF THERE'S FEWER

1383
00:48:47,680 --> 00:48:48,720
CHARACTERIZED ANTIBODIES IN THIS

1384
00:48:48,720 --> 00:48:51,480
FAMILY, THE ONLY ONE THAT HAS

1385
00:48:51,480 --> 00:48:53,840
EMERGENCY USE AUTHORIZATION IS

1386
00:48:53,840 --> 00:48:57,280
STR 9 WHICH IS THE BRGSK

1387
00:48:57,280 --> 00:48:59,920
ANTIBODY, IT HAS OVERLAPPING

1388
00:48:59,920 --> 00:49:02,400
EPITOPE WITH -- WHICH WAS NOT

1389
00:49:02,400 --> 00:49:06,000
INFACT ANTIBODY RAISED AGAINST

1390
00:49:06,000 --> 00:49:08,880
SARS 2 BUT A PATIENT RECOVERING

1391
00:49:08,880 --> 00:49:10,760
FROM SARS 1.

1392
00:49:10,760 --> 00:49:13,840
AND AS WE KNOW IT IS IMPORTANT

1393
00:49:13,840 --> 00:49:14,840
ANTIBODY BECAUSE AS I WILL COME

1394
00:49:14,840 --> 00:49:17,120
BACK TO, IT IS THE ONLY ANTIBODY

1395
00:49:17,120 --> 00:49:19,400
WITH EMERGENCY USE AUTHORIZATION

1396
00:49:19,400 --> 00:49:22,400
THAT CONCURRENTLY CAN BE USED TO

1397
00:49:22,400 --> 00:49:28,000
NEUTRALIZE OMICRON.

1398
00:49:28,000 --> 00:49:32,080
SO I WANT TO POINT OUT

1399
00:49:32,080 --> 00:49:32,760
UNIVERSITIES IS A GREAT

1400
00:49:32,760 --> 00:49:34,320
ENVIRONMENT WITH COLLABORATIONS

1401
00:49:34,320 --> 00:49:34,560
WE HAVE.

1402
00:49:34,560 --> 00:49:36,560
WE HAVE BEEN WORKING WITH SEAN

1403
00:49:36,560 --> 00:49:39,040
WHELIN'S LAB WITH ESCAPE MAPPING

1404
00:49:39,040 --> 00:49:40,440
MUTATION AND ANTIBODIES AND

1405
00:49:40,440 --> 00:49:41,560
SHOWN HERE SOME OF THE EARLY

1406
00:49:41,560 --> 00:49:44,240
EMPERIMENTS WE DID TO DO EPITOPE

1407
00:49:44,240 --> 00:49:45,480
MAPPING WITH THESE PARTICULAR

1408
00:49:45,480 --> 00:49:47,480
ANTIBODIES AND WE FOUND A NUMBER

1409
00:49:47,480 --> 00:49:53,240
OF ESCAPE MUTANTS USING THE BSB

1410
00:49:53,240 --> 00:49:54,240
PSEUDOTYPE VIRUS AS MECHANISM

1411
00:49:54,240 --> 00:49:56,840
FOR GENERATING MUTANTS.

1412
00:49:56,840 --> 00:50:01,320
AND JUST CALL OUT FOR EXAMPLE,

1413
00:50:01,320 --> 00:50:03,160
THE ESCAPE MUTATIONS THAT

1414
00:50:03,160 --> 00:50:06,960
DISRUPT THE 2 B L 47 EPITOPE ONE

1415
00:50:06,960 --> 00:50:09,200
THAT CAME UP QUICKLY IS THE EK

1416
00:50:09,200 --> 00:50:10,800
44 MUTATION, THAT IS WHAT WE

1417
00:50:10,800 --> 00:50:13,640
KNOW TO BE ONE MAJOR DISRUPTERS

1418
00:50:13,640 --> 00:50:20,200
OF MANY ANTIBODIES, SO POINT

1419
00:50:20,200 --> 00:50:23,560
BEING MANY MUTATIONS WHEN ESCAPE

1420
00:50:23,560 --> 00:50:25,000
MUTATIONS ARE ABSOLUTELY MIRROR

1421
00:50:25,000 --> 00:50:27,240
WHAT WE SEE IN THE NATURAL

1422
00:50:27,240 --> 00:50:29,040
VARIANTS OF CONCERNS SO JUST

1423
00:50:29,040 --> 00:50:30,600
AGAIN LOOKING AT ANTIBODIES

1424
00:50:30,600 --> 00:50:32,840
WHERE WE FOUND ESCAPE MUTATIONS,

1425
00:50:32,840 --> 00:50:35,840
WE ACTUALLY FIND NUMBER OF COINS

1426
00:50:35,840 --> 00:50:44,720
DENT MUTATIONS IN THE DATABASE.

1427
00:50:44,720 --> 00:50:47,160
SO I WON'T GO THROUGH THE

1428
00:50:47,160 --> 00:50:49,840
DETAILS BUT WE DID A NUMBER OF

1429
00:50:49,840 --> 00:50:51,520
EXPERIMENTS TO APPRECIATE THE

1430
00:50:51,520 --> 00:50:53,040
MECHANISMS OF NEUTRALIZATION.

1431
00:50:53,040 --> 00:50:57,480
WE KNOW PHYSICALLY THAT 2 BL 4

1432
00:50:57,480 --> 00:51:00,400
POTENTLY BLOCKS PHASE 2 BINDING

1433
00:51:00,400 --> 00:51:01,920
BUT 2 HL 4 DOES NOT.

1434
00:51:01,920 --> 00:51:04,600
HOWEVER WE WERE ABLE TO SHOW 2

1435
00:51:04,600 --> 00:51:07,000
HL 4 HAS CAPACITY OF DISRUPTION

1436
00:51:07,000 --> 00:51:09,440
OF ADHERENCE OF THE VIRUS

1437
00:51:09,440 --> 00:51:11,440
PRESUMABLY ONCE THE VIRUS NEEDS

1438
00:51:11,440 --> 00:51:13,040
TO ADHERE EXPOSES RECEPTOR

1439
00:51:13,040 --> 00:51:14,360
BINDING DOMAIN AND THEN IT CAN

1440
00:51:14,360 --> 00:51:17,400
ENGAGE THE ACE 2 SO OUR

1441
00:51:17,400 --> 00:51:19,760
PREFERRED MECHANISM OF ACTION IS

1442
00:51:19,760 --> 00:51:22,040
2 HL 4 ACTUAL MECHANISMS

1443
00:51:22,040 --> 00:51:25,240
DOMINANTLY TO STOP VIRAL

1444
00:51:25,240 --> 00:51:26,600
ADHERENCE WE STICK LATED BASED

1445
00:51:26,600 --> 00:51:28,200
ON BINDING SITE AND OTHER

1446
00:51:28,200 --> 00:51:29,480
PEOPLE'S ANALYSIS THAT THIS

1447
00:51:29,480 --> 00:51:31,880
MIGHT BE BECAUSE WE ARE

1448
00:51:31,880 --> 00:51:33,640
DISRUPTING GAG INTERACTION.

1449
00:51:33,640 --> 00:51:37,880
OR SULFATE CARBOHYDRATE

1450
00:51:37,880 --> 00:51:38,640
INTERACTION THOUGH WE WERE NEVER

1451
00:51:38,640 --> 00:51:40,560
ABLE TO PROVE AS MECHANISM FOR 2

1452
00:51:40,560 --> 00:51:44,400
HL 4, SO IT IS CLEAR 2 HL 4 HAS

1453
00:51:44,400 --> 00:51:45,920
CAPACITY OF DIMINISHING THE

1454
00:51:45,920 --> 00:51:47,440
INTERACTION OF THE VIRUS TO

1455
00:51:47,440 --> 00:51:49,920
INTERACT WITH CELLS INDEPENDENT

1456
00:51:49,920 --> 00:51:51,440
OF PHASE 2, WE BELIEVE THAT IS

1457
00:51:51,440 --> 00:51:53,600
AN IMPORTANT ELEMENT OF THIS

1458
00:51:53,600 --> 00:51:54,200
MECHANISM.

1459
00:51:54,200 --> 00:51:55,680
WE ALSO DON'T HAVE MUCH MORE

1460
00:51:55,680 --> 00:51:56,640
UNDERSTANDING OF THE NUMBER OF

1461
00:51:56,640 --> 00:51:57,960
OTHER ANTIBODIES THAT BRINING

1462
00:51:57,960 --> 00:52:02,240
THE RBD OUTSIDE OF THE RECEPTOR

1463
00:52:02,240 --> 00:52:03,840
BINDING MOTIF AND THEIR MEEK

1464
00:52:03,840 --> 00:52:04,720
ANYMORES SO LET ME TURN YOUR

1465
00:52:04,720 --> 00:52:06,880
ATTENTION TO ANOTHER PANEL

1466
00:52:06,880 --> 00:52:08,240
MONOCLONALS WE HAVE BEEN

1467
00:52:08,240 --> 00:52:09,640
CHARACTERIZING COLLABORATION

1468
00:52:09,640 --> 00:52:10,320
WITH MICHAEL DIAMONDs

1469
00:52:10,320 --> 00:52:11,800
LABORATORY AT WASU.

1470
00:52:11,800 --> 00:52:16,440
SO WE MADE A LARGE PANEL RBD

1471
00:52:16,440 --> 00:52:17,760
SPECIFIC MONOCLONAL, I WILL TELL

1472
00:52:17,760 --> 00:52:20,240
YOU ABOUT ONE OF THEM IN

1473
00:52:20,240 --> 00:52:28,440
PARTICULAR, AND THAT IS THE

1474
00:52:28,440 --> 00:52:29,960
ANTIBODY SARS 238 ACTIVE IN

1475
00:52:29,960 --> 00:52:32,360
VITRO AS WELL AS IN VIVO AND

1476
00:52:32,360 --> 00:52:34,040
PROPHYLACTIC STUDY AS WELL AS

1477
00:52:34,040 --> 00:52:35,040
THERAPEUTICALLY AND ALSO

1478
00:52:35,040 --> 00:52:40,240
EXHIBITS QUITE HIGH SPECIFIC

1479
00:52:40,240 --> 00:52:40,480
ACTIVITY.

1480
00:52:40,480 --> 00:52:42,520
SO MY GRADUATE STUDENT WAS ABLE

1481
00:52:42,520 --> 00:52:43,960
TO DETERMINE THE STRUCTURE OF

1482
00:52:43,960 --> 00:52:45,920
THIS MONOCLONAL AND WE FIND THAT

1483
00:52:45,920 --> 00:52:48,040
IT BINDS KIND OF A UNIQUE

1484
00:52:48,040 --> 00:52:51,080
EPITOPE AT THE EDGE AND IT DOES

1485
00:52:51,080 --> 00:52:53,200
OVERLAP WITH PHASE 2 BINDING

1486
00:52:53,200 --> 00:52:55,400
SITE BUT WE FOUND QUITE

1487
00:52:55,400 --> 00:52:57,520
INTERESTING IS AN ANTIBODY

1488
00:52:57,520 --> 00:52:59,840
ENTIRELY DRIVEN FROM LIGHT CHAIN

1489
00:52:59,840 --> 00:53:01,680
CONTEXT, 70% INTERFACE IS LIGHT

1490
00:53:01,680 --> 00:53:04,280
CHAIN CDR LOOPS WHICH IS UNUSUAL

1491
00:53:04,280 --> 00:53:05,640
SITUATION WHERE MOST MONOCLONALS

1492
00:53:05,640 --> 00:53:07,720
GO THE OTHER WAY.

1493
00:53:07,720 --> 00:53:12,200
7 TO 080% SPECIFIC CONTEXT BY

1494
00:53:12,200 --> 00:53:13,040
HEAVY CHAIN CONTEXT.

1495
00:53:13,040 --> 00:53:15,240
WE ALSO NOTICE THE EPITOPE

1496
00:53:15,240 --> 00:53:17,240
ITSELF IS -- HIGHLY CONSERVED

1497
00:53:17,240 --> 00:53:17,960
AMONG THE VARIANTS THAT ARE

1498
00:53:17,960 --> 00:53:19,680
CIRCULATING.

1499
00:53:19,680 --> 00:53:22,800
IN FACT, THE OVERLYING MAJORITY

1500
00:53:22,800 --> 00:53:24,000
OF THE GRANTS CONCERN THAT WE

1501
00:53:24,000 --> 00:53:26,080
TESTED FOR NEUTRALIZATION BY

1502
00:53:26,080 --> 00:53:28,920
SARS 38 IN FACT WERE POTENTLY

1503
00:53:28,920 --> 00:53:29,480
NEUTRALIZED.

1504
00:53:29,480 --> 00:53:31,880
EXCEPT I WILL TELL YOU THE PUNCH

1505
00:53:31,880 --> 00:53:33,640
LINE EXCEPT FOR OMICRON.

1506
00:53:33,640 --> 00:53:35,040
OMICRON IS NOT NEUTRALIZED WELL

1507
00:53:35,040 --> 00:53:39,040
BY THIS MONOCLONAL.

1508
00:53:39,040 --> 00:53:40,560
SO WE ALSO CARRIED OUT A NUMBER

1509
00:53:40,560 --> 00:53:42,200
OF STUDIES LOOKING AT ANTIBODIES

1510
00:53:42,200 --> 00:53:45,720
AGAINST THE MTD, THE EXTERNAL

1511
00:53:45,720 --> 00:53:47,760
DOMAIN OF THE SPIKE.

1512
00:53:47,760 --> 00:53:51,280
SO THE MECHANISM OF ACTION THESE

1513
00:53:51,280 --> 00:53:53,720
NTD ANTIBODIES IS ENIGMATIC.

1514
00:53:53,720 --> 00:53:55,960
WE GROUPED THEM INTO THREE

1515
00:53:55,960 --> 00:53:57,440
COMPETITION GROUPS AND PROCEEDED

1516
00:53:57,440 --> 00:54:02,280
TO DO A NUMBER OF ASSAYS

1517
00:54:02,280 --> 00:54:04,360
EVALUATING DISRUPTING ACE 2

1518
00:54:04,360 --> 00:54:05,840
BINDING CAPABLE OF DOING AND

1519
00:54:05,840 --> 00:54:08,760
CROSS COMPETING WITH OTHER KNOWN

1520
00:54:08,760 --> 00:54:11,360
ANTIBODIES TO DETERMINE EPITOPES

1521
00:54:11,360 --> 00:54:13,960
BUT ONE STRIKING THING, WE HAVE

1522
00:54:13,960 --> 00:54:15,520
THREE COMPETITION GROUPS ONLY

1523
00:54:15,520 --> 00:54:19,720
GROUP ONE SHOWN HERE ACTUALLY

1524
00:54:19,720 --> 00:54:22,360
POTENTLY STAND COVID INFECTED

1525
00:54:22,360 --> 00:54:23,960
CELLS.

1526
00:54:23,960 --> 00:54:25,240
IN FACT IT STAINS THE CELLS

1527
00:54:25,240 --> 00:54:27,880
BETTER THAN THE RBD ANTIBODIES

1528
00:54:27,880 --> 00:54:29,280
WHICH USE HERE AS CONTROLS SO

1529
00:54:29,280 --> 00:54:33,040
THE RBD ANTIBODIES CAN FAIRLY

1530
00:54:33,040 --> 00:54:34,960
WELL STAIN, IT IS QUITE WELL

1531
00:54:34,960 --> 00:54:37,640
APPRECIATIVE THAT THE EFFECTOR

1532
00:54:37,640 --> 00:54:39,400
FUNCTION IS MECHANISM RBD

1533
00:54:39,400 --> 00:54:40,840
ANTIBODIES CAN WORK, IT WAS

1534
00:54:40,840 --> 00:54:42,360
RATHER DRAMATIC HOW THE GROUP

1535
00:54:42,360 --> 00:54:46,800
ONE BUT NOT GROUP 2 AND 3 M

1536
00:54:46,800 --> 00:54:47,800
TEXAS ANTIBODIES STAIN INFECTED

1537
00:54:47,800 --> 00:54:49,600
CELLS, HYPOTHESIS DERIVE THIS IS

1538
00:54:49,600 --> 00:54:52,280
THE MECHANISMS OF THE IN VIVO

1539
00:54:52,280 --> 00:54:53,800
PROTECTION MIGHT BE DRIVEN BY FC

1540
00:54:53,800 --> 00:54:55,760
MEDIATED PROCESSES.

1541
00:54:55,760 --> 00:55:00,360
WHEN WE MUTATE CRITICAL GLYCAN

1542
00:55:00,360 --> 00:55:02,160
RESIDUE MANY THE FC REGION WE

1543
00:55:02,160 --> 00:55:03,840
LOSE A SIGNIFICANT ASPECT OF THE

1544
00:55:03,840 --> 00:55:06,040
POTENCY OF PROTECTION.

1545
00:55:06,040 --> 00:55:09,520
WITH THIS PARTICULAR ANTIBODY

1546
00:55:09,520 --> 00:55:13,600
SARS 257.

1547
00:55:13,600 --> 00:55:15,880
SO LUCAS ADAMS IN MY GROUP WENT

1548
00:55:15,880 --> 00:55:18,040
TO DETERMINE THE THE CRYOEM

1549
00:55:18,040 --> 00:55:20,000
STRUCTURE OF THE MONOCLONAL

1550
00:55:20,000 --> 00:55:22,640
ANTIBODY BOUND TO END TERMINAL

1551
00:55:22,640 --> 00:55:24,440
DOMAIN OF TRIAL RICK SPIKE AND

1552
00:55:24,440 --> 00:55:28,920
IT BINDS TO HE WILL -- TRIAL

1553
00:55:28,920 --> 00:55:29,600
TRIMERIC SPIKE.

1554
00:55:29,600 --> 00:55:33,600
AND BINDS TO OTHER ANTIBODIES

1555
00:55:33,600 --> 00:55:36,480
COMBINE PROPOSED OF PREAN AREA

1556
00:55:36,480 --> 00:55:40,080
THAT HAS BEEN TERMED THE NTD

1557
00:55:40,080 --> 00:55:41,000
SUPERSITE.

1558
00:55:41,000 --> 00:55:43,040
SO IF YOU EVALUATE THE ACTUAL

1559
00:55:43,040 --> 00:55:44,440
EPITOPE AND LOOK AT WHERE THE

1560
00:55:44,440 --> 00:55:46,280
VARIANTS OF CONCERN AS WELL AS

1561
00:55:46,280 --> 00:55:48,800
ESCAPE MUTANTS WE DEVELOPED IN

1562
00:55:48,800 --> 00:55:51,080
COLLABORATION WITH SEAN WHELIN'S

1563
00:55:51,080 --> 00:55:53,040
GROUP WE CAN APPRECIATE THAT IN

1564
00:55:53,040 --> 00:55:54,600
FACT WHAT WAS A FAIR DEGREE OF

1565
00:55:54,600 --> 00:55:56,600
CONSERVATION WE DO HAVE A COUPLE

1566
00:55:56,600 --> 00:56:01,240
DELETIONS IN THE CASE OF THE 351

1567
00:56:01,240 --> 00:56:04,280
AND 630 GRANTS OF CONCERN WHICH

1568
00:56:04,280 --> 00:56:06,240
INTRODUCE DELETIONS AT THE CRUX

1569
00:56:06,240 --> 00:56:10,920
OF THE EPITOPE SO WE GO LOSE

1570
00:56:10,920 --> 00:56:14,360
PROTECTIVE VALUE OR

1571
00:56:14,360 --> 00:56:15,560
NEUTRALIZATION WITH ANTIBODY

1572
00:56:15,560 --> 00:56:17,800
UNDER THESE CIRCULATING STRAINS.

1573
00:56:17,800 --> 00:56:19,480
WE HAVE A REGION IN OMICRON TO

1574
00:56:19,480 --> 00:56:21,440
CUT TO THE QUICK, DATA NOT SHOWN

1575
00:56:21,440 --> 00:56:23,400
WE ALSO LOSE ANY NEUTRALIZATION

1576
00:56:23,400 --> 00:56:25,080
PROTECTION AGAINST OMICRON WITH

1577
00:56:25,080 --> 00:56:26,640
THIS ANTIBODY.

1578
00:56:26,640 --> 00:56:27,880
SO WHAT ABOUT OMICRON, WHAT WE

1579
00:56:27,880 --> 00:56:28,320
REALLY KNOW?

1580
00:56:28,320 --> 00:56:30,760
OF COURSE WE KNOW RELATIVE TO

1581
00:56:30,760 --> 00:56:32,160
ALL PROCEEDINGS VARIANTS OF

1582
00:56:32,160 --> 00:56:34,240
CONCERN WILL IS A SIGNIFICANTLY

1583
00:56:34,240 --> 00:56:36,760
INCREASED NUMBER OF AMINO ACID

1584
00:56:36,760 --> 00:56:37,680
SUBSTITUTIONS THROUGHOUT THE RBD

1585
00:56:37,680 --> 00:56:40,040
AS WELL AS THE NTD.

1586
00:56:40,040 --> 00:56:42,440
WE NOTE THAT MANY OF THOSE

1587
00:56:42,440 --> 00:56:44,240
MUTATIONS WHICH HAVE BEEN

1588
00:56:44,240 --> 00:56:45,720
IDENTIFIED ALL ACTUALLY IN THE

1589
00:56:45,720 --> 00:56:48,200
RECEPTOR BINDING MOTIF AND MANY

1590
00:56:48,200 --> 00:56:50,240
OF THEM IN CRITICAL LOCATIONS

1591
00:56:50,240 --> 00:56:54,080
THAT ARE QUOTE DISRUPTIVE

1592
00:56:54,080 --> 00:56:55,840
TOWARDS IMMUNE ANTIBODIES SO WE

1593
00:56:55,840 --> 00:56:57,840
WANTED TO FURTHER EVALUATE THAT

1594
00:56:57,840 --> 00:56:59,160
IN COLLABORATION WITH MICHAEL

1595
00:56:59,160 --> 00:57:00,800
DIAMOND'S LABORATORY.

1596
00:57:00,800 --> 00:57:04,360
WE TOOK ALL OF THE EMERGENCY USE

1597
00:57:04,360 --> 00:57:06,240
AUTHORIZED ANTIBODIES AS WELL AS

1598
00:57:06,240 --> 00:57:08,680
OUR OWN MORE POTENTLY SPECIFIC

1599
00:57:08,680 --> 00:57:11,920
ANTIBODIES AND EVALUATED

1600
00:57:11,920 --> 00:57:13,040
CAPACITY TO BE NEUTRALIZED.

1601
00:57:13,040 --> 00:57:18,160
THIS IS A COMPLETELY IN VITRO

1602
00:57:18,160 --> 00:57:20,920
ASSAY USING AUTHENTIC VIRUS AND

1603
00:57:20,920 --> 00:57:22,880
WHAT WE FOUND JUST PUBLISHED A

1604
00:57:22,880 --> 00:57:26,360
WEEK OR TWO AGO IS THAT OF THE

1605
00:57:26,360 --> 00:57:28,240
EMERGENCY USE AUTHORIZED

1606
00:57:28,240 --> 00:57:32,880
ANTIBODIES ONLY THE VRGSK S 3L 9

1607
00:57:32,880 --> 00:57:33,840
HAS ANY CAPACITY OF

1608
00:57:33,840 --> 00:57:34,440
NEUTRALIZING.

1609
00:57:34,440 --> 00:57:36,240
IT IS NOT A VERY POTENT

1610
00:57:36,240 --> 00:57:37,280
NEUTRALIZING ANN BODY IN

1611
00:57:37,280 --> 00:57:38,920
GENERAL, BUT IT DOESN'T LOSE

1612
00:57:38,920 --> 00:57:40,760
MUCH POTENCY AGAINST OMICRON.

1613
00:57:40,760 --> 00:57:44,240
AND THEN WE ALSO FOUND THAT THE

1614
00:57:44,240 --> 00:57:45,840
ASTRA ZENECA PROPHYLACTIC

1615
00:57:45,840 --> 00:57:47,560
ANTIBODIES DEVELOPED BY JIM CROW

1616
00:57:47,560 --> 00:57:50,040
AT VANDERBILT ALSO MAINTAIN

1617
00:57:50,040 --> 00:57:52,560
COLLECTIVELY TOGETHER FAIRLY

1618
00:57:52,560 --> 00:57:53,680
REASONABLE NEUTRALIZATION

1619
00:57:53,680 --> 00:57:56,720
CAPACITY AGAINST OMICRON.

1620
00:57:56,720 --> 00:57:58,640
AND THAT IS WHAT WE LEARNED SO

1621
00:57:58,640 --> 00:57:59,400
FAR.

1622
00:57:59,400 --> 00:58:00,320
AND THE EXPECTATIONS WITH OF

1623
00:58:00,320 --> 00:58:02,520
COURSE THE DEVELOPMENT OF NEXT

1624
00:58:02,520 --> 00:58:04,600
GENERATION MONOCLONALS IS

1625
00:58:04,600 --> 00:58:06,080
HOPEFULLY FIND SOME MONOCLONALS

1626
00:58:06,080 --> 00:58:07,520
THAT HAVE BETTER TIME DEALING

1627
00:58:07,520 --> 00:58:09,600
WITH BROAD SPECTRUM OF DIFFERENT

1628
00:58:09,600 --> 00:58:10,440
VARIANTS OF CONCERN.

1629
00:58:10,440 --> 00:58:12,200
SO I WANT TO THANK MY

1630
00:58:12,200 --> 00:58:13,640
COLLABORATORS AND MY STUDENTS

1631
00:58:13,640 --> 00:58:15,320
AND POST DOCS WORKING ON THESE

1632
00:58:15,320 --> 00:58:16,160
PROJECTS AND THANK YOU FOR YOUR

1633
00:58:16,160 --> 00:58:19,000
ATTENTION.

1634
00:58:19,000 --> 00:58:21,320
>> THANK YOU SO MUCH.

1635
00:58:21,320 --> 00:58:22,800
AGAIN, PLEASE RAISE YOUR HAND IF

1636
00:58:22,800 --> 00:58:29,360
YOU HAVE A QUESTION.

1637
00:58:29,360 --> 00:58:31,440
>> I WAS WONDERING SO VIKING

1638
00:58:31,440 --> 00:58:33,640
NONE OF THESE ANTIBODIES BIND TO

1639
00:58:33,640 --> 00:58:34,400
S PROTEIN.

1640
00:58:34,400 --> 00:58:36,040
AND I WAS WONDERING HOW IS THE

1641
00:58:36,040 --> 00:58:39,960
STRUCTURE OF MERS DIFFERENT FROM

1642
00:58:39,960 --> 00:58:40,440
SARS COV-2?

1643
00:58:40,440 --> 00:58:42,360
DOES THAT SAY SOMETHING ABOUT

1644
00:58:42,360 --> 00:58:45,160
HOW THESE ANTIBODIES ARE GOING

1645
00:58:45,160 --> 00:58:45,640
TO BIND?

1646
00:58:45,640 --> 00:58:46,240
IS THERE A CHANGE IN THE

1647
00:58:46,240 --> 00:58:48,040
STRUCTURE THAT'S GOING TO

1648
00:58:48,040 --> 00:58:48,880
PREVENT ANY ANTIBODIES FROM

1649
00:58:48,880 --> 00:58:52,720
BINDING?

1650
00:58:52,720 --> 00:58:54,640
THE RECEPTOR BINDING REGION OF

1651
00:58:54,640 --> 00:58:57,440
MERS IS DRAMATICALLY ALTERED

1652
00:58:57,440 --> 00:58:59,000
RELATIVE TO SARS 1 AND 2.

1653
00:58:59,000 --> 00:59:00,960
THERE ARE ANTIBODIES IDENTIFIED

1654
00:59:00,960 --> 00:59:03,320
WHICH ARE CROSS REACTIVE BETWEEN

1655
00:59:03,320 --> 00:59:05,080
MERS AND SARS BUT SAFE TO SAY

1656
00:59:05,080 --> 00:59:06,720
THEY ARE NOT NEUTRALIZING

1657
00:59:06,720 --> 00:59:09,560
PROTECTIVE OR AT LEAST NOT

1658
00:59:09,560 --> 00:59:11,240
NEUTRALIZED.

1659
00:59:11,240 --> 00:59:13,960
SO WE HAVE IDENTIFIED FROM SOME

1660
00:59:13,960 --> 00:59:15,520
MOUSE PANELS SOME CROSS

1661
00:59:15,520 --> 00:59:18,040
REACTIVITY TO MERS BUT THEY ARE

1662
00:59:18,040 --> 00:59:22,240
NOT NEUTRALIZING ANTIBODIES.

1663
00:59:22,240 --> 00:59:23,840
CERTAINLY I THINK THAT ONE WILL

1664
00:59:23,840 --> 00:59:25,760
FIND THAT MOST ANTIBODIES WHICH

1665
00:59:25,760 --> 00:59:27,400
ARE CROSS REACTIVE IN THIS WAY

1666
00:59:27,400 --> 00:59:29,560
ARE AGAINST S 2 SO THEY ARE

1667
00:59:29,560 --> 00:59:32,440
GOING TO BE IGNORING THE RBD AND

1668
00:59:32,440 --> 00:59:33,960
NTD REGIONS WHICH IS WHAT I HAVE

1669
00:59:33,960 --> 00:59:37,880
BEEN TALKING ABOUT TODAY.

1670
00:59:37,880 --> 00:59:38,840
>> THANK YOU.

1671
00:59:38,840 --> 00:59:47,600
ANY OTHER QUESTIONS?

1672
00:59:47,600 --> 00:59:51,640
AGAIN WE'LL HAVE TIME AT THE

1673
00:59:51,640 --> 00:59:51,800
END.

1674
00:59:51,800 --> 00:59:55,560
THANKS SO MUCH, THE NEXT SPEAKER

1675
00:59:55,560 --> 00:59:56,560
IS RAFI AHMED.

1676
00:59:56,560 --> 00:59:58,120
WHO WILL BE TALKING ABOUT

1677
00:59:58,120 --> 00:59:59,880
LONGITUDINAL ANALYSIS OF

1678
00:59:59,880 --> 01:00:01,640
ADAPTIVE IMMUNITY FOLLOWING MILD

1679
01:00:01,640 --> 01:00:25,000
TO MODERATE COVID-19.

1680
01:00:25,000 --> 01:00:26,200
>> CAN YOU SEE MY SLIDES?

1681
01:00:26,200 --> 01:00:27,920
>> YES, REFA.

1682
01:00:27,920 --> 01:00:28,280
>> GREAT.

1683
01:00:28,280 --> 01:00:32,440
I'LL PRESENT TO YOU SOME OF THE

1684
01:00:32,440 --> 01:00:38,000
-- THIS IS A COLLABORATIVE STUDY

1685
01:00:38,000 --> 01:00:45,680
WITH -- COLLABORATIVE STUDY WITH

1686
01:00:45,680 --> 01:00:48,440
JUDY AT HUTCH.

1687
01:00:48,440 --> 01:00:51,880
AND WE HAVE BEEN FOLLOWING

1688
01:00:51,880 --> 01:00:53,880
LONGITUDINALLY RESPONSES IN

1689
01:00:53,880 --> 01:00:54,880
COVID-19 PATIENT.

1690
01:00:54,880 --> 01:00:56,840
THIS IS ACTUALLY A VERY NICE

1691
01:00:56,840 --> 01:00:58,520
COHORT.

1692
01:00:58,520 --> 01:01:04,480
WE NOW HAVE SLIGHT -- OVER 450

1693
01:01:04,480 --> 01:01:05,840
CONVALESCENT PATIENTS WE

1694
01:01:05,840 --> 01:01:08,280
FOLLOWED BUT PARTICULARLY THE

1695
01:01:08,280 --> 01:01:12,840
COHORT AT THE ATLANTA AND SEE

1696
01:01:12,840 --> 01:01:13,520
SEATTLE.

1697
01:01:13,520 --> 01:01:18,600
AND OVER 90% CONVALESCENT

1698
01:01:18,600 --> 01:01:19,080
PATIENTS (INAUDIBLE).

1699
01:01:19,080 --> 01:01:22,080
WHICH IS NICE BECAUSE IT

1700
01:01:22,080 --> 01:01:25,160
REFLECTS THE INFECTION MAJORITY

1701
01:01:25,160 --> 01:01:25,760
OF (INAUDIBLE).

1702
01:01:25,760 --> 01:01:28,920
WHAT I'M GOING TO DO IN MY TALK

1703
01:01:28,920 --> 01:01:33,680
TODAY IS DESCRIBE THE ANTIBODY

1704
01:01:33,680 --> 01:01:36,480
RESPONSE AND THEN JUDY WILL

1705
01:01:36,480 --> 01:01:37,600
FOLLOW, SHE WILL GIVE MORE

1706
01:01:37,600 --> 01:01:39,360
INFORMATION OBJECT COHORT

1707
01:01:39,360 --> 01:01:39,800
ITSELF.

1708
01:01:39,800 --> 01:01:43,880
AND THEN TALK ABOUT THE CELLULAR

1709
01:01:43,880 --> 01:01:45,120
(INAUDIBLE).

1710
01:01:45,120 --> 01:01:47,920
SO I'LL ADDRESS TWO QUESTIONS IN

1711
01:01:47,920 --> 01:01:49,040
MY TALK TODAY.

1712
01:01:49,040 --> 01:01:52,920
FIRST ONE IS HOW DOES ANTIBODY

1713
01:01:52,920 --> 01:01:57,320
TITERS CHANGE OVER THIS 18 MONTH

1714
01:01:57,320 --> 01:01:58,640
PERIOD WITH INFECTED INDIVIDUALS

1715
01:01:58,640 --> 01:02:02,320
AND I SHOW YOU DATA LOOKING AT

1716
01:02:02,320 --> 01:02:06,880
BINDING ANTIBODY NEUTRALIZINGS

1717
01:02:06,880 --> 01:02:08,400
ANTIBODIES USING A (INAUDIBLE).

1718
01:02:08,400 --> 01:02:10,840
I WILL ADDRESS THE DIGRESS FROM

1719
01:02:10,840 --> 01:02:18,760
THE MAIN TOPIC DURABILITY AND

1720
01:02:18,760 --> 01:02:20,360
ADDRESS QUESTIONS WHAT HAPPENS

1721
01:02:20,360 --> 01:02:23,680
TO ANTIBODY RESPONSES TO THE

1722
01:02:23,680 --> 01:02:27,000
ENDEMIC CORONA VIRUS, INFECTIONS

1723
01:02:27,000 --> 01:02:27,640
WE CHANNEL.

1724
01:02:27,640 --> 01:02:30,120
THAT'S THE SARS COV-2 INFECTION,

1725
01:02:30,120 --> 01:02:33,000
IN FACT, THOSE TITERS MORE

1726
01:02:33,000 --> 01:02:34,040
IMPORTANTLY THE MESSAGE I WANT

1727
01:02:34,040 --> 01:02:37,480
TO ADDRESS IN THIS TALK IS

1728
01:02:37,480 --> 01:02:42,040
DURABILITY OF ANTIBODY RESPONSES

1729
01:02:42,040 --> 01:02:47,040
TO THE (INAUDIBLE).

1730
01:02:47,040 --> 01:02:48,760
SO THIS A DISEASE SLIDE I WILL

1731
01:02:48,760 --> 01:02:49,200
WALK YOU THROUGH.

1732
01:02:49,200 --> 01:02:55,480
SO THIS IS LOOKING

1733
01:02:55,480 --> 01:02:58,440
LONGITUDINALLY IN OVER 200 OF

1734
01:02:58,440 --> 01:03:00,600
OUR COHORT LOOKING AT ANTIBODY

1735
01:03:00,600 --> 01:03:03,240
RESPONSES TO EITHER THE SPIKE

1736
01:03:03,240 --> 01:03:05,800
PROTEIN, THE RBD REGION OR THE

1737
01:03:05,800 --> 01:03:07,000
NTD REGION.

1738
01:03:07,000 --> 01:03:11,680
AND WE HAVE LOOKED AT IGG IGA

1739
01:03:11,680 --> 01:03:15,680
AND IG -- LET'S FOCUS ON THIS

1740
01:03:15,680 --> 01:03:17,800
PARTICULAR -- WHICH IS SHOWING

1741
01:03:17,800 --> 01:03:20,840
LONGITUDINAL ANTIBODY RESPONSES

1742
01:03:20,840 --> 01:03:23,440
IGG RESPONSES TO THE SARS COV-2

1743
01:03:23,440 --> 01:03:26,320
SPIKE PROTEIN.

1744
01:03:26,320 --> 01:03:28,680
IN RED ARE PRE-PANDEMIC SAMPLES,

1745
01:03:28,680 --> 01:03:30,800
THESE ACTUALLY SERVE NEGATIVE

1746
01:03:30,800 --> 01:03:33,480
CONTROL, THESE ARE SOME SAMPLES

1747
01:03:33,480 --> 01:03:37,600
FROM STUDIES WE HAD DONE IN 2018

1748
01:03:37,600 --> 01:03:40,040
AND EARLIER LOOKING AT EITHER

1749
01:03:40,040 --> 01:03:43,640
LONGITUDINAL ANALYSIS OF PEOPLE

1750
01:03:43,640 --> 01:03:46,040
WHO GOT DISEASE AND FLU VACCINE

1751
01:03:46,040 --> 01:03:50,520
OR THERAPY -- THESE ARE DATA

1752
01:03:50,520 --> 01:03:53,360
FROM 2010, ANOTHER ONE AT 2014.

1753
01:03:53,360 --> 01:03:57,360
AND THIS SHOWS YOU THAT LOOKING

1754
01:03:57,360 --> 01:03:59,560
LONGITUDINALLY THESE INDIVIDUALS

1755
01:03:59,560 --> 01:04:03,040
FROM THE PANDEMIC NOT GETTING

1756
01:04:03,040 --> 01:04:04,640
INFECTION VACCINE IS PRETTY

1757
01:04:04,640 --> 01:04:05,040
FLAT.

1758
01:04:05,040 --> 01:04:07,640
SO THAT IS A NICE NEGATIVE OF

1759
01:04:07,640 --> 01:04:08,040
THIS.

1760
01:04:08,040 --> 01:04:10,240
SO WHAT THIS SHOWS ALMOST ALL OF

1761
01:04:10,240 --> 01:04:13,400
THESE PATIENTS MADE A NICE IGG

1762
01:04:13,400 --> 01:04:14,720
RESPONSE, CAME UP VERY QUICKLY

1763
01:04:14,720 --> 01:04:17,280
AND THEN YOU CALCULATE THE

1764
01:04:17,280 --> 01:04:22,840
DURABILITY OF THE RESPONSE WE

1765
01:04:22,840 --> 01:04:25,600
USE A (INAUDIBLE) GROUP AND IT

1766
01:04:25,600 --> 01:04:27,920
MADE -- GOT TO AN INTERESTING

1767
01:04:27,920 --> 01:04:31,360
POINT, THAT IF YOU DO JUST

1768
01:04:31,360 --> 01:04:34,640
EXPONENTIAL OVER THIS PERIOD YOU

1769
01:04:34,640 --> 01:04:37,040
GET HALF LIFE BUT IF YOU DO USE

1770
01:04:37,040 --> 01:04:39,160
THIS PARALLEL METHOD WHICH

1771
01:04:39,160 --> 01:04:40,920
ALLOWS YOU U TO LOOK AT BIPHASIC

1772
01:04:40,920 --> 01:04:42,920
ASPECTS OF THE RESPONSE YOU SEE

1773
01:04:42,920 --> 01:04:44,160
SOMETHING VERY INTERESTING, YOU

1774
01:04:44,160 --> 01:04:46,320
SEE THAT THERE IS A SLIGHTLY

1775
01:04:46,320 --> 01:04:49,840
FASTER INITIAL DECLINE BUT THEN

1776
01:04:49,840 --> 01:04:53,640
IF YOU DO -- FROM AROUND LIKE

1777
01:04:53,640 --> 01:04:56,520
THIS TIME POINT IN LIKE 100 DAY,

1778
01:04:56,520 --> 01:04:58,480
IT JUST STARTS TO BECOME -- YOU

1779
01:04:58,480 --> 01:05:01,160
CAN SEE THIS GREEN CURVE IS NOW

1780
01:05:01,160 --> 01:05:03,640
MOVED UP AND WHEN YOU LOOK AT

1781
01:05:03,640 --> 01:05:05,840
WHICH CURVE PREDICTS RESPONSE,

1782
01:05:05,840 --> 01:05:07,640
SO ESSENTIALLY WHAT YOU ARE

1783
01:05:07,640 --> 01:05:11,800
LOOKING AT IS INITIAL BURST UP

1784
01:05:11,800 --> 01:05:17,760
DECLINING AND THEN SLIGHTLY FAST

1785
01:05:17,760 --> 01:05:20,240
AERATED AND THERE THE FIRST BUT

1786
01:05:20,240 --> 01:05:24,760
THEN GIVING YOU A SLOWER -- THIS

1787
01:05:24,760 --> 01:05:26,880
IS CONSISTENT HOW WE LOOK AT

1788
01:05:26,880 --> 01:05:30,440
ANTIBODY FUNCTION, THIS ISSUE

1789
01:05:30,440 --> 01:05:32,440
THIS INTERESTING ISSUE OF EXTRA

1790
01:05:32,440 --> 01:05:33,920
FOLLICULAR ANTIBODY RESPONSES TO

1791
01:05:33,920 --> 01:05:35,040
STUDIES THAT YOU HAVE THEN

1792
01:05:35,040 --> 01:05:38,360
EITHER IN MOUSE MODELS OF

1793
01:05:38,360 --> 01:05:42,600
INFECTION AND ALSO IN HUMAN

1794
01:05:42,600 --> 01:05:42,840
STUDIES.

1795
01:05:42,840 --> 01:05:48,320
HUMANS AFTER VACCINATION VACCINE

1796
01:05:48,320 --> 01:05:49,800
OR (INAUDIBLE) VACCINE RESPONSE,

1797
01:05:49,800 --> 01:05:51,520
ANTIBODY COMES UP VERY QUICK

1798
01:05:51,520 --> 01:05:53,440
WITHIN TWO TO THREE WEEKS YOU

1799
01:05:53,440 --> 01:05:55,440
WILL HAVE ACTUALLY

1800
01:05:55,440 --> 01:05:56,880
ENVIRONMENTALLY BECOMING UP

1801
01:05:56,880 --> 01:05:58,440
VACCINATION BUT INFECTION WITH

1802
01:05:58,440 --> 01:06:00,440
NAIVE INDIVIDUAL, AND MOST OF

1803
01:06:00,440 --> 01:06:04,520
THIS ALREADY HAS SWITCHED, YOU

1804
01:06:04,520 --> 01:06:06,240
HAVE A LOT ALREADY SWITCHED.

1805
01:06:06,240 --> 01:06:11,240
MOST IS EXTRA FOLLICULAR BUT SO

1806
01:06:11,240 --> 01:06:13,320
THIS IS EVEN PRE-GERM CENTER

1807
01:06:13,320 --> 01:06:18,040
FORMATION THAT YOU GET THIS

1808
01:06:18,040 --> 01:06:19,880
BURST OF ICE TYPE ANTIBODIES

1809
01:06:19,880 --> 01:06:22,040
WITHIN A COUPLE OF WEEKS AND

1810
01:06:22,040 --> 01:06:23,280
AGAIN FROM ANIMAL STUDIES WE

1811
01:06:23,280 --> 01:06:25,400
KNOW MOST OF THAT IS EXTRA

1812
01:06:25,400 --> 01:06:27,320
FOLLICULAR HAPPENING OUTSIDE, IT

1813
01:06:27,320 --> 01:06:29,640
IS EXTRA FOLLICULAR AN THESE

1814
01:06:29,640 --> 01:06:32,360
WOULD BE VERY LOW (INAUDIBLE)

1815
01:06:32,360 --> 01:06:32,800
MUTATION.

1816
01:06:32,800 --> 01:06:35,040
VERY LIKELY THE MAJORITY OF

1817
01:06:35,040 --> 01:06:36,280
INCIDENCE WILL BE SHORTER THAN

1818
01:06:36,280 --> 01:06:38,320
PLASMA BLASTS OR BLAST CELLS AND

1819
01:06:38,320 --> 01:06:39,720
EVEN BONE MARROW (INAUDIBLE)

1820
01:06:39,720 --> 01:06:41,640
THIS IS IN SOME WAY THE TIP OF

1821
01:06:41,640 --> 01:06:44,960
THIS AS THE EFFECTOR RESPONSE

1822
01:06:44,960 --> 01:06:49,920
COMING UP RAPIDSLY BUT THEN AS

1823
01:06:49,920 --> 01:06:52,600
(INAUDIBLE) START FORMING IN A

1824
01:06:52,600 --> 01:06:56,440
FEW WEEKS AND SHANE AND ALI

1825
01:06:56,440 --> 01:06:57,400
SHOWN EGG GANTLY YOU CAN THEN IS

1826
01:06:57,400 --> 01:07:00,440
WHEN YOU START GETTING THE

1827
01:07:00,440 --> 01:07:04,400
SOMATIC HYPERMUTATION BONE

1828
01:07:04,400 --> 01:07:06,440
MARROW, I THINK THIS IS

1829
01:07:06,440 --> 01:07:08,000
REFLECTIVE OF THE RESPONSE THAT

1830
01:07:08,000 --> 01:07:10,000
ONE HAS TYPICALLY SEEN IN ANIMAL

1831
01:07:10,000 --> 01:07:13,040
MODELS.

1832
01:07:13,040 --> 01:07:16,000
SO THIS WAS VERY NICE GETTING

1833
01:07:16,000 --> 01:07:19,040
THIS NICE BIPHASIC, THE NEXT

1834
01:07:19,040 --> 01:07:20,960
QUESTION IS UTILIZATION.

1835
01:07:20,960 --> 01:07:23,600
YOU GET A SIMILAR CURVE, SHOWING

1836
01:07:23,600 --> 01:07:25,560
THE BIPHASIC DECAY.

1837
01:07:25,560 --> 01:07:27,400
THIS SHOW IT IS CORRELATION

1838
01:07:27,400 --> 01:07:29,680
BETWEEN BINDING ANTIBODIES AND

1839
01:07:29,680 --> 01:07:31,000
NEUTRALIZING ANTIBODIES, VERY

1840
01:07:31,000 --> 01:07:32,240
NICE CORRELATION.

1841
01:07:32,240 --> 01:07:36,120
ONE THING TO NOTE HERE, IS THAT

1842
01:07:36,120 --> 01:07:39,080
THE NEUTRALIZATION ASSAY OR VERY

1843
01:07:39,080 --> 01:07:42,840
IMPORTANT BIOLOGICALICALLY FORMS

1844
01:07:42,840 --> 01:07:44,200
OFF THE CLIFF GET TO LOWER TITER

1845
01:07:44,200 --> 01:07:46,280
SO WHAT YOU WILL SEE IS THAT

1846
01:07:46,280 --> 01:07:50,440
THERE ARE A LOT OF NEGATIVE FOR

1847
01:07:50,440 --> 01:07:52,640
THE NEUTRALIZATION ASSAY BUT YOU

1848
01:07:52,640 --> 01:07:55,640
STILL ARE GETTING LOWER LEVEL OF

1849
01:07:55,640 --> 01:07:59,640
-- YOU SEE THAT.

1850
01:07:59,640 --> 01:08:01,200
SO FANTASTIC ASSAY BUT

1851
01:08:01,200 --> 01:08:04,320
SENSITIVITY OF THAT IS NOT THE

1852
01:08:04,320 --> 01:08:06,320
GREATEST.  DO TEND THE GET

1853
01:08:06,320 --> 01:08:07,920
THINGS FALLING OFF THE CLIFF

1854
01:08:07,920 --> 01:08:08,320
MORE.

1855
01:08:08,320 --> 01:08:10,280
TO GET IMPRESSION THAT IT HAD

1856
01:08:10,280 --> 01:08:15,640
DROPPED MUCH MORE BUT IN REALITY

1857
01:08:15,640 --> 01:08:16,400
(INAUDIBLE) OKAY.

1858
01:08:16,400 --> 01:08:19,360
THE NEXT QUESTION IS NOW THAT I

1859
01:08:19,360 --> 01:08:23,120
SHORT TN DATA OUT TO ABOUT EIGHT

1860
01:08:23,120 --> 01:08:25,080
MONTHS IN THIS ONE NOW WE HAVE

1861
01:08:25,080 --> 01:08:26,440
THE FOLLOWING SEVERAL OF THESE

1862
01:08:26,440 --> 01:08:31,640
INDIVIDUAL VERSUS NOT BEEN

1863
01:08:31,640 --> 01:08:36,040
VACCINATED, SO NOW GOING OUT

1864
01:08:36,040 --> 01:08:38,360
LEVELS HERE, ARE NOW WE HAVE

1865
01:08:38,360 --> 01:08:41,440
SOME OF THESE INDIVIDUALS THAT

1866
01:08:41,440 --> 01:08:44,240
HAVE NOT BEEN VACCINATED, THEIR

1867
01:08:44,240 --> 01:08:50,040
INFECTION WITH ANTI-DO 
ANTIBODIES, VERY

1868
01:08:50,040 --> 01:08:51,200
STABILIZING EVEN NICE.

1869
01:08:51,200 --> 01:08:55,480
AND NOW THE HALF LIFE OF VALUE

1870
01:08:55,480 --> 01:08:58,360
IS ACTUALLY LIKE A 120 NOW WHICH

1871
01:08:58,360 --> 01:09:02,120
WAS ABOUT 200 DAYS IS EVEN

1872
01:09:02,120 --> 01:09:03,400
STRONGER STATISTICALLY BUT IF

1873
01:09:03,400 --> 01:09:05,320
YOU NOW LOOK AT STARTING AT THE

1874
01:09:05,320 --> 01:09:07,920
YEAR STARTING TO GET NUMBERS OF

1875
01:09:07,920 --> 01:09:10,000
THOUSAND, TO REALLY VAIR VERY

1876
01:09:10,000 --> 01:09:11,720
NICELY BACK IT UP, VERY

1877
01:09:11,720 --> 01:09:13,880
CONSISTENT WITH THE MOTION AND

1878
01:09:13,880 --> 01:09:18,040
CONCEPT OF GENERATING LONGER

1879
01:09:18,040 --> 01:09:20,840
PLASMA CELLS.

1880
01:09:20,840 --> 01:09:22,640
THIS NEUTRALIZATION DATA VERY

1881
01:09:22,640 --> 01:09:24,240
SIMILAR, SMALLER NUMBER HERE BUT

1882
01:09:24,240 --> 01:09:27,960
YOU CAN SEE MANY OF THEM

1883
01:09:27,960 --> 01:09:30,440
(INAUDIBLE) LET ME QUICK WILL I

1884
01:09:30,440 --> 01:09:31,920
ADDRESS THE SECOND POINT --

1885
01:09:31,920 --> 01:09:32,840
QUICKLY ADDRESS THE SECOND

1886
01:09:32,840 --> 01:09:33,040
POINT.

1887
01:09:33,040 --> 01:09:35,120
WHAT IS THE EFFECT OF SARS COV-2

1888
01:09:35,120 --> 01:09:37,920
INFECTION FOR ANTIBODY TITERS TO

1889
01:09:37,920 --> 01:09:41,440
(INAUDIBLE) JUST TO REMIND

1890
01:09:41,440 --> 01:09:45,400
EVERYONE THERE ARE TWO CORONA

1891
01:09:45,400 --> 01:09:47,880
VIRUSES, THERE ARE TWO ALPHA

1892
01:09:47,880 --> 01:09:50,160
CORONA VIRUSES AND TWO BETA

1893
01:09:50,160 --> 01:09:54,120
CORONA VIRUSES HKU 1 AND OC 43.

1894
01:09:54,120 --> 01:09:56,640
THESE INFECTIONS ARE WIDE DURING

1895
01:09:56,640 --> 01:09:59,480
TITER AND VAST MAJORITY OF

1896
01:09:59,480 --> 01:10:05,320
POPULATION IS TO (INAUDIBLE) WE

1897
01:10:05,320 --> 01:10:07,440
HAVE LOOK AT SEVERAL HUNDRED

1898
01:10:07,440 --> 01:10:08,920
INDIVIDUALS, WE HAVE FOUND NO

1899
01:10:08,920 --> 01:10:09,960
ONE NEGATIVE.

1900
01:10:09,960 --> 01:10:12,720
EVERYONE HAS AT SOME POINT BEEN

1901
01:10:12,720 --> 01:10:15,840
INFECTED WITH SOME COMBINATION

1902
01:10:15,840 --> 01:10:18,080
OF HE IS ENDEMIC.

1903
01:10:18,080 --> 01:10:20,560
SO I SHOW YOU THE DATA FROM OUR

1904
01:10:20,560 --> 01:10:26,480
PRE-PANDEMIC SAMPLE.

1905
01:10:26,480 --> 01:10:28,800
GOING BACK TO 2010, 2015, YOU

1906
01:10:28,800 --> 01:10:30,360
CAN SEE THAT TWO POINTS.

1907
01:10:30,360 --> 01:10:34,440
ONE IS THAT EVERYONE IS SERO

1908
01:10:34,440 --> 01:10:35,480
POSITIVE TO THESE CORONA VIRUSES

1909
01:10:35,480 --> 01:10:38,320
AND THE OTHER STRIKING THING

1910
01:10:38,320 --> 01:10:41,120
HERE IS STRAIGHT LINE, PRETTY

1911
01:10:41,120 --> 01:10:43,680
MUCH STRAIGHT LINE, NO HALF LIFE

1912
01:10:43,680 --> 01:10:45,560
AT THIS TIME POINT SO THIS IS

1913
01:10:45,560 --> 01:10:47,440
REFLECTIVE OF INFECTION THAT

1914
01:10:47,440 --> 01:10:48,480
HAPPENED MANY YEARS POSSIBLE

1915
01:10:48,480 --> 01:10:51,160
SOME BOOSTING SOME REINFECTION

1916
01:10:51,160 --> 01:10:52,840
HAPPENING SIMILAR LEVEL BUT WHAT

1917
01:10:52,840 --> 01:10:56,200
IS STRIKING HERE, I PUT TOGETHER

1918
01:10:56,200 --> 01:10:57,120
THESE -- WE HAVE NOT SEEN THE

1919
01:10:57,120 --> 01:10:59,440
SPIKES AND UPS AND DOWNS SO

1920
01:10:59,440 --> 01:11:02,400
REALLY VERY STABLE AT THIS

1921
01:11:02,400 --> 01:11:03,120
STAGE.

1922
01:11:03,120 --> 01:11:05,040
THIS IS WHERE ALL (INAUDIBLE)

1923
01:11:05,040 --> 01:11:06,480
NOW WE ASKED THE QUESTION, WHAT

1924
01:11:06,480 --> 01:11:09,280
ABOUT THESE PEOPLE WHO ARE

1925
01:11:09,280 --> 01:11:13,480
INFECTED, TWO QUESTIONS, ONE, IS

1926
01:11:13,480 --> 01:11:15,840
THERE ANY CHANGE IN REACTING, IN

1927
01:11:15,840 --> 01:11:18,800
OTHER WORDS DOES ANY SARS COV-2

1928
01:11:18,800 --> 01:11:20,440
ANTIBODY CROSS REACT WITH THESE,

1929
01:11:20,440 --> 01:11:26,360
YOU THINK OF THAT IN THIS -- SO

1930
01:11:26,360 --> 01:11:29,040
WITH THE ALPHA VIRUSES, REALLY

1931
01:11:29,040 --> 01:11:32,800
BE -- DON'T PICK UP MUCH, THE

1932
01:11:32,800 --> 01:11:33,920
ALPHA CORONA VIRUS BUT NOW YOU

1933
01:11:33,920 --> 01:11:37,720
SEE THE BLACK LINES BEFORE 51

1934
01:11:37,720 --> 01:11:41,440
BLACK LINES NOW YOU HAVE 270

1935
01:11:41,440 --> 01:11:44,680
BLACK LINES SO REMARKABLE

1936
01:11:44,680 --> 01:11:50,520
STABILITY OF THE ANTIBODY, AGAIN

1937
01:11:50,520 --> 01:11:53,400
NOT MUCH (INAUDIBLE) HAPPENING.

1938
01:11:53,400 --> 01:11:55,600
BUT WITH THE TWO BETA CORONA

1939
01:11:55,600 --> 01:12:02,440
VIRUS WE DO SEE ESPECIALLY

1940
01:12:02,440 --> 01:12:03,080
DEFINITELY SEEING SON ANTIBODY

1941
01:12:03,080 --> 01:12:06,840
USED BY THIS ASSAY TO INFECTION

1942
01:12:06,840 --> 01:12:08,240
CROSS REACTIVE BECAUSE NOW YOU

1943
01:12:08,240 --> 01:12:10,560
SEE THIS HAS GONE UP, NOW THERE

1944
01:12:10,560 --> 01:12:13,400
A DECLINE BECAUSE THIS IS

1945
01:12:13,400 --> 01:12:16,160
(INAUDIBLE) CROSS REACTING AND

1946
01:12:16,160 --> 01:12:19,640
DECLINING SO MANY OF THE TIMES

1947
01:12:19,640 --> 01:12:23,120
NOW DECLINE IN THIS BLUE LINE

1948
01:12:23,120 --> 01:12:23,800
INFECTED.

1949
01:12:23,800 --> 01:12:28,160
AND LITTLE MORE STRIKING WITH

1950
01:12:28,160 --> 01:12:28,640
THE REACTIVITY.

1951
01:12:28,640 --> 01:12:31,720
WE HAVE ALSO EXTENDED THIS NOW

1952
01:12:31,720 --> 01:12:33,560
TO FURTHER YOU CAN SEE THE SAME

1953
01:12:33,560 --> 01:12:36,840
PATTERN YOU GO OUT 40 DAYS BLACK

1954
01:12:36,840 --> 01:12:40,120
LINES WILL CONTINUE, NOW

1955
01:12:40,120 --> 01:12:43,800
BECOMING MORE FLATTER AS THIS

1956
01:12:43,800 --> 01:12:45,800
SARS ANTIBODIES (INAUDIBLE) SO

1957
01:12:45,800 --> 01:12:48,120
LET ME CONCLUDE BY MAKING TWO

1958
01:12:48,120 --> 01:12:49,040
POINTS.

1959
01:12:49,040 --> 01:12:53,120
FIRST IS THAT THE INFECTION IS

1960
01:12:53,120 --> 01:12:55,400
ELICITING A VERY DURABLE

1961
01:12:55,400 --> 01:12:57,200
ANTIBODY RESPONSE TO SPIKE

1962
01:12:57,200 --> 01:12:57,840
PROTEINS.

1963
01:12:57,840 --> 01:13:00,880
AND IS REALLY NOT FLATTENED OUT

1964
01:13:00,880 --> 01:13:05,520
AND GIVING US HALF LIFE AS LONG

1965
01:13:05,520 --> 01:13:07,840
AS (INAUDIBLE) SO ONE OF THE BIG

1966
01:13:07,840 --> 01:13:09,240
QUESTIONS HERE IS WHAT -- THIS

1967
01:13:09,240 --> 01:13:11,480
IS ALREADY BEEN ADDRESSED BY

1968
01:13:11,480 --> 01:13:13,280
SOME OF THE SPEAKERS WHAT IS

1969
01:13:13,280 --> 01:13:14,360
DURABILITY AFTER INFECTION

1970
01:13:14,360 --> 01:13:15,640
VERSUS VACCINATION.

1971
01:13:15,640 --> 01:13:17,200
I THINK THIS WOULD BE A GREAT

1972
01:13:17,200 --> 01:13:19,240
TOPIC FOR DISCUSSION WHEN WE

1973
01:13:19,240 --> 01:13:20,320
HAVE SOME DISCUSSION TIME AND

1974
01:13:20,320 --> 01:13:22,640
THEN THE SECOND POINT IS THAT

1975
01:13:22,640 --> 01:13:25,880
THE RESPONSES TO THE ENDEMIC

1976
01:13:25,880 --> 01:13:27,680
CORONA VIRUS, STABLE OVER TIME,

1977
01:13:27,680 --> 01:13:29,960
INFECTIONS ACQUIRED OVER THE

1978
01:13:29,960 --> 01:13:32,360
GIVEN TITER AND THE QUESTION IS,

1979
01:13:32,360 --> 01:13:34,000
WHAT ABOUT PROTECTIVE IMMUNITY,

1980
01:13:34,000 --> 01:13:36,840
IS THERE SOME REINFECTION, THAT

1981
01:13:36,840 --> 01:13:42,920
PAPER IS DOCUMENTED (INAUDIBLE)

1982
01:13:42,920 --> 01:13:44,880
BUT HOW -- POPULATION TO LOOK AT

1983
01:13:44,880 --> 01:13:46,320
AND IS THERE SOME CLINICAL

1984
01:13:46,320 --> 01:13:48,320
INFECTION THAT BOOSTING A BIT IS

1985
01:13:48,320 --> 01:13:49,000
SOMETHING THAT COULD BE

1986
01:13:49,000 --> 01:13:50,960
HAPPENING BUT IN OUR COHORT, WE

1987
01:13:50,960 --> 01:13:53,360
DON'T SEE UPS AN DOWNS IN THE

1988
01:13:53,360 --> 01:13:53,760
ANTIBODY.

1989
01:13:53,760 --> 01:13:57,280
SO IF THERE IS REINFECTION AT

1990
01:13:57,280 --> 01:14:00,240
LEAST IN THIS COHORT BOOSTING

1991
01:14:00,240 --> 01:14:01,840
(INAUDIBLE) SO LET ME END HERE

1992
01:14:01,840 --> 01:14:03,480
ACTINOLENGING THE PEOPLE WHO DID

1993
01:14:03,480 --> 01:14:04,640
THIS WORK -- ACKNOWLEDGING THE

1994
01:14:04,640 --> 01:14:07,960
PEOPLE WHO DID THIS WORK.

1995
01:14:07,960 --> 01:14:13,440
SUSIE IN MY LAB LEADING TH
LEADING THE

1996
01:14:13,440 --> 01:14:17,120
STUDIES IN THE LAB.

1997
01:14:17,120 --> 01:14:17,960
ASSAY, IN PARTICULAR (INAUDIBLE)

1998
01:14:17,960 --> 01:14:21,840
WHO DID THE -- WHO HEADED THE

1999
01:14:21,840 --> 01:14:27,800
CLINICAL COHORT, VACCINE CENTER,

2000
01:14:27,800 --> 01:14:31,920
(INAUDIBLE) AND SACKAL ANALYSIS.

2001
01:14:31,920 --> 01:14:32,400
GRATEFUL COLLABORATION

2002
01:14:32,400 --> 01:14:34,640
(INAUDIBLE).

2003
01:14:34,640 --> 01:14:37,880
I WANT TO ACKNOWLEDGE FUNDING

2004
01:14:37,880 --> 01:14:39,440
FROM NIH, NIAID AND IN

2005
01:14:39,440 --> 01:14:42,640
PARTICULAR THE WONDERFUL CCHI

2006
01:14:42,640 --> 01:14:45,520
SUPPLEMENTAL FUNDING.

2007
01:14:45,520 --> 01:14:48,080
THANK YOU VERY MUCH.

2008
01:14:48,080 --> 01:14:49,240
>> THANK YOU, RAFI.

2009
01:14:49,240 --> 01:14:51,920
THANKS SO MUCH.

2010
01:14:51,920 --> 01:14:52,880
YOU HAVE A QUESTION?

2011
01:14:52,880 --> 01:14:54,680
>> YES.

2012
01:14:54,680 --> 01:14:56,480
THANK YOU VERY MUCH, RAFI, FOR

2013
01:14:56,480 --> 01:14:57,640
THAT PRESENTATION.

2014
01:14:57,640 --> 01:14:59,040
SO IN YOUR OPINION, AND THERE

2015
01:14:59,040 --> 01:15:02,320
HAVE BEEN A FEW PUBLICATIONS, TO

2016
01:15:02,320 --> 01:15:06,440
WHAT EXTENT DOES THIS

2017
01:15:06,440 --> 01:15:07,120
PRE-EXISTING IMMUNITY AGAINST

2018
01:15:07,120 --> 01:15:09,240
MAYBE CROSS REACTIVE ENDEMIC

2019
01:15:09,240 --> 01:15:11,840
CORONA VIRUSES PROVIDE

2020
01:15:11,840 --> 01:15:13,920
PROTECTION SUCH THAT WE HAVE A

2021
01:15:13,920 --> 01:15:16,280
LARGER POPULATION REALLY THIS

2022
01:15:16,280 --> 01:15:18,120
MILDER TO MORE MILD MODERATE

2023
01:15:18,120 --> 01:15:20,440
INFECTION THAT WE SEE IS CAN BE

2024
01:15:20,440 --> 01:15:23,360
ATTRIBUTED TO THAT.

2025
01:15:23,360 --> 01:15:27,040
>> WE HAVEN'T INVESTED IN THE

2026
01:15:27,040 --> 01:15:29,080
DISCUSSION TIME, I WOULD PREFER

2027
01:15:29,080 --> 01:15:30,640
TO' ON THAT, WE LOOKED AT THIS

2028
01:15:30,640 --> 01:15:31,840
ISSUE MORE DETAIL.

2029
01:15:31,840 --> 01:15:37,920
IN TERMS OF HOW SOME (INAUDIBLE)

2030
01:15:37,920 --> 01:15:40,440
BUT MY MORE BROADER -- IN TERMS

2031
01:15:40,440 --> 01:15:44,480
OF ANTIBODY RESPONSE, TO THE

2032
01:15:44,480 --> 01:15:47,000
ENDEMIC CORONA VIRUS, I DON'T

2033
01:15:47,000 --> 01:15:49,560
THINK THEY ARE (INAUDIBLE) THAT

2034
01:15:49,560 --> 01:15:53,000
WOULD BE MY POSITION.

2035
01:15:53,000 --> 01:15:55,240
>> THANK YOU.

2036
01:15:55,240 --> 01:15:57,160
ROSS KEDL.

2037
01:15:57,160 --> 01:15:59,240
>> RAFI, WHEN YOU LOOK AT THAT

2038
01:15:59,240 --> 01:16:00,600
-- WE HAVE SEEN THE SAME THING

2039
01:16:00,600 --> 01:16:03,840
WITH OC 43, THAT THAT PARTICULAR

2040
01:16:03,840 --> 01:16:06,680
SEASONAL STRAIN HAS A BETTER

2041
01:16:06,680 --> 01:16:07,920
CROSS REACTIVITY, (INAUDIBLE)

2042
01:16:07,920 --> 01:16:10,320
HAD A PAPER A WHILE AGO LOOK AT

2043
01:16:10,320 --> 01:16:11,080
HOSPITALIZED INDIVIDUALS AND

2044
01:16:11,080 --> 01:16:14,640
PEOPLE WHO HAD A PRE-EXISTING 43

2045
01:16:14,640 --> 01:16:16,240
RESPONSE HAD LOWER SYMPTOMS AN

2046
01:16:16,240 --> 01:16:17,040
LESS RISK.

2047
01:16:17,040 --> 01:16:17,960
>> YES.

2048
01:16:17,960 --> 01:16:20,600
SOMEBODY WAS RECENTLY INFECTED,

2049
01:16:20,600 --> 01:16:23,880
HAD A MODERATE ANTIBODY OR WAS

2050
01:16:23,880 --> 01:16:26,240
IN THAT HAD VERY HIGH, THAT IS

2051
01:16:26,240 --> 01:16:26,640
POSSIBLE.

2052
01:16:26,640 --> 01:16:27,600
>> AND SHE TRACKED IT DOWN AND

2053
01:16:27,600 --> 01:16:29,800
WE HAVE SEEN THE SAME THING THE

2054
01:16:29,800 --> 01:16:31,320
S 2 DOMAIN SEEMS TO BE THE PART

2055
01:16:31,320 --> 01:16:33,480
THAT SHARED MORE CLOSELY WITH

2056
01:16:33,480 --> 01:16:33,840
SARS COV-2.

2057
01:16:33,840 --> 01:16:37,240
HAVE YOU BROKEN DOWN TO S 1, S

2058
01:16:37,240 --> 01:16:37,680
2?

2059
01:16:37,680 --> 01:16:40,720
>> WE HAVEN'T AND WE HAVE

2060
01:16:40,720 --> 01:16:41,160
UTILIZATION.

2061
01:16:41,160 --> 01:16:45,120
WE HAVEN'T LOOKED AT THOSE CROSS

2062
01:16:45,120 --> 01:16:46,320
REACTIVE ANTIBODIES WHETHER THEY

2063
01:16:46,320 --> 01:16:47,720
ARE NEUTRALIZED OR NOT.

2064
01:16:47,720 --> 01:16:48,600
THOSE QUESTIONS NEED TO BE

2065
01:16:48,600 --> 01:16:51,280
ADDRESSED.

2066
01:16:51,280 --> 01:16:54,400
>> I'M WONDERING, RAFI, HOW MANY

2067
01:16:54,400 --> 01:16:55,840
MORE YEARS YOU THINK OF SARS

2068
01:16:55,840 --> 01:16:57,600
COV-2 INFECTION TO GET THOSE

2069
01:16:57,600 --> 01:16:59,440
FLAT LINE ANTIBODY RESPONSES?

2070
01:16:59,440 --> 01:17:00,920
HOW MANY MORE EXPOSURES DO YOU

2071
01:17:00,920 --> 01:17:05,520
THINK WE NEED?

2072
01:17:05,520 --> 01:17:08,840
>> I'M GETTING BOOSTED NOW SO

2073
01:17:08,840 --> 01:17:10,200
YOU MAY NEVER GET AN ANSWER TO

2074
01:17:10,200 --> 01:17:11,240
THAT QUESTION BUT IT IS

2075
01:17:11,240 --> 01:17:13,040
FLATTENING OUT REALLY NICELY.

2076
01:17:13,040 --> 01:17:16,040
YOU ARE NOW GETTING HALF LIFE OF

2077
01:17:16,040 --> 01:17:17,840
1,000 LOOKING AT THE COHORT

2078
01:17:17,840 --> 01:17:22,320
(INAUDIBLE) WE HAVE A STUDY THAT

2079
01:17:22,320 --> 01:17:25,160
INFLUENZA VACCINE STUDY WHERE WE

2080
01:17:25,160 --> 01:17:27,040
STARTED WITH ADJUVANT -- WE HAVE

2081
01:17:27,040 --> 01:17:29,080
BEEN FOLLOWING OUT TO SIX YEARS,

2082
01:17:29,080 --> 01:17:32,640
AND THIS PARTICULAR STUDY EACH

2083
01:17:32,640 --> 01:17:36,680
ADJUVANT AT H 5N 1 SO NO

2084
01:17:36,680 --> 01:17:37,560
EXPOSURE TO H 5.

2085
01:17:37,560 --> 01:17:40,000
THERE WE ARE SEEING A FLATTENING

2086
01:17:40,000 --> 01:17:41,960
OUT ABOUT -- BETWEEN -- WE HAD

2087
01:17:41,960 --> 01:17:43,840
ONE YEAR SAMPLE AND FIVE YEAR.

2088
01:17:43,840 --> 01:17:46,520
WE DIDN'T HAVE -- WE HAD BETWEEN

2089
01:17:46,520 --> 01:17:48,480
-- BETWEEN FIVE AND SIX YEAR

2090
01:17:48,480 --> 01:17:50,520
FLATTENED OUT BEAUTIFULLY.

2091
01:17:50,520 --> 01:17:51,600
>> GOOD.

2092
01:17:51,600 --> 01:17:52,440
OKAY.

2093
01:17:52,440 --> 01:17:53,240
ALL RIGHT.

2094
01:17:53,240 --> 01:17:56,160
I GUESS WE'LL GO TO THE NEXT

2095
01:17:56,160 --> 01:17:58,920
SPEAKER.

2096
01:17:58,920 --> 01:18:02,800
MY TURN TO INTRODUCE.

2097
01:18:02,800 --> 01:18:05,880
>> JULIE WILL TELL YOU PRESENT

2098
01:18:05,880 --> 01:18:08,680
ON CELLULAR RESPONSES IN THE

2099
01:18:08,680 --> 01:18:09,400
SAME POOL.

2100
01:18:09,400 --> 01:18:10,160
JUDY, ALL YOURS.

2101
01:18:10,160 --> 01:18:10,880
>> OKAY.

2102
01:18:10,880 --> 01:18:12,040
THANK YOU.

2103
01:18:12,040 --> 01:18:12,600
-- JULIE.

2104
01:18:12,600 --> 01:18:14,440
THANK YOU.

2105
01:18:14,440 --> 01:18:20,880
>> THANK YOU.

2106
01:18:20,880 --> 01:18:21,280
OKAY.

2107
01:18:21,280 --> 01:18:23,840
I WOULD LIKE TO THANK THE

2108
01:18:23,840 --> 01:18:26,240
ORGANIZERS FOR INVITING ME TO

2109
01:18:26,240 --> 01:18:27,200
SPEAK TODAY.

2110
01:18:27,200 --> 01:18:28,680
AND LET ME MAKE SURE I'M

2111
01:18:28,680 --> 01:18:34,000
STARTING AT THE BEGINNING HERE.

2112
01:18:34,000 --> 01:18:35,520
SO I WANTED TO TALK TO YOU ABOUT

2113
01:18:35,520 --> 01:18:40,240
A SELECTED PART OF THE LAST TWO

2114
01:18:40,240 --> 01:18:40,680
YEARS.

2115
01:18:40,680 --> 01:18:42,600
OUR TIME WITH COVID, IT IS VERY

2116
01:18:42,600 --> 01:18:45,480
CLEAR EARLY ON THAT IF WE WERE

2117
01:18:45,480 --> 01:18:47,160
TO TRY TO UNDERSTAND ANYTHING

2118
01:18:47,160 --> 01:18:53,440
ABOUT THIS VIRUS WE NEEDED TO DO

2119
01:18:53,440 --> 01:18:55,800
THIS IN NATURAL HISTORY COHORT

2120
01:18:55,800 --> 01:18:56,960
WITH SARS COV-2 INFECTION.

2121
01:18:56,960 --> 01:18:58,560
THE IDEA WOULD BE TO TRY TO LOOK

2122
01:18:58,560 --> 01:19:00,440
AT THE LONG TERM IMMUNE

2123
01:19:00,440 --> 01:19:02,800
RESPONSES ASSOCIATED WITH

2124
01:19:02,800 --> 01:19:04,600
CONTROL OF COVID-19.

2125
01:19:04,600 --> 01:19:08,520
THEN TO BE ABLE TO IMPLY THOSE

2126
01:19:08,520 --> 01:19:11,040
INSIGHTS INTO TESTING VACCINE

2127
01:19:11,040 --> 01:19:13,920
CANDIDATES TO ACCELERATE VACCINE

2128
01:19:13,920 --> 01:19:14,520
DEVELOPMENT.

2129
01:19:14,520 --> 01:19:16,280
OBVIOUSLY WE KNOW AT THIS POINT

2130
01:19:16,280 --> 01:19:19,640
THAT THE NATURAL HISTORY OF THIS

2131
01:19:19,640 --> 01:19:22,640
INFECTION IS NOW QUITE

2132
01:19:22,640 --> 01:19:23,760
HETEROGENOUS THING AS PEOPLE ARE

2133
01:19:23,760 --> 01:19:28,000
GETTING VACCINATED AND THEY GET

2134
01:19:28,000 --> 01:19:30,000
REINFECTED, OR GET VACCINATED

2135
01:19:30,000 --> 01:19:31,800
THEN GET BREAK THROUGH

2136
01:19:31,800 --> 01:19:32,120
INFECTION.

2137
01:19:32,120 --> 01:19:34,080
BUT CLEARLY I THINK THAT BETWEEN

2138
01:19:34,080 --> 01:19:37,760
OUR COHORTS, IN ATLANTA, WITH

2139
01:19:37,760 --> 01:19:39,680
RAFI AND ONES HERE IN SEATTLE,

2140
01:19:39,680 --> 01:19:42,120
WE STILL HAVE A GROUP THAT IS

2141
01:19:42,120 --> 01:19:43,640
STABLE NOT GETTING VACCINATED

2142
01:19:43,640 --> 01:19:46,080
AND WE HOPE THAT OVER TIME WE

2143
01:19:46,080 --> 01:19:49,320
CAN CONTINUE TO FOLLOW THAT MORE

2144
01:19:49,320 --> 01:19:52,200
CLEAN GROUP IN A SENSE.

2145
01:19:52,200 --> 01:19:56,240
SO REALLY IN ORDER TO BE ABLE TO

2146
01:19:56,240 --> 01:19:58,440
IDENTIFY CELLULAR RESPONSES, IN

2147
01:19:58,440 --> 01:20:00,560
A WAY THAT WE COULD COMPARE ONE

2148
01:20:00,560 --> 01:20:03,840
VACCINE CANDIDATE WITH ANOTHER,

2149
01:20:03,840 --> 01:20:06,440
WITH NATURAL INFECTION WE

2150
01:20:06,440 --> 01:20:10,000
DEVELOPED A VALUE DATED ASSAY

2151
01:20:10,000 --> 01:20:15,200
USING ULTRA GRAM REVERSE

2152
01:20:15,200 --> 01:20:16,120
CYTOMETRY.

2153
01:20:16,120 --> 01:20:19,760
WE VALIDATED THE ABILITY TO BE

2154
01:20:19,760 --> 01:20:23,400
ABLE TO QUANTIFY TH 1 AND TH 2

2155
01:20:23,400 --> 01:20:25,360
CD4 T-CELLS RESPONSES AND CD8

2156
01:20:25,360 --> 01:20:27,120
T-CELLS RESPONSES.

2157
01:20:27,120 --> 01:20:29,240
THAT WERE ANTIGEN SPECIFIC.

2158
01:20:29,240 --> 01:20:31,400
AND IN ORDER TO DO THAT

2159
01:20:31,400 --> 01:20:32,240
VALIDATION, THERE ARE FIVE

2160
01:20:32,240 --> 01:20:34,440
PARAMETERS WE DO AS LISTED HERE,

2161
01:20:34,440 --> 01:20:37,920
I WILL BRIEFLY SHOW YOU A LITTLE

2162
01:20:37,920 --> 01:20:40,000
BIT ABOUT JUST PICK LINEARITY

2163
01:20:40,000 --> 01:20:41,440
AND SHOW YOU HOW IT PERFORMS.

2164
01:20:41,440 --> 01:20:45,200
WE HAVE ALSO LOOKED AT THE

2165
01:20:45,200 --> 01:20:47,440
SPECIFICITIES BY GENE EPITOPE

2166
01:20:47,440 --> 01:20:50,440
MAPPING IN NOW LOOKING MORE BY

2167
01:20:50,440 --> 01:20:51,520
VARIANTS OF CONCERN.

2168
01:20:51,520 --> 01:20:53,000
AS WELL AS MEMORY AND

2169
01:20:53,000 --> 01:20:55,600
MULTI-FUNCTIONAL PHENOTYPES.

2170
01:20:55,600 --> 01:20:57,360
IN ADDITION WE DEVELOPED

2171
01:20:57,360 --> 01:20:59,000
STANDARDIZE ASSAYS TO PROTECT

2172
01:20:59,000 --> 01:21:02,040
THE FREQUENCIES OF SPIKE AND ARE

2173
01:21:02,040 --> 01:21:05,000
REALLY SPECIFIC B CELLS THAT IGG

2174
01:21:05,000 --> 01:21:09,480
IGM OR IGA THAT ARE CIRCULATING.

2175
01:21:09,480 --> 01:21:12,240
SO THIS IS THE PANEL FOR FLOW

2176
01:21:12,240 --> 01:21:13,800
CYTOMETRY THAT WE HAVE USED AND

2177
01:21:13,800 --> 01:21:15,320
THOSE MARKERS THAT ARE

2178
01:21:15,320 --> 01:21:17,000
HIGHLIGHTED ARE THE ONES THAT WE

2179
01:21:17,000 --> 01:21:19,320
REALLY FOCUS THE VALIDATION ON.

2180
01:21:19,320 --> 01:21:22,440
THEN IN ADDITION WE HAVE OTHER

2181
01:21:22,440 --> 01:21:24,120
FUNCTIONAL MARKERS, THAT WE ARE

2182
01:21:24,120 --> 01:21:26,680
ABLE TO ADD TO THAT AND

2183
01:21:26,680 --> 01:21:29,080
CHARACTERIZING MORE

2184
01:21:29,080 --> 01:21:32,880
COMPREHENSIVELY THE CELL

2185
01:21:32,880 --> 01:21:33,360
FUNCTIONS.

2186
01:21:33,360 --> 01:21:36,360
JUST POINT OUT TO YOU, THESE ARE

2187
01:21:36,360 --> 01:21:38,440
EXVIVO ASSAY, THEY ARE NOT LONG

2188
01:21:38,440 --> 01:21:40,360
TERM STIMULATION, THEY ARE SHORT

2189
01:21:40,360 --> 01:21:43,640
TERM AROUND SIX HOURS.

2190
01:21:43,640 --> 01:21:45,920
WITH OVERLAPPING PEPTIDES

2191
01:21:45,920 --> 01:21:47,600
SPANNING THE SEQUENCE OF THE

2192
01:21:47,600 --> 01:21:50,520
GENE PRODUCT WE ARE LOOKING AT.

2193
01:21:50,520 --> 01:21:52,840
SO JUST TO SHOW YOU HERE EXAMPLE

2194
01:21:52,840 --> 01:21:55,480
OF THE LINEARITY OF THE RESPONSE

2195
01:21:55,480 --> 01:21:57,600
AS WE ARE VALIDATING IT, YOU CAN

2196
01:21:57,600 --> 01:22:00,240
SEE THESE TH 1 RESPONSES TO

2197
01:22:00,240 --> 01:22:03,120
GAMMA INTERFERON AND/OR IL 2 FOR

2198
01:22:03,120 --> 01:22:06,080
S 1 AND S 2 AND THE CD8 RESPONSE

2199
01:22:06,080 --> 01:22:10,800
FOR THE SAME S 1 AND S 2.  THESE

2200
01:22:10,800 --> 01:22:14,120
ARE DIFFERENT DONORS BY CD4 OR

2201
01:22:14,120 --> 01:22:14,520
CD8.

2202
01:22:14,520 --> 01:22:15,880
THEN THESE ARE RESPONSES THAT WE

2203
01:22:15,880 --> 01:22:18,480
ARE SEEING FOR TH 2.

2204
01:22:18,480 --> 01:22:21,240
THOSE RESPONSES VERY LOW IN

2205
01:22:21,240 --> 01:22:22,360
NATURAL INFECTION SO IT WAS

2206
01:22:22,360 --> 01:22:23,880
DIFFICULT TO FIND PEOPLE THAT

2207
01:22:23,880 --> 01:22:26,080
HAD REALLY HAD THOSE RESPONSES,

2208
01:22:26,080 --> 01:22:27,840
WE ARE BEGINNING TO PICK UP SOME

2209
01:22:27,840 --> 01:22:29,400
IN THE VACCINE GROUPS.

2210
01:22:29,400 --> 01:22:34,200
BUT HERE WE ARE USING IL 4 AND

2211
01:22:34,200 --> 01:22:37,640
CD 154, CD 40 LIGAND AS WELL AS

2212
01:22:37,640 --> 01:22:41,240
IL 5 IL 13 CD 40 LIGAND.

2213
01:22:41,240 --> 01:22:43,480
SO THESE ARE RESPONSES THAT WE

2214
01:22:43,480 --> 01:22:46,560
NOW FEEL WE CAN RELIABLY DETECT

2215
01:22:46,560 --> 01:22:49,640
FOLLOWING THE VALIDATION

2216
01:22:49,640 --> 01:22:50,160
PROCEDURES.

2217
01:22:50,160 --> 01:22:54,080
SO NOW TURNING TO THE COHORT,

2218
01:22:54,080 --> 01:22:57,080
REALLY VALUE OF BEING ABLE TO

2219
01:22:57,080 --> 01:23:00,880
COMBINE COHORTS HERE AT THE

2220
01:23:00,880 --> 01:23:04,120
HUTCH, THEY ARE FAIRLY SIMILAR

2221
01:23:04,120 --> 01:23:09,200
IN TERMS OF THE AGE GROUPS

2222
01:23:09,200 --> 01:23:11,400
MEDIAN AGE 45 YEARS, A LITTLE

2223
01:23:11,400 --> 01:23:14,640
BIT MORE FEMALE THAN MALE.

2224
01:23:14,640 --> 01:23:20,160
PREDOMINANTLY WHITE, 75% AND

2225
01:23:20,160 --> 01:23:21,600
THEN THEREAFTER SMALLER

2226
01:23:21,600 --> 01:23:24,320
PERCENTAGES OF OTHER RACE OR

2227
01:23:24,320 --> 01:23:24,880
ETHNIC GROUPS.

2228
01:23:24,880 --> 01:23:27,480
AS RAFI INDICATED THESE ARE

2229
01:23:27,480 --> 01:23:30,120
PRIMARILY MILD TO MODERATE

2230
01:23:30,120 --> 01:23:30,520
INFECTIONS.

2231
01:23:30,520 --> 01:23:33,440
THERE WERE A FEW THAT OVER TIME

2232
01:23:33,440 --> 01:23:35,280
WERE CATEGORIZED AS SEVERE.

2233
01:23:35,280 --> 01:23:37,560
AND THERE ARE A FEW THAT WE ARE

2234
01:23:37,560 --> 01:23:38,880
STILL CATCHING UP ON TO KNOW

2235
01:23:38,880 --> 01:23:41,360
EXACTLY HOW THEY ARE CLASSIFIED

2236
01:23:41,360 --> 01:23:42,160
OVER TIME.

2237
01:23:42,160 --> 01:23:44,880
I WILL NOTE THAT WE DO HAVE SOME

2238
01:23:44,880 --> 01:23:47,120
LONG HAULERS IN THIS GROUP THAT

2239
01:23:47,120 --> 01:23:51,680
WE ALSO HAVE BEEN ABLE TO FOLLOW

2240
01:23:51,680 --> 01:23:54,400
THIS -- IN THESE COHORT

2241
01:23:54,400 --> 01:23:54,800
LONGITUDINALLY.

2242
01:23:54,800 --> 01:24:00,200
IT IS RUNNING AT ABOUT 32% BY

2243
01:24:00,200 --> 01:24:00,600
STRICT DEFINITION.

2244
01:24:00,600 --> 01:24:04,520
SO HERE I WILL SHOW YOU

2245
01:24:04,520 --> 01:24:07,240
POLYFUNCTIONAL MEMORY CD4

2246
01:24:07,240 --> 01:24:10,880
T-CELLS, CD8 CELLS AND SPIKE

2247
01:24:10,880 --> 01:24:12,280
SPECIFIC A B CELLS.

2248
01:24:12,280 --> 01:24:16,200
JUST TO REMARK AFTER STUDYING

2249
01:24:16,200 --> 01:24:17,240
THESE OVER EIGHT MONTHS WE CAN

2250
01:24:17,240 --> 01:24:20,320
TELL YOU THEY ARE DURABLE.

2251
01:24:20,320 --> 01:24:22,600
AND THE HALF LIVES ARE SHOWN

2252
01:24:22,600 --> 01:24:25,000
HERE AROUND 200 DAYS BOTH CD4

2253
01:24:25,000 --> 01:24:27,840
AND CD8 T-CELLS AND FOR THE

2254
01:24:27,840 --> 01:24:30,880
MEMORY CELLS WE HAVEN'T SEEN

2255
01:24:30,880 --> 01:24:32,600
MUCH K OVER THE EIGHT MONTH

2256
01:24:32,600 --> 01:24:34,960
PERIOD, THEY ARE SLIGHTLY

2257
01:24:34,960 --> 01:24:37,120
BEGINNING -- THEY HAVE PLATEAUED

2258
01:24:37,120 --> 01:24:38,920
NOW AND FURTHER EVALUATION IS

2259
01:24:38,920 --> 01:24:42,200
ONGOING.

2260
01:24:42,200 --> 01:24:46,600
SO FOR THE CD4 RESPONSES USING

2261
01:24:46,600 --> 01:24:49,000
SIMILAR LONGITUDINAL PANELS AS

2262
01:24:49,000 --> 01:24:52,840
YOU SAW FROM RAFI, JUST NOTE THE

2263
01:24:52,840 --> 01:24:54,920
PROGRESSION OF THAT OVER TIME.

2264
01:24:54,920 --> 01:24:56,440
I THINK THE KEY THING TO NOTE IN

2265
01:24:56,440 --> 01:24:59,080
ALL THESE GRAPHSNA YOU WILL SEE

2266
01:24:59,080 --> 01:25:01,880
IS THAT CLEARLY ARE SOME

2267
01:25:01,880 --> 01:25:03,040
INDIVIDUAL WHOSE ARE NOT

2268
01:25:03,040 --> 01:25:04,000
RESPONSIBILITYING WELL OR THAT

2269
01:25:04,000 --> 01:25:05,320
THOSE RESPONSES -- RESPONDING

2270
01:25:05,320 --> 01:25:06,720
WELL OR THOSE RESPONSES GO AWAY.

2271
01:25:06,720 --> 01:25:08,560
HOWEVER THE MAJORITY ARE

2272
01:25:08,560 --> 01:25:11,640
RESISTANT AND THEY TEND TO PEAK

2273
01:25:11,640 --> 01:25:12,680
AROUND 30 DAYS.

2274
01:25:12,680 --> 01:25:16,560
WHAT IS IMPORTANT HERE ARE THE

2275
01:25:16,560 --> 01:25:17,480
TERMINATION'S OF SPECIFICITIES

2276
01:25:17,480 --> 01:25:19,920
OF THE RESPONSE FOR THE CD4

2277
01:25:19,920 --> 01:25:21,760
T-CELLS WE SAW THAT REALLY THERE

2278
01:25:21,760 --> 01:25:23,880
WAS PRETTY MUCH EQUAL TARGETING

2279
01:25:23,880 --> 01:25:25,560
ACROSS THE PROTEOME IN THESE ARE

2280
01:25:25,560 --> 01:25:29,360
JUST EXAMPLES THAT WE HAVE HERE

2281
01:25:29,360 --> 01:25:33,960
AS SHOWN FOR SPIKE ENVELOPE.

2282
01:25:33,960 --> 01:25:35,480
AND THE OTHER ONE SO THEY ALL

2283
01:25:35,480 --> 01:25:41,200
THE WAY ACROSS FAIRLY SIMILAR.

2284
01:25:41,200 --> 01:25:42,320
IN TERMS OF FREQUENCIES OF

2285
01:25:42,320 --> 01:25:43,320
RESPONSES AS WELL AS RESPONSE

2286
01:25:43,320 --> 01:25:48,120
RATES.  WE LOOKED AT THE

2287
01:25:48,120 --> 01:25:48,640
POLYFUNCTIONALTY OF THESE

2288
01:25:48,640 --> 01:25:53,640
RESPONSES USING THE MARKERS THAT

2289
01:25:53,640 --> 01:25:56,480
WERE IN ADDITION TO ONES I

2290
01:25:56,480 --> 01:25:58,640
DESCRIBED SO HERE THE ONES THAT

2291
01:25:58,640 --> 01:26:02,440
WERE REALLY CONTRIBUTING TO THE

2292
01:26:02,440 --> 01:26:04,440
MOST POSITIVE SUB POPULATIONS

2293
01:26:04,440 --> 01:26:06,960
ARE SHOWN HERE GAMMA INTERFERON,

2294
01:26:06,960 --> 01:26:11,920
IL 2 TNF ALPHA AND WITH CD 40

2295
01:26:11,920 --> 01:26:12,680
LIGAND IN GRANZYME B.

2296
01:26:12,680 --> 01:26:16,800
WE DIDN'T REALLY SEE PERFORIN

2297
01:26:16,800 --> 01:26:19,440
EXPRESSION WELL IN THIS GROUP BY

2298
01:26:19,440 --> 01:26:21,680
THIS TYPE OF ANALYSIS, BUT YOU

2299
01:26:21,680 --> 01:26:23,480
CAN SEE THAT DOMINANT

2300
01:26:23,480 --> 01:26:25,000
POPULATIONS ARE THOSE THAT

2301
01:26:25,000 --> 01:26:30,120
EXPRESS GAMMA IL 2 TNF ALPHA AND

2302
01:26:30,120 --> 01:26:35,240
CD 40 LIGAND.

2303
01:26:35,240 --> 01:26:41,320
THEN WE LOOK AT THESE BY U MAP

2304
01:26:41,320 --> 01:26:42,760
WITH US AND I THINK JUST TO

2305
01:26:42,760 --> 01:26:44,400
HIGHLIGHT THAT REALLY WE AREN'T

2306
01:26:44,400 --> 01:26:46,400
SEEING THE TH 2 RESPONSES IN

2307
01:26:46,400 --> 01:26:47,880
THIS GROUP AT ALL.

2308
01:26:47,880 --> 01:26:51,720
AND IT IS PREDOMINANTLY THE TH 1

2309
01:26:51,720 --> 01:26:53,240
RESPONSES.

2310
01:26:53,240 --> 01:26:54,120
THERE'S SOME OTHER INTERESTING

2311
01:26:54,120 --> 01:26:56,840
THINGS HERE WITH MORE TIME I

2312
01:26:56,840 --> 01:26:59,880
WILL GET TYPE THAT.

2313
01:26:59,880 --> 01:27:04,840
NOW FOR THE CD8 RESPONSE AGAIN A

2314
01:27:04,840 --> 01:27:06,840
SIMILAR K KINETICS OF PEAK

2315
01:27:06,840 --> 01:27:09,600
AROUND 30 DAYS AND THEN OTHER

2316
01:27:09,600 --> 01:27:10,880
FREQUENCIES TEND NOT TO BE AS

2317
01:27:10,880 --> 01:27:14,680
HIGH AS WHAT WE SAW WITH CD4

2318
01:27:14,680 --> 01:27:16,240
RESPONSES AND AGAIN CLEARLY

2319
01:27:16,240 --> 01:27:19,280
THERE ARE SOME THAT ARE NOT

2320
01:27:19,280 --> 01:27:20,240
RESPONDING OR THAT DROP OFF

2321
01:27:20,240 --> 01:27:20,640
EARLY.

2322
01:27:20,640 --> 01:27:23,440
IN TERMS OF SPECIFICITIES REAL

2323
01:27:23,440 --> 01:27:28,000
DIFFERENT PICTURE HERE, FOR

2324
01:27:28,000 --> 01:27:30,720
EPITOPE SPECIFICITY, HERE WE

2325
01:27:30,720 --> 01:27:32,960
PREDOMINANTLY SAW NUCLEAR CAPSID

2326
01:27:32,960 --> 01:27:36,000
RESPONSE IN THESE EXVIVO

2327
01:27:36,000 --> 01:27:38,880
STIMULATED CELLS, AND THIS TO ME

2328
01:27:38,880 --> 01:27:40,440
IS A REMARKABLE DIFFERENCE THAN

2329
01:27:40,440 --> 01:27:42,840
WHAT WE ARE SEEING IN THE CD4

2330
01:27:42,840 --> 01:27:43,280
RESPONSES.

2331
01:27:43,280 --> 01:27:45,040
WE WILL COME BACK TO THIS A BIT

2332
01:27:45,040 --> 01:27:50,520
LATER.

2333
01:27:50,520 --> 01:27:51,680
POLYFUNCTIONAL RESPONSES PICKING

2334
01:27:51,680 --> 01:27:54,480
UP PERFORIN IN THESE GROUPS

2335
01:27:54,480 --> 01:27:56,840
FAIRLY RELIABLY BUT THE

2336
01:27:56,840 --> 01:27:58,440
PREDOMINANT CYTOKINES ARE GAMMA

2337
01:27:58,440 --> 01:28:02,800
INTERFERON AND TNF ALPHA.

2338
01:28:02,800 --> 01:28:05,960
SO THE EVOLUTION OF THIS

2339
01:28:05,960 --> 01:28:07,840
RESPONSE LOOKING AT

2340
01:28:07,840 --> 01:28:09,360
MISDEMEANORRY RESPONSE, THE CD4

2341
01:28:09,360 --> 01:28:12,240
RESPONSE IS VERY RELIABLY

2342
01:28:12,240 --> 01:28:14,000
PREDOMINANTLY SIMPLE MEMORY

2343
01:28:14,000 --> 01:28:17,240
CELLS, EFFECTOR MEMORIES AND

2344
01:28:17,240 --> 01:28:18,760
VERY LOW RESPONSE BY CONTRAST

2345
01:28:18,760 --> 01:28:22,760
THE CD8 T-CELLS ARE

2346
01:28:22,760 --> 01:28:24,400
PREDOMINANTLY EFFECTOR CELLS,

2347
01:28:24,400 --> 01:28:25,840
MEMORY OR TUMOR RESPONSES YOU

2348
01:28:25,840 --> 01:28:28,320
CAN SEE HOW THEY BEGIN TO

2349
01:28:28,320 --> 01:28:29,640
INTERSECT OVER TIME.

2350
01:28:29,640 --> 01:28:34,560
WITH THE FAIRLY STABLE BUT LOWER

2351
01:28:34,560 --> 01:28:37,080
CENTRAL MEMORY POPULATION.

2352
01:28:37,080 --> 01:28:39,440
MOVING TO THE MEMORY B CELL

2353
01:28:39,440 --> 01:28:41,160
RESPONSES AS I EXPLAINED

2354
01:28:41,160 --> 01:28:43,280
EARLIER, REALLY DID NOT SEE A

2355
01:28:43,280 --> 01:28:46,560
DECAY OVER THIS 200 -- OF THE

2356
01:28:46,560 --> 01:28:51,240
250 DAYS, AS SHOWN HERE.

2357
01:28:51,240 --> 01:28:53,840
AND THESE DID PEAK 30 DAYS OR

2358
01:28:53,840 --> 01:28:56,400
GREATER IN THIS POPULATION.

2359
01:28:56,400 --> 01:28:57,840
OBVIOUSLY THE PREDOMINANT

2360
01:28:57,840 --> 01:29:03,640
RESPONSE AFTER THE FIRST MONTHS

2361
01:29:03,640 --> 01:29:06,120
IS IGG SHOWN HERE DROP OFF OF

2362
01:29:06,120 --> 01:29:13,840
IGM AND IGA.

2363
01:29:13,840 --> 01:29:15,160
TO SUMMARIZE IN CARTOON WE ARE

2364
01:29:15,160 --> 01:29:22,240
SEEING THE DROP OFF OR IGM B

2365
01:29:22,240 --> 01:29:23,560
CELLS PEAKING EARLY IN INFECTION

2366
01:29:23,560 --> 01:29:25,800
BUT THERE IS SUSTAINED IGG B

2367
01:29:25,800 --> 01:29:30,080
CELL RESPONSE, THIS IS TO BOTH

2368
01:29:30,080 --> 01:29:30,840
DETECTION OF THE SPIKE SPECIFIC

2369
01:29:30,840 --> 01:29:32,640
RESPONSES AS WELL AS RBD

2370
01:29:32,640 --> 01:29:35,400
SPECIFIC RESPONSES.

2371
01:29:35,400 --> 01:29:37,040
CD4 T-CELL FREAK SHIES ARE

2372
01:29:37,040 --> 01:29:40,200
HIGHER THAN THE CD8 T-CELL

2373
01:29:40,200 --> 01:29:43,680
FREQUENCY BUT THEY BOTH PEAK

2374
01:29:43,680 --> 01:29:45,320
AROUND DAY 30 AND PERSIST BUT

2375
01:29:45,320 --> 01:29:49,960
CONTINUE TO DECAY AFTER OUT TO A

2376
01:29:49,960 --> 01:29:53,840
YEAR.

2377
01:29:53,840 --> 01:29:56,440
WE HAVE HAD AS MANY OF YOU HAVE

2378
01:29:56,440 --> 01:30:00,160
ALREADY DISCUSSED, INDIVIDUALS

2379
01:30:00,160 --> 01:30:03,120
WHO NOW ACQUIRE SARS COV-2

2380
01:30:03,120 --> 01:30:04,680
INFECTION WHO WERE PREVIOUSLY

2381
01:30:04,680 --> 01:30:05,760
VACCINATED AND SO CALL IT BREAK

2382
01:30:05,760 --> 01:30:08,240
THROUGH INFECTION.

2383
01:30:08,240 --> 01:30:10,280
SO WE HAD OPPORTUNITY TO LOOK AT

2384
01:30:10,280 --> 01:30:14,840
38 OF THOSE THAT RECEIVED TWO

2385
01:30:14,840 --> 01:30:17,600
DOSE mRNA VACCINE, MOST WERE

2386
01:30:17,600 --> 01:30:18,960
PFIZER VACCINES AND SOME

2387
01:30:18,960 --> 01:30:21,120
MODERNA.

2388
01:30:21,120 --> 01:30:23,400
WHAT WE WERE INTERESTED IS HOW

2389
01:30:23,400 --> 01:30:28,640
DO THESE T-CELL RESPONSES DIFFER

2390
01:30:28,640 --> 01:30:31,840
IN QUALITY AND QUANTITY.

2391
01:30:31,840 --> 01:30:35,360
SO LOOKING AT THE CD4 T-CELL

2392
01:30:35,360 --> 01:30:38,520
RESPONSES, WE ARE LABELING

2393
01:30:38,520 --> 01:30:41,520
UNVACCINATED COHORT WE HAVE

2394
01:30:41,520 --> 01:30:44,520
DESCRIBEDDED THAT IS NOT

2395
01:30:44,520 --> 01:30:47,520
RECEIVED ANY VACCINE JUST

2396
01:30:47,520 --> 01:30:49,120
EXPOSED BY NATURAL INFECTION IN

2397
01:30:49,120 --> 01:30:52,000
CONTRAST TO BREAK THROUGH

2398
01:30:52,000 --> 01:30:55,800
INFECTION THAT'S RECEIVE TWO

2399
01:30:55,800 --> 01:30:57,360
DOSE OF mRNA VACCINE FOLLOWED

2400
01:30:57,360 --> 01:31:01,600
BY BREAK THROUGH INFECTION.

2401
01:31:01,600 --> 01:31:04,000
SO LET'S START WITH CD4, THESE

2402
01:31:04,000 --> 01:31:07,480
ARE TH 1 TYPE RESPONSE AGAINST

2403
01:31:07,480 --> 01:31:07,920
SPIKE.

2404
01:31:07,920 --> 01:31:11,400
OR AGAINST NON-SPIKE ANTIGENS

2405
01:31:11,400 --> 01:31:14,400
AND IT IS OBVIOUS AS YOU CAN

2406
01:31:14,400 --> 01:31:16,960
IMAGINE IN CONSISTENT FINDING IS

2407
01:31:16,960 --> 01:31:19,000
THAT THE SPIKE RESPONSES COME UP

2408
01:31:19,000 --> 01:31:22,160
VERY FAST CERTAINLY MUCH FASTER

2409
01:31:22,160 --> 01:31:23,400
THAN WHAT WE SEE IN NATURAL

2410
01:31:23,400 --> 01:31:23,960
INFECTION.

2411
01:31:23,960 --> 01:31:30,040
THEY ARE PERSISTING OUT TO 61

2412
01:31:30,040 --> 01:31:31,720
DAY, WE HAVEN'T SEEN QUITE AS

2413
01:31:31,720 --> 01:31:33,440
MANY PEOPLE AFTER 61 DAYS BUT

2414
01:31:33,440 --> 01:31:35,640
YOU CAN SEE THEY ARE QUITE

2415
01:31:35,640 --> 01:31:37,840
RESISTANT --ER PERSISTENT AND

2416
01:31:37,840 --> 01:31:38,960
HIGHER FREQUENCY THAN WHAT WE

2417
01:31:38,960 --> 01:31:41,440
SEE IN NATURAL INFECTION.

2418
01:31:41,440 --> 01:31:45,080
BY CONTRAST, THE NON-SPIKE

2419
01:31:45,080 --> 01:31:47,440
ANTIGENS WHICH AS YOU KNOW,

2420
01:31:47,440 --> 01:31:49,840
THESE ARE NOT IN THE VACCINES

2421
01:31:49,840 --> 01:31:53,240
THEY ARE RECEIVING, LOOK PAIRLY

2422
01:31:53,240 --> 01:31:54,280
SIMILAR BETWEEN TWO GROUPS AS

2423
01:31:54,280 --> 01:31:56,600
YOU SEE OVER TIME.

2424
01:31:56,600 --> 01:31:58,680
IF ANYTHING THOSE WITH THE

2425
01:31:58,680 --> 01:32:00,880
NATURAL INFECTION ARE SOMEWHAT

2426
01:32:00,880 --> 01:32:05,120
HIGHER.

2427
01:32:05,120 --> 01:32:08,000
SO LOOK AT THE CD8 RESPONSES

2428
01:32:08,000 --> 01:32:11,240
AGAIN IN THESE SAME TWO GROUPS.

2429
01:32:11,240 --> 01:32:12,880
STARTING WITH A SPIKE RESPONSE,

2430
01:32:12,880 --> 01:32:16,640
I THINK THAT THE THINGS YOU WILL

2431
01:32:16,640 --> 01:32:19,320
SEE HERE ARE OBVIOUSLY THE CD8

2432
01:32:19,320 --> 01:32:21,680
RESPONSES RECOGNIZING THE SPIKE

2433
01:32:21,680 --> 01:32:23,360
ANTIGENS ARE DEFINITELY HIGHER.

2434
01:32:23,360 --> 01:32:26,240
IN THE BREAK THROUGHS THAN THEY

2435
01:32:26,240 --> 01:32:30,240
ARE IN THOSE WITH NATURAL

2436
01:32:30,240 --> 01:32:31,240
INFECTION WITHOUT VACCINATION.

2437
01:32:31,240 --> 01:32:35,480
LIKE WE SAW THE CD4 RESPONSES

2438
01:32:35,480 --> 01:32:36,720
THEY ARE PERSISTING BUT

2439
01:32:36,720 --> 01:32:38,920
SITUATION IS DIFFERENT WITH THE

2440
01:32:38,920 --> 01:32:41,440
NON-SPIKE ANTIGENS OBVIOUSLY WE

2441
01:32:41,440 --> 01:32:46,440
ARE NOT -- WE ARE SEEING A

2442
01:32:46,440 --> 01:32:49,720
DELAYED RISE OF RESPONSES IN

2443
01:32:49,720 --> 01:32:51,240
BREAK THROUGH INFECTIONS.

2444
01:32:51,240 --> 01:32:54,240
AND ALSO POTENTIALLY SOME

2445
01:32:54,240 --> 01:32:55,320
INDICATION THAT THOSE MAY BE

2446
01:32:55,320 --> 01:32:57,800
LESS DURABLE IN THIS GROUP IN

2447
01:32:57,800 --> 01:32:59,440
CONTRAST TO WHAT WE SEE WITH

2448
01:32:59,440 --> 01:33:02,440
THOSE THAT FIRST WERE EXPOSED TO

2449
01:33:02,440 --> 01:33:05,040
SARS COV-2 BY NATURAL INFECTION.

2450
01:33:05,040 --> 01:33:09,200
SO THE KINETICS OF THIS OVER

2451
01:33:09,200 --> 01:33:11,200
TIME WILL BE REALLY IMPORTANT,

2452
01:33:11,200 --> 01:33:14,320
THAT SOMETHING WE PLAN TO DO

2453
01:33:14,320 --> 01:33:19,440
WITH BOTH ATLANTA AND -- COHORT.

2454
01:33:19,440 --> 01:33:23,240
JUST IN SUMMARY, CLEARLY A

2455
01:33:23,240 --> 01:33:24,480
PERSISTENT IMMUNOVIRAL MEMORY

2456
01:33:24,480 --> 01:33:28,200
RESPONSE IS INDUCED IN MILD

2457
01:33:28,200 --> 01:33:29,920
MODERATE COVID-19.

2458
01:33:29,920 --> 01:33:32,720
WE SEE CONTINUED RISE AND

2459
01:33:32,720 --> 01:33:34,240
PLATEAU DESPITE MEMORY B CELLS,

2460
01:33:34,240 --> 01:33:37,000
SLOW DECAY, CD8 T-CELLS BUT

2461
01:33:37,000 --> 01:33:38,880
DISTINCT FEATURES AMONG THEM

2462
01:33:38,880 --> 01:33:42,440
BROADER SPECIFICITIES AMONG CD4

2463
01:33:42,440 --> 01:33:43,760
T-CELLS AND MORE DOMINANT WITH

2464
01:33:43,760 --> 01:33:48,760
CAPSID RESPONSE IN CD8 T-CELLS.

2465
01:33:48,760 --> 01:33:50,000
THERE SHALL DISTINCT MEMORY SUB

2466
01:33:50,000 --> 01:33:54,400
POPULATIONS OVER TIME.

2467
01:33:54,400 --> 01:33:56,480
THE MARKED HETEROGENEITY OF

2468
01:33:56,480 --> 01:33:57,400
THESE RESPONSES IS VERY

2469
01:33:57,400 --> 01:34:00,360
IMPORTANT AND QUITE EASY TO SEE

2470
01:34:00,360 --> 01:34:01,240
LOOKING AT FREQUENCY AND

2471
01:34:01,240 --> 01:34:04,040
MAGNITUDE OF THE RESPONSE.

2472
01:34:04,040 --> 01:34:05,960
NOTABLY THERE ARE SOME

2473
01:34:05,960 --> 01:34:07,160
PERSISTENT NON-RESPONDERS.

2474
01:34:07,160 --> 01:34:10,200
IN OUR GROUP.

2475
01:34:10,200 --> 01:34:15,400
DESPITE MEMORY IMMUNE RESPONSES

2476
01:34:15,400 --> 01:34:18,760
ABOUT 30% SHOWING SYMPTOMS

2477
01:34:18,760 --> 01:34:20,600
CONSISTENT WITH TASK AFTER 60

2478
01:34:20,600 --> 01:34:21,640
DAYS.

2479
01:34:21,640 --> 01:34:23,040
OUR PRELIMINARY FINDINGS

2480
01:34:23,040 --> 01:34:24,760
COMPARING THE BREAK THROUGH

2481
01:34:24,760 --> 01:34:26,400
INFECTION WITH THE NATURAL

2482
01:34:26,400 --> 01:34:28,280
INFECTION IN THE UNVACCINATED

2483
01:34:28,280 --> 01:34:29,960
INDICATE THAT POTENTIALLY THE

2484
01:34:29,960 --> 01:34:31,840
KINETICS THE MAGNITUDE AND

2485
01:34:31,840 --> 01:34:34,200
DURABILITY OF THESE RESPONSES BE

2486
01:34:34,200 --> 01:34:34,640
DIFFERENT.

2487
01:34:34,640 --> 01:34:36,240
SO THAT IS SOMETHING THAT WE

2488
01:34:36,240 --> 01:34:38,040
PLAN TO LOOK AT MORE CAREFULLY

2489
01:34:38,040 --> 01:34:39,280
OVER TIME.

2490
01:34:39,280 --> 01:34:41,280
JUST LIKE TO ACKNOWLEDGE MY

2491
01:34:41,280 --> 01:34:44,560
GROUP HERE AT THE HUTCH AS WELL

2492
01:34:44,560 --> 01:34:46,840
AS REALLY THE NICE COLLABORATION

2493
01:34:46,840 --> 01:34:49,840
WE ARE HAVING WITH RAFI AND HIS

2494
01:34:49,840 --> 01:34:53,680
GROUP AS WELL AS OUR FUNDERS AT

2495
01:34:53,680 --> 01:34:55,600
PARTICULARLY TO DATE WHO HAS

2496
01:34:55,600 --> 01:34:58,240
BEEN SUPPORTIVE OF COHORT OF THE

2497
01:34:58,240 --> 01:35:01,440
STUDY AS WELL AS OTHER NIAID

2498
01:35:01,440 --> 01:35:04,000
DIVISION OF AIDS AND DMID WHO

2499
01:35:04,000 --> 01:35:04,600
FUND OUR VACCINE WORK.

2500
01:35:04,600 --> 01:35:09,320
SO I WILL STOP THERE.

2501
01:35:09,320 --> 01:35:10,000
>> THANK YOU.

2502
01:35:10,000 --> 01:35:16,200
QUESTIONS FOR JUDY PLEASE RAISE

2503
01:35:16,200 --> 01:35:19,760
YOUR HAND.

2504
01:35:19,760 --> 01:35:22,000
>> GO AHEAD.

2505
01:35:22,000 --> 01:35:24,040
WILL YOU THEN TO SHANE.

2506
01:35:24,040 --> 01:35:30,280
>> I HAVE A QUICK ONE.

2507
01:35:30,280 --> 01:35:32,640
KEY HOE'S GROUP EARLY IN THE

2508
01:35:32,640 --> 01:35:35,600
PANDEMIC REPORTED PRETTY HIGH TH

2509
01:35:35,600 --> 01:35:37,840
2 USE EXTRA FOLLICULAR RESPONSE

2510
01:35:37,840 --> 01:35:39,240
MANY IN SUBGROUP OF INFECTED

2511
01:35:39,240 --> 01:35:42,360
PEOPLE.

2512
01:35:42,360 --> 01:35:44,560
NOW, I DON'T -- MORE SEVERE

2513
01:35:44,560 --> 01:35:46,480
PATIENTS IN YOUR CASE IS MORE

2514
01:35:46,480 --> 01:35:47,520
MILD TO MODERATE.

2515
01:35:47,520 --> 01:35:50,080
COULD YOU COMMENT ONNA?

2516
01:35:50,080 --> 01:35:52,440
YOU DON'T SEEM TO SEE THE TH 2

2517
01:35:52,440 --> 01:35:54,920
RESPONSE.

2518
01:35:54,920 --> 01:35:56,840
>> I THINK IT IS IF WE WERE

2519
01:35:56,840 --> 01:35:58,320
GOING TO SEE THEM WE ARE NOT

2520
01:35:58,320 --> 01:35:59,360
PICKING THEM UP EARLY IN

2521
01:35:59,360 --> 01:36:02,120
INFECTION AND THROUGH THE

2522
01:36:02,120 --> 01:36:04,680
DURATION OF THAT WE HAVE LOOKED

2523
01:36:04,680 --> 01:36:07,200
AND I THINK IF ANYTHING IT MAY

2524
01:36:07,200 --> 01:36:09,840
BE RELATED TO SEVERITY OF

2525
01:36:09,840 --> 01:36:10,240
INFECTION.

2526
01:36:10,240 --> 01:36:12,880
BUT WE ARE JUST NOT SEEING IT.

2527
01:36:12,880 --> 01:36:15,000
WE ARE BEGINNING TO PICK SOME OF

2528
01:36:15,000 --> 01:36:17,240
THAT UP WITH THE VACCINES.

2529
01:36:17,240 --> 01:36:19,320
SO WE KNOW WE CAN DETECT THEM

2530
01:36:19,320 --> 01:36:21,800
BUT THEY JUST WEREN'T THERE.

2531
01:36:21,800 --> 01:36:24,480
>> THANK YOU.

2532
01:36:24,480 --> 01:36:27,640
>> WE DON'T REALLY SEE ANY TH

2533
01:36:27,640 --> 01:36:28,320
2s EITHER.

2534
01:36:28,320 --> 01:36:30,440
I BELIEVE THE DATA YOU ARE

2535
01:36:30,440 --> 01:36:31,880
REFERRING TO WAS POLYCLONAL

2536
01:36:31,880 --> 01:36:33,320
STIMULATION OF T-CELL.

2537
01:36:33,320 --> 01:36:35,280
NOT ACTUALLY SARS COV-2 PEPTIDES

2538
01:36:35,280 --> 01:36:36,360
AND I THINK A NUMBER OF PEOPLE

2539
01:36:36,360 --> 01:36:39,080
HAVE BEEN CONFUSED ABOUT THAT

2540
01:36:39,080 --> 01:36:42,840
TYPE OF DATA BUT I BELIEVE -- WE

2541
01:36:42,840 --> 01:36:45,680
LOOKED AT THESE DATA CLOSELY AND

2542
01:36:45,680 --> 01:36:48,840
JULIE'S LAB, OUR LAB, MARION'S

2543
01:36:48,840 --> 01:36:50,480
LAB AND SEVERAL OTHERS, SEE

2544
01:36:50,480 --> 01:36:53,400
MINIMAL ANTIGEN SPECIFIC TH 2s

2545
01:36:53,400 --> 01:36:55,280
OR TH 17.

2546
01:36:55,280 --> 01:36:56,840
BY SEVERAL DIFFERENT TYPES OF

2547
01:36:56,840 --> 01:36:59,360
ICS OR SECRETION ASSAYS.

2548
01:36:59,360 --> 01:37:00,720
IN THE CONTEXT OF NATURAL

2549
01:37:00,720 --> 01:37:09,600
INFECTION.

2550
01:37:09,600 --> 01:37:13,240
(OVERLAPPING SPEAKERS) BUT THE

2551
01:37:13,240 --> 01:37:16,240
QUESTION FOR JULIE WOULD BE IT

2552
01:37:16,240 --> 01:37:19,040
IS ABSOLUTELY BEAUTIFUL DATA AND

2553
01:37:19,040 --> 01:37:21,880
I MEAN YOUR EXTENSIVE VALIDATION

2554
01:37:21,880 --> 01:37:23,560
OF ASSAYS IS SO IMPRESSIVE.

2555
01:37:23,560 --> 01:37:25,240
OBVIOUSLY T-CELL HAS COMPLICATED

2556
01:37:25,240 --> 01:37:25,920
BECAUSE THERE IS A NUMBER OF

2557
01:37:25,920 --> 01:37:29,440
WAYS TO DO IT SO I HAVE HAD A

2558
01:37:29,440 --> 01:37:31,080
NUMBER OF PEOPLE RAISE TO ME THE

2559
01:37:31,080 --> 01:37:33,440
QUESTION IF T-CELL CAN'T MAKE

2560
01:37:33,440 --> 01:37:35,000
CYTOKINES IN SIX HOURS BUT IS

2561
01:37:35,000 --> 01:37:37,440
STILL ANTIGEN SPECIFIC, YOU MISS

2562
01:37:37,440 --> 01:37:39,040
IT, IS IT WORTH PAYING ATTENTION

2563
01:37:39,040 --> 01:37:39,560
TO.

2564
01:37:39,560 --> 01:37:41,840
AND I HAVE HAD PEOPLE ARGUE EVEN

2565
01:37:41,840 --> 01:37:44,040
FOR CD8, IF THEY HAVE MEMORY

2566
01:37:44,040 --> 01:37:46,320
CELLS THAT DON'T MAKE CYTOKINES

2567
01:37:46,320 --> 01:37:47,240
GROW FAST BUT THEY WOULD OVER

2568
01:37:47,240 --> 01:37:50,000
NIGHT OR PROLIFERATE, THEY WOULD

2569
01:37:50,000 --> 01:37:51,880
STILL BE WORTH COUNTING, HOW DO

2570
01:37:51,880 --> 01:37:55,000
YOU GUYS THINK ABOUT THAT FACTOR

2571
01:37:55,000 --> 01:37:55,960
T-CELL COMPLEXITY BECAUSE

2572
01:37:55,960 --> 01:37:57,240
OBVIOUSLY YOU GUYS ARE GREAT AT

2573
01:37:57,240 --> 01:37:59,000
THIS TYPE OF STUFF.

2574
01:37:59,000 --> 01:38:02,280
>> I THINK WE LOOKED AT THAT IN

2575
01:38:02,280 --> 01:38:03,400
THE PAST.

2576
01:38:03,400 --> 01:38:06,240
I THINK THAT THE KEY ISSUE FOR

2577
01:38:06,240 --> 01:38:08,880
US IS TO -- IF WE STIMULATE FOR

2578
01:38:08,880 --> 01:38:10,440
LONGER PERIODS OF TIME WHICH IS

2579
01:38:10,440 --> 01:38:11,600
STRAIGHT FORWARD TO DO AND

2580
01:38:11,600 --> 01:38:12,880
HONESTLY THE PEEP MILLION THE

2581
01:38:12,880 --> 01:38:18,000
LAB PREFER TO DO THAT SHORTER.

2582
01:38:18,000 --> 01:38:19,600
-- PEOPLE IN THE LAB PREFER TO

2583
01:38:19,600 --> 01:38:20,160
DO THAT.

2584
01:38:20,160 --> 01:38:26,440
BUT WE JUST DON'T GET THE DEPTH

2585
01:38:26,440 --> 01:38:30,400
OF -- WE TEND TO SEE MORE FALSE

2586
01:38:30,400 --> 01:38:32,920
POSITIVES IN THAT CASE.

2587
01:38:32,920 --> 01:38:37,400
AND IN OUR HANDS THESE CYTOKINE

2588
01:38:37,400 --> 01:38:40,160
MARKERS HAVE WELL CORRELATED

2589
01:38:40,160 --> 01:38:41,720
WITH PROLIFERATION WHEN WE

2590
01:38:41,720 --> 01:38:43,360
LOOKED AT THAT IN THE SAME

2591
01:38:43,360 --> 01:38:45,920
DONORS SO I'M NOT REALLY TOO

2592
01:38:45,920 --> 01:38:46,640
CONCERNED ABOUT THAT.

2593
01:38:46,640 --> 01:38:48,440
I KNOW IT COULD BE AN ISSUE.

2594
01:38:48,440 --> 01:38:50,640
WE ALSO ARE SEEING PERFORIN IN

2595
01:38:50,640 --> 01:38:52,080
THE CD8 T-CELLS.

2596
01:38:52,080 --> 01:38:55,080
I THINK THAT ONE MIGHT ARGUE

2597
01:38:55,080 --> 01:38:56,400
THAT THOSE ARE ONES THAT MIGHT

2598
01:38:56,400 --> 01:39:00,320
BE CAPABLE OF DOING MORE ANTS

2599
01:39:00,320 --> 01:39:04,720
VIRAL ACTIVITIES.

2600
01:39:04,720 --> 01:39:07,160
IT IS A WAY TO QUANTITATE

2601
01:39:07,160 --> 01:39:08,520
RESPONSE, IT IS A WAY WHEN WE

2602
01:39:08,520 --> 01:39:13,520
LOOK AT TETRAMERS WE SEE GOOD

2603
01:39:13,520 --> 01:39:16,840
CORRELATION SO I DON'T KNOW HOW

2604
01:39:16,840 --> 01:39:17,080
ELSE TO --

2605
01:39:17,080 --> 01:39:20,160
>> QUICK QUESTION AND QUICK --

2606
01:39:20,160 --> 01:39:22,240
>> MAYBE THIS IS -- YOU CAN --

2607
01:39:22,240 --> 01:39:23,840
IF THIS IS WORTHWHILE ANSWERING

2608
01:39:23,840 --> 01:39:26,120
MAYBE THE GROUP CAN ANSWER IT

2609
01:39:26,120 --> 01:39:28,000
LATER:  IT WAS A QUESTION OF IS

2610
01:39:28,000 --> 01:39:29,000
THERE BEEN MUCH EFFORT TO

2611
01:39:29,000 --> 01:39:32,640
COMPARE WHAT YOU SEE IN BLOOD IN

2612
01:39:32,640 --> 01:39:33,840
VACCINATION OR INFECTION WITH

2613
01:39:33,840 --> 01:39:37,120
WHAT YOU SEE IN THE TISSUE?

2614
01:39:37,120 --> 01:39:38,080
LUNG FOR EXAMPLE.

2615
01:39:38,080 --> 01:39:40,320
>> GREAT QUESTION.

2616
01:39:40,320 --> 01:39:43,840
WE ADDRESSED AT LEAST TO SOME

2617
01:39:43,840 --> 01:39:47,680
EXTENT BY DONNA.

2618
01:39:47,680 --> 01:39:51,640
AND LET'S LEAVE THAT FOR

2619
01:39:51,640 --> 01:39:52,360
DISCUSSION.

2620
01:39:52,360 --> 01:39:56,040
THE NEXT SPEAKER IS ROSS KEDL

2621
01:39:56,040 --> 01:39:58,000
FROM (INAUDIBLE) ROSS WILL TELL

2622
01:39:58,000 --> 01:40:00,800
US ABOUT ADJUVANT T-CELL

2623
01:40:00,800 --> 01:40:01,120
(INAUDIBLE).

2624
01:40:01,120 --> 01:40:02,000
ROSS.

2625
01:40:02,000 --> 01:40:04,240
>> CAN YOU GUYS HEAR ME?

2626
01:40:04,240 --> 01:40:04,880
>> YES.

2627
01:40:04,880 --> 01:40:07,960
>> IT IS AN INTERESTING QUESTION

2628
01:40:07,960 --> 01:40:09,560
FROM SHANE, THE IDEA OF

2629
01:40:09,560 --> 01:40:11,360
SELF-RENEWING POTENTIAL IS SUCH

2630
01:40:11,360 --> 01:40:12,480
A DIFFERENT -- THE CELLS THAT

2631
01:40:12,480 --> 01:40:13,720
MAKE THE MOST CYTOKINE TEND TO

2632
01:40:13,720 --> 01:40:15,920
BE THE ONES THAT ARE LESS -- AT

2633
01:40:15,920 --> 01:40:16,920
LEAST SELF-RENEWING.

2634
01:40:16,920 --> 01:40:20,200
AS PERTAINS TO THERAPEUTIC

2635
01:40:20,200 --> 01:40:21,200
T-CELL RESPONSES WHICH IS WHAT

2636
01:40:21,200 --> 01:40:22,840
I'M GOING TO TRY TO FOCUS ON

2637
01:40:22,840 --> 01:40:23,400
HERE.

2638
01:40:23,400 --> 01:40:25,800
THE ANSWERS TEND TO BE SORT OF

2639
01:40:25,800 --> 01:40:28,440
OPPOSITE OF THE BEST CELLS ARE

2640
01:40:28,440 --> 01:40:31,080
ONES OFTEN CYTOKINE RIGHT AWAY.

2641
01:40:31,080 --> 01:40:32,080
FIRST THANKS FOR THE OPPORTUNITY

2642
01:40:32,080 --> 01:40:35,440
TO PRESENT HERE.

2643
01:40:35,440 --> 01:40:37,280
THIS IS A GREAT GROUP OF PEOPLE

2644
01:40:37,280 --> 01:40:40,400
OF SPEAKERS TO BE INCLUDED IN

2645
01:40:40,400 --> 01:40:43,560
OUR -- AS I MENTION I'M GOING TO

2646
01:40:43,560 --> 01:40:45,600
EMPHASIZE THE IDEA OF ADJUVANT

2647
01:40:45,600 --> 01:40:47,000
ELICITED RESPONSES THAT ARE

2648
01:40:47,000 --> 01:40:47,960
TARGET TARGETING SPECIFICALLY

2649
01:40:47,960 --> 01:40:49,440
TRYING TO GENERATE AS LARGE

2650
01:40:49,440 --> 01:40:50,280
T-CELL RESPONSE AS POSSIBLE FOR

2651
01:40:50,280 --> 01:40:53,400
THE PURPOSES OF THERAPEUTIC

2652
01:40:53,400 --> 01:40:55,040
INTERVENTION.

2653
01:40:55,040 --> 01:40:57,160
WE HEARD ROBUST T-CELL RESPONSES

2654
01:40:57,160 --> 01:41:00,120
GENERATED BY VACCINES FOR SARS

2655
01:41:00,120 --> 01:41:06,800
COVID 2 AND HOW EFFICACIOUS AT

2656
01:41:06,800 --> 01:41:07,440
PREVENTING SIGNIFICANT DISEASE.

2657
01:41:07,440 --> 01:41:10,240
THE LEVEL OF THERAPEUTIC

2658
01:41:10,240 --> 01:41:11,760
INTERVENTION IN CHRONIC

2659
01:41:11,760 --> 01:41:13,320
INFECTIOUS SETTING OR CANCER

2660
01:41:13,320 --> 01:41:14,840
SETTING IS -- I'M GOING TO ARGUE

2661
01:41:14,840 --> 01:41:17,000
IS A SLIGHTLY DIFFERENT BAR.

2662
01:41:17,000 --> 01:41:18,640
SO THAT IS QUESTION I WILL BE

2663
01:41:18,640 --> 01:41:20,960
ADDRESSING HERE.

2664
01:41:20,960 --> 01:41:25,640
BEFORE I GET GOING, MOST OF YOU

2665
01:41:25,640 --> 01:41:29,240
HAVE IF YOU DON'T, MARKSATT PASS

2666
01:41:29,240 --> 01:41:32,320
AID WAY AFTER THANKSGIVING THIS

2667
01:41:32,320 --> 01:41:36,120
LAST YEAR HIS CONTRIBUTIONS TO

2668
01:41:36,120 --> 01:41:37,600
T-CELL BIOLOGY WILL BE KNOWN TO

2669
01:41:37,600 --> 01:41:39,680
EVERYBODY FROM MHC PRESENTATION

2670
01:41:39,680 --> 01:41:45,440
TO CO-STIMULATION, AND MODEL. 

2671
01:41:45,440 --> 01:41:47,160
HE WAS SIGNIFICANT IN MY LIFE

2672
01:41:47,160 --> 01:41:48,360
BECAUSE HE WAS MY GRADUATE

2673
01:41:48,360 --> 01:41:54,240
SCHOOL MENTOR AND I INHERITED

2674
01:41:54,240 --> 01:41:55,400
THE QUITE OBSESSION HOW TO

2675
01:41:55,400 --> 01:41:56,920
GENERATE LARGE T-CELL RESPONSE

2676
01:41:56,920 --> 01:41:57,640
AS YOU CAN.

2677
01:41:57,640 --> 01:42:01,960
AND BESIDES THAT, I CAN ONLY TO

2678
01:42:01,960 --> 01:42:05,320
HAVE INHERITED SOME DEGREE OF

2679
01:42:05,320 --> 01:42:08,760
HIS PATIENTS OVER THE YEARS.

2680
01:42:08,760 --> 01:42:10,120
HE WILL BE MISSED BUT HIS

2681
01:42:10,120 --> 01:42:12,000
THOUGHTS ARE ABSOLUTELY DEEPLY

2682
01:42:12,000 --> 01:42:12,840
EMBEDDED IN EVERYTHING I HAVE

2683
01:42:12,840 --> 01:42:20,120
BEEN THINKING ABOUT, IN MY WORK.

2684
01:42:20,120 --> 01:42:22,280
ONE THING MATT ALWAYS SAID,

2685
01:42:22,280 --> 01:42:23,800
ALWAYS TOLD ME IS IN GIVING A

2686
01:42:23,800 --> 01:42:24,560
PRESENTATION YOU FIRST TELL

2687
01:42:24,560 --> 01:42:27,280
PEOPLE WHAT YOU ARE GOING TO

2688
01:42:27,280 --> 01:42:29,680
TELL THEM, THEN YOU TELL THEM

2689
01:42:29,680 --> 01:42:30,880
WHAT YOU TOLD THEM.

2690
01:42:30,880 --> 01:42:32,680
SO IN HONOR OF HIM I WILL START

2691
01:42:32,680 --> 01:42:33,160
THAT WAY.

2692
01:42:33,160 --> 01:42:36,920
HERE ARE THE QUESTIONS I HOPE TO

2693
01:42:36,920 --> 01:42:38,600
I DRESS AND IN BLUE ARE ANSWERS,

2694
01:42:38,600 --> 01:42:40,840
WE CAN SHORT CIRCUIT THE WHOLE

2695
01:42:40,840 --> 01:42:42,600
THING, IF WE WANT TO STOP HERE

2696
01:42:42,600 --> 01:42:44,360
AND SEE IF WE HAD DEBATE BUT

2697
01:42:44,360 --> 01:42:46,000
I'LL PROCEED WITH WALKING MY WAY

2698
01:42:46,000 --> 01:42:47,680
THROUGH THIS ONE.

2699
01:42:47,680 --> 01:42:49,440
THE FIRST QUESTION I THINK IS

2700
01:42:49,440 --> 01:42:53,800
REASONABLE TO ASK, WHAT IS THE

2701
01:42:53,800 --> 01:42:55,520
WHAT NUMBER DO WE THINK WE CAN

2702
01:42:55,520 --> 01:42:59,240
GENERATE BY VACCINATION.

2703
01:42:59,240 --> 01:43:00,480
MOST AGREE (INAUDIBLE) VACCINE

2704
01:43:00,480 --> 01:43:02,400
IS REASONABLE STANDARD THAT IS

2705
01:43:02,400 --> 01:43:03,720
NOT ADJUVANTED VACCINE IT IS A

2706
01:43:03,720 --> 01:43:08,800
LIVE INFECTIOUS VACCINE BUT IT

2707
01:43:08,800 --> 01:43:09,840
REASONABLY REPRESENTS MOST

2708
01:43:09,840 --> 01:43:11,520
PEOPLE'S IDEA OF ONE OF THE BEST

2709
01:43:11,520 --> 01:43:12,960
VACCINES OUTSIDE OF SMALLPOX.

2710
01:43:12,960 --> 01:43:14,960
HERE IS DATA TRAUMA RAFI'S LAB A

2711
01:43:14,960 --> 01:43:16,400
NUMBER OF YEARS AGO WE LOOK AT

2712
01:43:16,400 --> 01:43:17,800
SINGLE EPITOPE BUT WE ARE

2713
01:43:17,800 --> 01:43:19,640
GETTING IN FREQUENCIES AS VIRUS

2714
01:43:19,640 --> 01:43:22,000
RISES AND FALLS, I DON'T KNOW IF

2715
01:43:22,000 --> 01:43:25,680
YOU CAN SEE MY POINTER HERE.

2716
01:43:25,680 --> 01:43:28,040
AS VIRUS RISES AND FALLS GETTING

2717
01:43:28,040 --> 01:43:30,000
T-CELL FREQUENCY IN 5 TO 10%

2718
01:43:30,000 --> 01:43:34,280
RANGE, THAT IS INFLUENCE BY

2719
01:43:34,280 --> 01:43:36,120
DEGREE WHICH VIRUSES IS DIVIDING

2720
01:43:36,120 --> 01:43:37,520
AND MORE VIRUS MORE VIRAL LOAD

2721
01:43:37,520 --> 01:43:40,720
YOU HAVE HIGHER T-CELL RESPONSE

2722
01:43:40,720 --> 01:43:45,880
YOU GET BUT IF YOU HAVE BACK

2723
01:43:45,880 --> 01:43:46,480
VACCINATION HOW MUCH THERE ARE

2724
01:43:46,480 --> 01:43:48,320
PER LITTER AS WELL AS HOW MUCH

2725
01:43:48,320 --> 01:43:49,800
LITTER OF BLOOD WE HAVE IN

2726
01:43:49,800 --> 01:43:52,680
FREQUENCY OF CD8 T-CELL.

2727
01:43:52,680 --> 01:43:54,840
5 TO 10% ANTIGEN T-CELL IN THE

2728
01:43:54,840 --> 01:43:57,240
BLOOD TOTALS ENTER AROUND 100 TO

2729
01:43:57,240 --> 01:43:57,840
300 MILLION CELLS.

2730
01:43:57,840 --> 01:43:59,240
THAT IS A REALLY ROBUST

2731
01:43:59,240 --> 01:43:59,880
RESPONSE.

2732
01:43:59,880 --> 01:44:01,960
AND IT IS CLEARLY UNDERESTIMATE,

2733
01:44:01,960 --> 01:44:03,320
WE ARE ONLY LOOKING AT SINGLE

2734
01:44:03,320 --> 01:44:05,520
EPITOPE AND I LEARNED ANYTHING

2735
01:44:05,520 --> 01:44:08,440
FROM ALEX SETTI, THE EPITOPE

2736
01:44:08,440 --> 01:44:09,760
DOMINANCE IN HUMANS IS VERY

2737
01:44:09,760 --> 01:44:11,560
DIFFERENT THAN MICE.  SO

2738
01:44:11,560 --> 01:44:13,320
MULTIPLE EPITOPES ACHIEVE THIS

2739
01:44:13,320 --> 01:44:16,240
BUT WE CAN PUT MAYBE AS A GOAL,

2740
01:44:16,240 --> 01:44:19,120
AS A REASONABLE GOAL FOR THE

2741
01:44:19,120 --> 01:44:23,160
SYSTEM CAN CLEARLY SUSTAIN

2742
01:44:23,160 --> 01:44:24,520
HUNDREDS OF MILLIONS OF CELLS

2743
01:44:24,520 --> 01:44:26,520
VACCINATED POST -- SO WITHIN 10

2744
01:44:26,520 --> 01:44:27,640
TO 14 DAYS AFTER VACCINATION.

2745
01:44:27,640 --> 01:44:29,640
THEN IT IS REASONABLE TO ASK HOW

2746
01:44:29,640 --> 01:44:30,680
MANY DO WE NEED TO MAKE.

2747
01:44:30,680 --> 01:44:32,720
WE CAN SPEND TIME ON THIS AND I

2748
01:44:32,720 --> 01:44:34,880
JUST WANT TO SHOOT THROUGH IT,

2749
01:44:34,880 --> 01:44:37,160
THERE IS DEBATABLE ELEMENTS BUT

2750
01:44:37,160 --> 01:44:39,000
SAM SILVERSTEIN HAD A PAPER

2751
01:44:39,000 --> 01:44:40,560
WHILE AGO WHERE HE EMPHASIZED

2752
01:44:40,560 --> 01:44:42,400
THE FACT THAT THE DEMANDS ON

2753
01:44:42,400 --> 01:44:45,000
THERAPEUTIC EFFICACY FOR T-CELL

2754
01:44:45,000 --> 01:44:46,080
GENERATION IS CONSIDERABLY

2755
01:44:46,080 --> 01:44:47,200
HIGHER THAN WHAT WE USED TO

2756
01:44:47,200 --> 01:44:48,680
THINK FOR PURPOSES OF PROTECTING

2757
01:44:48,680 --> 01:44:49,840
AGAINST ACUTE INFECTION.

2758
01:44:49,840 --> 01:44:53,000
I THINK HIS CALCULATIONS IN THIS

2759
01:44:53,000 --> 01:44:55,840
10 TO 7 T-CELLS CENTIMETERS

2760
01:44:55,840 --> 01:44:57,840
CUBED ARE REASONABLY BORN OUT

2761
01:44:57,840 --> 01:45:00,160
WITH SOME CLINICAL EVIDENCE ON

2762
01:45:00,160 --> 01:45:01,440
REQUISITION DOWN HERE AS WELL AS

2763
01:45:01,440 --> 01:45:04,800
IN CHECK POINT THERAPY, WHEN

2764
01:45:04,800 --> 01:45:06,000
SUCCESSFUL YOU CAN EVALUATE

2765
01:45:06,000 --> 01:45:09,000
TUMOR THAT'S BEEN INFILL STRAIT

2766
01:45:09,000 --> 01:45:10,040
TRAITED DEGREE IT IS

2767
01:45:10,040 --> 01:45:13,360
INFILTRATED, THE NUMBERS

2768
01:45:13,360 --> 01:45:14,080
REASONABLY FERRET THEMSELVES

2769
01:45:14,080 --> 01:45:14,520
OUT.

2770
01:45:14,520 --> 01:45:16,160
WHEREAS THERE IS DEBATE YOU CAN

2771
01:45:16,160 --> 01:45:17,600
CALCULATE WHAT THAT FREQUENCY IS

2772
01:45:17,600 --> 01:45:21,040
IN TERMS OF CELL TO BLOOD, CHAI

2773
01:45:21,040 --> 01:45:22,680
CHANGES WHEN WE LOOK AT TISSUE,

2774
01:45:22,680 --> 01:45:24,240
AS MIKE WAS BRINGING UP, THAT IS

2775
01:45:24,240 --> 01:45:29,240
A REALLY CENTRAL QUESTION THIS

2776
01:45:29,240 --> 01:45:30,720
WHOLE PROCESS OF TISSUE

2777
01:45:30,720 --> 01:45:32,520
CONCENTRATION IN CELLS THAT,

2778
01:45:32,520 --> 01:45:33,840
CEASE THE ACTIVE SITE WHERE

2779
01:45:33,840 --> 01:45:37,240
CELLS NEED TO END UP.

2780
01:45:37,240 --> 01:45:39,000
HOWEVER YOU CHOOSE TO LOOK IT IS

2781
01:45:39,000 --> 01:45:40,320
REASONABLE FOR THERAPEUTIC

2782
01:45:40,320 --> 01:45:41,560
EFFICACY IN THE TENS OF MILLIONS

2783
01:45:41,560 --> 01:45:46,520
IS WHAT WE NEED TO GET.

2784
01:45:46,520 --> 01:45:48,200
MAYBE OFF A FEW FOLD BUT NOT OFF

2785
01:45:48,200 --> 01:45:50,120
ORDER OF MAGNITUDE.

2786
01:45:50,120 --> 01:45:52,680
SO THAT TO ME IS INARGUABLY

2787
01:45:52,680 --> 01:45:53,240
HIGHER.

2788
01:45:53,240 --> 01:45:55,240
ONE WAY WE KNOW THIS IS WE HAD

2789
01:45:55,240 --> 01:45:56,840
YET TO PRODUCE THERAPEUTIC

2790
01:45:56,840 --> 01:45:58,520
VACCINE WE HAVE SEEN FREQUENCY

2791
01:45:58,520 --> 01:46:01,080
OF T-CELLS VACCINES ARE

2792
01:46:01,080 --> 01:46:01,880
GENERATING.

2793
01:46:01,880 --> 01:46:04,000
SARS COV-2 AND REASONABLE TO ASK

2794
01:46:04,000 --> 01:46:06,200
DO WE HAVE OTHER VACCINES

2795
01:46:06,200 --> 01:46:08,880
GENERATE BETTER FREQUENCIES.

2796
01:46:08,880 --> 01:46:10,000
SOME OF THE DATA YOU HAVE SEEN

2797
01:46:10,000 --> 01:46:12,520
DESCRIBED PREVIOUSLY BY SPEAKERS

2798
01:46:12,520 --> 01:46:14,440
IS LISTED HERE.

2799
01:46:14,440 --> 01:46:16,440
AND I ORIGINALLY HAD SLIDES WITH

2800
01:46:16,440 --> 01:46:18,600
ALL THE DATA WALK THROUGH BUT

2801
01:46:18,600 --> 01:46:19,480
INTERESTING THAT OBVIOUSLY

2802
01:46:19,480 --> 01:46:21,080
DOESN'T WORK WHAT IS INTERESTING

2803
01:46:21,080 --> 01:46:23,280
IS IT IS AMENABLE TO ATTAIN

2804
01:46:23,280 --> 01:46:24,200
BECAUSE EVERYBODY REASONABLY

2805
01:46:24,200 --> 01:46:28,240
COMES ONE THE SAME ANSWER.

2806
01:46:28,240 --> 01:46:31,560
WHEN YOU LOOK AT ADJUVANT E LEE

2807
01:46:31,560 --> 01:46:33,240
SITED T-CELL RESPONSES YOU GED

2808
01:46:33,240 --> 01:46:35,520
CD4 T-CELLS AUTO THE OTHER END

2809
01:46:35,520 --> 01:46:37,280
AND 1.1% OF CD8 T-CELLS.

2810
01:46:37,280 --> 01:46:37,800
AT LARGE.

2811
01:46:37,800 --> 01:46:40,040
THERE ARE OTHER PEOPLE THAT I

2812
01:46:40,040 --> 01:46:44,000
APOLOGIZE IF I LEFT OFF, I TRIED

2813
01:46:44,000 --> 01:46:46,280
TO SKEW TOWARDS SPEAKERS IN THIS

2814
01:46:46,280 --> 01:46:47,560
FOR OBVIOUS REASONS SPEAKERS IN

2815
01:46:47,560 --> 01:46:48,360
THE SESSION.

2816
01:46:48,360 --> 01:46:50,200
BUT EVERYBODY IS REASONABLY

2817
01:46:50,200 --> 01:46:54,200
GETTING THE SAME ANSWER AND SOME

2818
01:46:54,200 --> 01:46:55,440
FEEDBACK IF ANYBODY THINKS THAT

2819
01:46:55,440 --> 01:46:56,080
IS DIFFERENT.

2820
01:46:56,080 --> 01:46:57,440
THERE IS AN INTERESTING ELEMENT

2821
01:46:57,440 --> 01:47:00,360
TO MIKE'S QUESTION.

2822
01:47:00,360 --> 01:47:01,840
ABOUT FREQUENCY OF CELLS ONCE

2823
01:47:01,840 --> 01:47:05,080
YOU GETS INTO TISSUES AND AWAY

2824
01:47:05,080 --> 01:47:07,560
FROM PERIPHERAL BLOOD, BOUGH BOB

2825
01:47:07,560 --> 01:47:08,560
HAS WORK, IT IS WORTH NOTING

2826
01:47:08,560 --> 01:47:10,240
THIS IS HUMAN OR NON-HUMAN

2827
01:47:10,240 --> 01:47:14,120
PRIMATE, NONE OF THIS HERE IS

2828
01:47:14,120 --> 01:47:15,440
MOUSE.

2829
01:47:15,440 --> 01:47:17,240
IN A DIRECTION MORE APPROPRIATE.

2830
01:47:17,240 --> 01:47:19,560
BOB'S WORK LOOKING IN NON-HUMAN

2831
01:47:19,560 --> 01:47:20,720
PRY MATES HAVE SEEN IF YOU LOOK

2832
01:47:20,720 --> 01:47:23,400
IN THE LUNG THE LUNG IS REALLY

2833
01:47:23,400 --> 01:47:25,240
SENSITIVE PLACE TO FIND ANTIGEN

2834
01:47:25,240 --> 01:47:26,560
SPECIFIC T-CELLS SO WHEN YOU ASK

2835
01:47:26,560 --> 01:47:29,240
THE SUCCESS OF ADJUVANT TO

2836
01:47:29,240 --> 01:47:31,240
ELICIT T-CELL RESPONSES YOU MAY

2837
01:47:31,240 --> 01:47:32,840
STOP T-CELLS IN THE BLOOD BUT

2838
01:47:32,840 --> 01:47:34,000
TISSUE YOU FIND SIGNIFICANTLY ON

2839
01:47:34,000 --> 01:47:35,840
CAN SEN TRAITING THERE AND BEING

2840
01:47:35,840 --> 01:47:43,160
A USEFUL WAY OF GAUGING THE

2841
01:47:43,160 --> 01:47:44,040
USEFULNESS OF VACCINE.

2842
01:47:44,040 --> 01:47:45,200
THESE NUMBERS LOWER THAN TOTAL

2843
01:47:45,200 --> 01:47:47,000
IN THE BLOOD BUT THE OVER ALL

2844
01:47:47,000 --> 01:47:48,880
FOCUS CONCENTRATION COULD HAVE

2845
01:47:48,880 --> 01:47:52,320
SIGNIFICANT IMPACT AND SO

2846
01:47:52,320 --> 01:47:53,560
WHEREAS TISSUE EVALUATION OF

2847
01:47:53,560 --> 01:47:55,800
THOSE T-CELLS MAY OFFSET

2848
01:47:55,800 --> 01:47:58,000
DEFICIENCY IN GENERATING

2849
01:47:58,000 --> 01:48:00,200
ADJUVANTS T-CELLS, I WOULD SAY

2850
01:48:00,200 --> 01:48:02,760
WE ARE AT LEAST 100 FOLD OFF IN

2851
01:48:02,760 --> 01:48:04,720
HOW WELL ADJUVANTS ARE MAKING

2852
01:48:04,720 --> 01:48:07,800
T-CELL RESPONSES, TO THE GOAL WE

2853
01:48:07,800 --> 01:48:18,240
NEED THE ACHIEVE.

2854
01:48:18,240 --> 01:48:19,600
THIS IS PARTICULARLY CONFUSING

2855
01:48:19,600 --> 01:48:20,600
TO ME AND HAS BEEN FOR MANY

2856
01:48:20,600 --> 01:48:22,520
YEARS WHEN YOU TAKE A LOOK AT

2857
01:48:22,520 --> 01:48:24,640
THE DEGREE OF INNATE IMMUNITY

2858
01:48:24,640 --> 01:48:26,040
ADJUVANTS SEEM TO GENERATE.

2859
01:48:26,040 --> 01:48:29,000
T SO THIS IS SOME DATA FROM

2860
01:48:29,000 --> 01:48:31,560
BALI'S LAB TAKEN FROM ANY OF US

2861
01:48:31,560 --> 01:48:33,760
LOOKING AT APC SUB SETS AT

2862
01:48:33,760 --> 01:48:35,320
DIFFERENT ADJUVANT

2863
01:48:35,320 --> 01:48:36,520
ADMINISTRATIONS AND WHOLE HOST

2864
01:48:36,520 --> 01:48:38,240
OF ANTIGENS OF CO-STIMULATORY

2865
01:48:38,240 --> 01:48:39,760
MARKERS AND CYTOKINES AND

2866
01:48:39,760 --> 01:48:41,480
MIGRATION OF DCs AND INNATE

2867
01:48:41,480 --> 01:48:42,920
PATHWAY STIMULATED, ET CETERA.

2868
01:48:42,920 --> 01:48:44,520
ET CETERA.

2869
01:48:44,520 --> 01:48:47,080
AND GIVEN ALL THIS ROBUST INNATE

2870
01:48:47,080 --> 01:48:49,400
ACTIVATION VERY CLEARLY MONITOR

2871
01:48:49,400 --> 01:48:50,840
TERRIBLE AND MEASURABLE WITHIN

2872
01:48:50,840 --> 01:48:54,320
PRIMATES AND HUMANS IT IS

2873
01:48:54,320 --> 01:48:56,320
BAFFLING WHY GIVEN THAT

2874
01:48:56,320 --> 01:48:57,920
MAGNITUDE OF AGGREGATION WHY WE

2875
01:48:57,920 --> 01:48:59,760
HAVE REASONABLE -- I WOULD SAY

2876
01:48:59,760 --> 01:49:01,760
POOR T-CELL RESPONSES COMPARED

2877
01:49:01,760 --> 01:49:03,680
TO HOW MUCH INNATE IMMUNITY

2878
01:49:03,680 --> 01:49:06,240
SEEMS TO BE HAVE BEEN ACTIVE.

2879
01:49:06,240 --> 01:49:10,840
AND TO SOME EXTENT THAT'S

2880
01:49:10,840 --> 01:49:17,000
REINFORCED INFLAMMATION BEGETS

2881
01:49:17,000 --> 01:49:17,440
INFLAMMATION.

2882
01:49:17,440 --> 01:49:20,720
IT IS A RARE INFLAMMATION THAT

2883
01:49:20,720 --> 01:49:21,840
SUCCESSFULLY TRANSITIONS TO A

2884
01:49:21,840 --> 01:49:23,440
SUCCESSFUL ADAPTIVE IMMUNE

2885
01:49:23,440 --> 01:49:25,280
RESPONSE FOR T-CELLS PURPOSES SO

2886
01:49:25,280 --> 01:49:27,440
WE HAVE SPENT TIME CAMPING AT

2887
01:49:27,440 --> 01:49:28,200
THAT AND ASKING THE QUESTION

2888
01:49:28,200 --> 01:49:30,080
WHAT IS THE DIFFERENCE BETWEEN

2889
01:49:30,080 --> 01:49:31,960
INFLAMMATION THAT TRANSITIONS

2890
01:49:31,960 --> 01:49:33,440
EFFECTIVELY AND THE KIND THAT

2891
01:49:33,440 --> 01:49:34,520
DOESN'T AND THEY HAVE DONE SO

2892
01:49:34,520 --> 01:49:37,600
FROM PERSPECTIVE OF T-CELL

2893
01:49:37,600 --> 01:49:39,800
RESPONSE BECAUSE THOSE RULES ARE

2894
01:49:39,800 --> 01:49:43,880
DIFFERENT IF YOU ASK HOW WELL B

2895
01:49:43,880 --> 01:49:45,640
CELLS AND WELL T-CELLS, THE

2896
01:49:45,640 --> 01:49:47,920
ADJUVANT EVALUATION HAS BEEN

2897
01:49:47,920 --> 01:49:49,440
GEARED ALMOST EXCLUSIVELY I

2898
01:49:49,440 --> 01:49:50,720
WOULD SAY TOWARDS THE QUESTION

2899
01:49:50,720 --> 01:49:52,520
HOW GOOD WAS THE NEUTRALIZING

2900
01:49:52,520 --> 01:49:54,440
ANTIBODY RESPONSE OVERALL

2901
01:49:54,440 --> 01:49:55,600
ANTIBODY RESPONSE.

2902
01:49:55,600 --> 01:49:57,920
AS IT TURNS OUT ADJUVANTS THAT

2903
01:49:57,920 --> 01:49:59,680
MAKE GOOD ANTIBODY RESPONSES ARE

2904
01:49:59,680 --> 01:50:01,200
NOT NECESSARILY IN FORMULATION

2905
01:50:01,200 --> 01:50:04,640
ARE NOT NECESSARILY THE SAME

2906
01:50:04,640 --> 01:50:05,880
MADE GOOD T-CELL RESPONSE, WHAT

2907
01:50:05,880 --> 01:50:09,920
IS GOOD FOR THE GOOSE NOT GOOD

2908
01:50:09,920 --> 01:50:12,440
FOR GRANDER SO THE CATEGORY OF

2909
01:50:12,440 --> 01:50:13,600
DIFFERENCES THINKING OF BETTER

2910
01:50:13,600 --> 01:50:15,000
T-CELL RESPONSES FROM ADJUVANTS

2911
01:50:15,000 --> 01:50:17,920
THE FIRST IS STRUCTURAL.

2912
01:50:17,920 --> 01:50:19,520
IN CERTAIN TERMS FORMULATION

2913
01:50:19,520 --> 01:50:20,480
ADMINISTRATION OF VACCINE AND

2914
01:50:20,480 --> 01:50:22,520
THE SECOND IS MORE BIOLOGICAL

2915
01:50:22,520 --> 01:50:23,880
MECHANISTICALLY SPEAKING.

2916
01:50:23,880 --> 01:50:27,360
SO THE FIRST IS DIFFERENCE IN

2917
01:50:27,360 --> 01:50:32,040
FORMULATION OF ADJUVANT, IS

2918
01:50:32,040 --> 01:50:34,440
OBVIOUSLY ORIGIN OF ADJUVANT ARE

2919
01:50:34,440 --> 01:50:37,640
MORE DEEP ORIENTED OR PRETIP AT

2920
01:50:37,640 --> 01:50:40,720
A TIME ORIENT AND MAKE GOOD

2921
01:50:40,720 --> 01:50:43,480
ANTIBODY RESPONSE, SLOW LEAK

2922
01:50:43,480 --> 01:50:44,840
ANTIGEN FROM SITE IS IN CHAINS

2923
01:50:44,840 --> 01:50:46,640
DATA LOOKING AT THE MANY PUMPS

2924
01:50:46,640 --> 01:50:50,240
THAT LEAK ANTIGEN MONTH AND A

2925
01:50:50,240 --> 01:50:52,040
HALF OR SOMETHING CRAZY AND

2926
01:50:52,040 --> 01:50:54,360
ROBUSTNESS OF ANTIBODY RESPONSE,

2927
01:50:54,360 --> 01:50:56,240
IS UNBELIEVABLE THAT IS NOT A

2928
01:50:56,240 --> 01:50:58,000
GOOD THING FOR T-CELLS, THE GOOD

2929
01:50:58,000 --> 01:50:59,840
WAY TO DEMONSTRATE IS LOOKING AT

2930
01:50:59,840 --> 01:51:02,240
ADJUVANT HERE, OF COMBINED

2931
01:51:02,240 --> 01:51:05,320
ADJUVANT ADMINISTRATION, REALLY

2932
01:51:05,320 --> 01:51:07,520
ROBUST CD8 RESPONSE, REALLY HIGH

2933
01:51:07,520 --> 01:51:09,240
PERCENTAGE WITH BLOOD, BACK TO

2934
01:51:09,240 --> 01:51:10,600
MICE FOR MECHANISTIC STUDIES.

2935
01:51:10,600 --> 01:51:15,840
ALL I HAVE TO DO TO TANK THAT IS

2936
01:51:15,840 --> 01:51:16,400
-- MIMIC.

2937
01:51:16,400 --> 01:51:20,040
IF I MAKE EPIMISSION I CAN

2938
01:51:20,040 --> 01:51:21,360
DESTROY GENERATING POTENTIAL AND

2939
01:51:21,360 --> 01:51:24,120
-- DID A GOOD JOB CLARIFYING

2940
01:51:24,120 --> 01:51:29,920
EXACTLY WHAT IT IS ABOUT THAT

2941
01:51:29,920 --> 01:51:32,240
EPIMUDGES, AS WELL AS LEE RYAN

2942
01:51:32,240 --> 01:51:34,840
HARD IN TH 1 CELLS IN MARK

2943
01:51:34,840 --> 01:51:38,880
JENKINS LAB IN THAT T-CELL JOB

2944
01:51:38,880 --> 01:51:40,880
IS TO GOEN TO PERIPHERAL TISSUE

2945
01:51:40,880 --> 01:51:42,400
SEEK OUT SITES OF ANTIGEN AND

2946
01:51:42,400 --> 01:51:44,680
DESTROY AND IF YOU CREATE AN

2947
01:51:44,680 --> 01:51:48,440
ANTIGEN DEPOT USING EPIMUDGES,

2948
01:51:48,440 --> 01:51:50,040
THE ANTIBODIES ARE TURN, THE

2949
01:51:50,040 --> 01:51:51,800
T-CELLS WILL ACCESS THAT VACCINE

2950
01:51:51,800 --> 01:51:54,240
SITE, EVEN IF IT IS GIVEN TUMOR

2951
01:51:54,240 --> 01:51:56,280
YOU RATHER GO TO AND SPEND ALL

2952
01:51:56,280 --> 01:51:59,440
THEIR TIME ATTEMPTTOLOGY DESTROY

2953
01:51:59,440 --> 01:52:00,600
AND (INAUDIBLE) IF YOU STAIN

2954
01:52:00,600 --> 01:52:03,480
LEAD TO DO THAT, VACCINATION,

2955
01:52:03,480 --> 01:52:06,000
YOU CAN RECONCENTRATE CELLS AT

2956
01:52:06,000 --> 01:52:07,040
THAT INDIVIDUAL SITE.

2957
01:52:07,040 --> 01:52:10,920
SO THAT FORMULATION IS REALLY

2958
01:52:10,920 --> 01:52:13,720
DETERMINANT AND THESE ARE ALL

2959
01:52:13,720 --> 01:52:14,880
OVER SPECIFIC STUDIES SO THE

2960
01:52:14,880 --> 01:52:18,520
ANTIGEN IS THE BEST KNOWN TO

2961
01:52:18,520 --> 01:52:20,720
HUMAN KIND, I CAN DESTROY BY

2962
01:52:20,720 --> 01:52:21,920
MAKING THE DURABILITY OF THE

2963
01:52:21,920 --> 01:52:22,920
RESPONSE BY MAKING DEPOT OUT OF

2964
01:52:22,920 --> 01:52:25,280
IT.

2965
01:52:25,280 --> 01:52:28,680
SO THAT IS FORMULATION QUESTION.

2966
01:52:28,680 --> 01:52:30,400
BUT IN ADDITIONAL WAY OF GETTING

2967
01:52:30,400 --> 01:52:32,840
AT THE SAME PROBLEM, IS EVEN IF

2968
01:52:32,840 --> 01:52:35,840
I FORMULATE THE SAME IF I ADD

2969
01:52:35,840 --> 01:52:38,080
EXTRA INFLAMMATORY COMPONENTS I

2970
01:52:38,080 --> 01:52:40,000
CAN PUSH THAT SYSTEM A LITTLE

2971
01:52:40,000 --> 01:52:43,280
TOO FAR AND OUT OF REALM OF

2972
01:52:43,280 --> 01:52:45,760
DURABLE SELF-SUSTAIN T-CELL

2973
01:52:45,760 --> 01:52:46,840
RESPONSE SO IN THIS CASE TAKE

2974
01:52:46,840 --> 01:52:49,200
YOUR COMBINED AG VERDICT WHICH

2975
01:52:49,200 --> 01:52:50,840
GENERATES ROBUST MEMORY POOL,

2976
01:52:50,840 --> 01:52:53,560
AND PHENOTYPE CELLS, IF I ADD

2977
01:52:53,560 --> 01:52:57,560
CPG WHICH NUMBER OF US PLAYED IN

2978
01:52:57,560 --> 01:53:01,000
CPG AS WAY OF AUGMENTING

2979
01:53:01,000 --> 01:53:03,880
INFLAMMATORY RESPONSE FROM

2980
01:53:03,880 --> 01:53:04,440
(INAUDIBLE).

2981
01:53:04,440 --> 01:53:05,800
WHEN I DO THAT I GENERATE A

2982
01:53:05,800 --> 01:53:07,040
TREMENDOUS NUMBER OF EFFECTORS

2983
01:53:07,040 --> 01:53:08,960
WHICH SEEMS LIKE A GOOD IDEA, IT

2984
01:53:08,960 --> 01:53:10,760
IS DOUBLING THE CELLS BUT OVER

2985
01:53:10,760 --> 01:53:13,920
TIME THOSE EFFECTERS IN THAT

2986
01:53:13,920 --> 01:53:16,640
INFLAMMATORY RESPONSE IS SLOWLY

2987
01:53:16,640 --> 01:53:18,680
STEALING MY MEMORY POTENTIAL SO

2988
01:53:18,680 --> 01:53:20,000
THAT AT THE END LOWER FREQUENCY

2989
01:53:20,000 --> 01:53:21,440
OF MEMORY CELLS TO DO THE JOB

2990
01:53:21,440 --> 01:53:22,600
THAT I WOULD LIKE THEM TO STICK

2991
01:53:22,600 --> 01:53:25,240
AROUND TO DO,EN THAN IF I HAD

2992
01:53:25,240 --> 01:53:25,640
NOT DONE THAT.

2993
01:53:25,640 --> 01:53:27,600
THAT IS TRUE OF ANY ADJUVANT,

2994
01:53:27,600 --> 01:53:30,000
DUAL ADJUVANT SINGLE ADJUVANT

2995
01:53:30,000 --> 01:53:31,600
THE SAME THING, WE CAN HAVE

2996
01:53:31,600 --> 01:53:32,920
EXPANSION OF THIS INFLAMMATION

2997
01:53:32,920 --> 01:53:34,600
GENERATING MAKES A LOT OF

2998
01:53:34,600 --> 01:53:36,720
EFFECTORS BUT EVENTUALLY STEALS

2999
01:53:36,720 --> 01:53:38,400
FROM THE CAPACITY TO MAINTAIN

3000
01:53:38,400 --> 01:53:41,480
HIGH CAPACITY OF MEMORY T-CELLS

3001
01:53:41,480 --> 01:53:43,640
AT END OF THE DAY CRITICAL FOR

3002
01:53:43,640 --> 01:53:47,040
THERAPEUTIC POTENTIAL.

3003
01:53:47,040 --> 01:53:49,760
LASTLY ON THIS TOPIC BOB HAS

3004
01:53:49,760 --> 01:53:51,160
SOME OF THE BEST DATA LOOKING AT

3005
01:53:51,160 --> 01:53:52,560
IF YOU STICK WITH THE SAME

3006
01:53:52,560 --> 01:53:53,640
FORMULATION AND CHANGE THE SITE

3007
01:53:53,640 --> 01:53:56,400
OF DELIVERY, THAT CAN HAVE A

3008
01:53:56,400 --> 01:53:59,440
REALLY SIGNIFICANT IMPACT OF

3009
01:53:59,440 --> 01:54:02,000
DETERMINING IMPACT OF SUCCESS OF

3010
01:54:02,000 --> 01:54:02,760
THERAPEUTIC VACCINATION.

3011
01:54:02,760 --> 01:54:06,800
SO IN THIS CASE HE HAS A TLR 70

3012
01:54:06,800 --> 01:54:08,080
CONJUGATE INTO LIPID MICE CELL

3013
01:54:08,080 --> 01:54:10,240
AND IF YOU INJECT THAT

3014
01:54:10,240 --> 01:54:11,680
SUBCUTANEOUSLY YOU GET A TENFOLD

3015
01:54:11,680 --> 01:54:13,680
INCREASE IN FREQUENCY OF ANTIGEN

3016
01:54:13,680 --> 01:54:18,640
SPECIFIC CD8 RELATIVE TO IV

3017
01:54:18,640 --> 01:54:18,920
DELIVERY.

3018
01:54:18,920 --> 01:54:20,400
WHEN YOU LOOK AT THE PHENOTYPE

3019
01:54:20,400 --> 01:54:23,040
OF THOSE CELLS, THE IED DELIVERY

3020
01:54:23,040 --> 01:54:25,840
CREATES A MORE MEMORY PRECURSOR

3021
01:54:25,840 --> 01:54:28,440
CELLS WHEREAS SUBCUTANEOUS GIN

3022
01:54:28,440 --> 01:54:30,440
RATES AS SHOWN WITH CPG HIGH

3023
01:54:30,440 --> 01:54:32,040
NUMBER OF EFFECTORS AND THOSE --

3024
01:54:32,040 --> 01:54:34,320
THAT SEVERELY COMPROMISES THE

3025
01:54:34,320 --> 01:54:36,480
CAPACITY TO MAINTAIN

3026
01:54:36,480 --> 01:54:39,480
THERAPEUTICETH EFFICACY AGAINST

3027
01:54:39,480 --> 01:54:40,040
TUMOR.

3028
01:54:40,040 --> 01:54:43,400
SO ADDITIONALLY ONE OTHER THING

3029
01:54:43,400 --> 01:54:45,600
THAT BOB SHOWED IN COLLABORATION

3030
01:54:45,600 --> 01:54:48,240
WITH -- USING PRY MATES USING

3031
01:54:48,240 --> 01:54:49,680
THE COMBINED ADJUVANT

3032
01:54:49,680 --> 01:54:51,040
ADMINISTRATION THERE IS AN

3033
01:54:51,040 --> 01:54:54,520
ELEVATED IL 10 PRODUCTION THESE

3034
01:54:54,520 --> 01:54:56,240
ARE HIGH FREQUENCY OF RESIDENCE

3035
01:54:56,240 --> 01:54:57,280
T-CELLS, THIS ONLY HAPPENS IN

3036
01:54:57,280 --> 01:55:00,000
THE IV DELIVERY SETTING SO IV

3037
01:55:00,000 --> 01:55:02,880
DELIVERY IS OBVIOUSLY BEEN LOW

3038
01:55:02,880 --> 01:55:04,080
WHEN EVERYBODY TOTEM POLL WHEN

3039
01:55:04,080 --> 01:55:05,200
IT COMES TO VACCINE

3040
01:55:05,200 --> 01:55:05,600
ADMINISTRATION.

3041
01:55:05,600 --> 01:55:09,840
AND IT'S THOUGHT TO BE SORT OF

3042
01:55:09,840 --> 01:55:11,120
LIKE THAT'S THE THING YOU JUST

3043
01:55:11,120 --> 01:55:11,920
CAN'T GO THERE.

3044
01:55:11,920 --> 01:55:14,120
BUT WHAT IS -- AND ADMITTEDLY

3045
01:55:14,120 --> 01:55:19,880
THERE ARE CHALLENGES WITH THAT,

3046
01:55:19,880 --> 01:55:21,240
WHAT IS WORSE THAN IV

3047
01:55:21,240 --> 01:55:22,880
ADMINISTRATION OF VACCINE IS

3048
01:55:22,880 --> 01:55:24,040
HAVING NO THERAPEUTIC VACCINE

3049
01:55:24,040 --> 01:55:24,480
WHATSOEVER.

3050
01:55:24,480 --> 01:55:27,360
THAT IS A BIGGER PROBLEM SO SOME

3051
01:55:27,360 --> 01:55:30,680
OF THESE MECHANICAL AND

3052
01:55:30,680 --> 01:55:32,480
FORMULATION QUESTIONS HAVE TO

3053
01:55:32,480 --> 01:55:34,600
START GRAPPLING SPEAKING FOR

3054
01:55:34,600 --> 01:55:36,600
ALTERING THE PURPOSE OF

3055
01:55:36,600 --> 01:55:37,640
THERAPEUTIC CELL VACCINATION

3056
01:55:37,640 --> 01:55:39,640
OPPOSED TO PROTECTING AGAINST

3057
01:55:39,640 --> 01:55:40,120
ACUTE DISEASE.

3058
01:55:40,120 --> 01:55:43,280
SO LASTLY, I WANT TO TALK ABOUT

3059
01:55:43,280 --> 01:55:45,320
BIOLOGY WE THINK IS REALLY

3060
01:55:45,320 --> 01:55:46,440
CRITICALLY IMPORTANT WHEN WE

3061
01:55:46,440 --> 01:55:47,600
THINK ABOUT T-CELL GENERATING

3062
01:55:47,600 --> 01:55:48,920
VACCINES.

3063
01:55:48,920 --> 01:55:52,640
NARROWED DOWN TO JUST THE TERM

3064
01:55:52,640 --> 01:55:54,120
27s.

3065
01:55:54,120 --> 01:55:57,800
TURNS OUT IN FIT OF GOOD

3066
01:55:57,800 --> 01:55:59,920
SERENDIPITY, CD 27 AND IL 27 ARE

3067
01:55:59,920 --> 01:56:01,720
CRITICAL FOR VACCINE MANAGEMENT

3068
01:56:01,720 --> 01:56:02,600
T-CELL RESPONSE.

3069
01:56:02,600 --> 01:56:03,840
SO WE HAVE BEEN PLAYING WITH

3070
01:56:03,840 --> 01:56:05,240
THIS COMBINED ADJUVANT SOMETIME

3071
01:56:05,240 --> 01:56:08,440
AND WE KNOW THAT COMBINING

3072
01:56:08,440 --> 01:56:11,040
POLY-- TLR AGONIST WITH AGONIST

3073
01:56:11,040 --> 01:56:14,640
ANTIBODY TO CD 40 GIVES A

3074
01:56:14,640 --> 01:56:16,320
SYNERGISTIC EXPANSION CD4 AND 8

3075
01:56:16,320 --> 01:56:18,440
T-CELLS ABOVE WITH EITHER SINGLE

3076
01:56:18,440 --> 01:56:18,800
ADJUVANT.

3077
01:56:18,800 --> 01:56:21,920
AND ONE THING WE NOTICE ABOUT

3078
01:56:21,920 --> 01:56:24,040
THE DIFFERENCE BETWEEN SINGLE

3079
01:56:24,040 --> 01:56:24,800
VERSUS DUAL ADJUVANT

3080
01:56:24,800 --> 01:56:28,120
ADMINISTRATION IS IF YOU DIDN'T

3081
01:56:28,120 --> 01:56:29,440
ADMINISTER BOTH ADJUVANTS

3082
01:56:29,440 --> 01:56:31,720
TOGETHER, YOU WOULDN'T GET ANY

3083
01:56:31,720 --> 01:56:33,720
UPREGULATION OF CD 7 WHICH IS

3084
01:56:33,720 --> 01:56:35,640
LIGAND FOR CD 27 AND GENERALLY

3085
01:56:35,640 --> 01:56:37,840
TRUE OF OTHER GENE RECEPTOR

3086
01:56:37,840 --> 01:56:39,840
LIGANDS, THEY NEEDED MULTIPLE

3087
01:56:39,840 --> 01:56:41,320
HITS IN ORDER TO BE UPREGULATED.

3088
01:56:41,320 --> 01:56:43,640
THIS IS DIFFERENT THAN IN VITRO,

3089
01:56:43,640 --> 01:56:45,640
THIS IS ALL DONE IN VIVO.

3090
01:56:45,640 --> 01:56:47,400
WE HAVE SEEN IT IN PRIMATES AS

3091
01:56:47,400 --> 01:56:48,320
WELL.

3092
01:56:48,320 --> 01:56:50,040
IN VITRO STICK IN A DISH YOU GET

3093
01:56:50,040 --> 01:56:51,120
CD 7 TO DO WHATEVER YOU WANT.

3094
01:56:51,120 --> 01:56:53,360
SO IN VIVO REGULATION OF THIS

3095
01:56:53,360 --> 01:56:55,600
PARTICULAR MARKER THIS TNF

3096
01:56:55,600 --> 01:56:57,080
LIGAND FAMILY MEMBER IS

3097
01:56:57,080 --> 01:56:58,640
DEPENDENT ON MULTIPLE

3098
01:56:58,640 --> 01:57:02,040
INFLAMMATORY SIGNAL AND THE

3099
01:57:02,040 --> 01:57:03,560
T-CELL RESPONSE DOWNSTREAM CD8

3100
01:57:03,560 --> 01:57:05,240
T-CELLS RESPONSE IS REALLY

3101
01:57:05,240 --> 01:57:06,840
HAMSTRUNG SOON AS YOU BLOCK THAT

3102
01:57:06,840 --> 01:57:08,920
PARTICULAR INTERACTION BETWEEN

3103
01:57:08,920 --> 01:57:10,640
CD 7 AND CD 27.

3104
01:57:10,640 --> 01:57:14,000
CD4 CELLS ARE MORE DETEN DENT ON

3105
01:57:14,000 --> 01:57:16,880
OX 40 AND ANTI-CD 70 AS WELL AS

3106
01:57:16,880 --> 01:57:19,480
CD 27 BUT CD8 ARE VERY FOCUSED

3107
01:57:19,480 --> 01:57:36,640
ON CD 27.

3108
01:57:36,640 --> 01:57:39,400
VACCINE RESPONSE IS OVEREPIFA US

3109
01:57:39,400 --> 01:57:39,600
SHOD.

3110
01:57:39,600 --> 01:57:41,400
THIS IS NOT JUST US SAYING THIS

3111
01:57:41,400 --> 01:57:43,040
BUT HEAVY HITTERS ACROSS THE

3112
01:57:43,040 --> 01:57:45,080
BOARD ACKNOWLEDGING THE CENTRAL

3113
01:57:45,080 --> 01:57:48,320
NATURE OF CD 27, CD 7

3114
01:57:48,320 --> 01:57:49,840
DETERMINING THE OUTCOME OF

3115
01:57:49,840 --> 01:57:58,680
SUCCESSFUL T-CELL RESPONSES.

3116
01:57:58,680 --> 01:58:00,680
AND IL 7 IS SOMETHING WE HAVE

3117
01:58:00,680 --> 01:58:02,040
BEEN LOOK AT.

3118
01:58:02,040 --> 01:58:03,080
IL 27 AS FAR AS WE CAN TELL THE

3119
01:58:03,080 --> 01:58:05,360
ONLY INNATE FACTOR THAT

3120
01:58:05,360 --> 01:58:09,440
SUCCESSFULLY PREDICTS T-CELL

3121
01:58:09,440 --> 01:58:09,840
ADAPTED OUTPUT.

3122
01:58:09,840 --> 01:58:11,200
WE MADE A REPORTER MOUSE WHERE

3123
01:58:11,200 --> 01:58:13,600
WE CAN SEE THAT AFTER ADJUVANT

3124
01:58:13,600 --> 01:58:15,920
ADMINISTRATION CDC 1 PREDOMINANT

3125
01:58:15,920 --> 01:58:18,960
DC SUBTYPE THAT MAKES IL 27

3126
01:58:18,960 --> 01:58:21,000
AFTER ADJUVANT ADMINISTRATION.

3127
01:58:21,000 --> 01:58:25,080
YOU CAN STRATIFY THE AMOUNT OF

3128
01:58:25,080 --> 01:58:26,800
GFP MADE BASED AFTER DIFFERENT

3129
01:58:26,800 --> 01:58:27,240
ADJUVANTS.

3130
01:58:27,240 --> 01:58:28,960
AND WHEN YOU DO THAT, WHAT YOU

3131
01:58:28,960 --> 01:58:30,480
END UP SIGHING IS THAT THE

3132
01:58:30,480 --> 01:58:32,960
AMOUNT OF GFP MADE WITHIN SIX

3133
01:58:32,960 --> 01:58:34,440
HOURS OF ADJUVANT ADMINISTRATION

3134
01:58:34,440 --> 01:58:36,280
IS PREDICTIVE AND CORRELATIVE OF

3135
01:58:36,280 --> 01:58:38,600
THE T-CELL RESPONSE 80 DAYS

3136
01:58:38,600 --> 01:58:39,080
LATER.

3137
01:58:39,080 --> 01:58:41,600
10 AS WELL AS 80 DAYS LATER.

3138
01:58:41,600 --> 01:58:43,120
THIS IS NOT TRUE, IMPORTANTLY OF

3139
01:58:43,120 --> 01:58:44,120
CYTOKINES THAT EVERYBODY THINKS

3140
01:58:44,120 --> 01:58:46,120
SHOULD BE MORE PREDICTIVE OF

3141
01:58:46,120 --> 01:58:49,560
T-CELL RESPONSES DOWNSTREAM LIKE

3142
01:58:49,560 --> 01:58:50,200
IL 12.

3143
01:58:50,200 --> 01:58:51,840
SIX HOURS AFTER ADJUVANTS I CAN

3144
01:58:51,840 --> 01:58:53,280
SAY WITH GOOD ACCURACY

3145
01:58:53,280 --> 01:58:56,440
REMARKABLE ACCURACY, WHAT TO

3146
01:58:56,440 --> 01:58:59,120
EXPECT T-CELLS RESPONSE

3147
01:58:59,120 --> 01:58:59,480
DOWNSTREAM.

3148
01:58:59,480 --> 01:59:01,560
WE LOOK AT THIS FOR PREDICTIVE

3149
01:59:01,560 --> 01:59:02,840
PURPOSES BECAUSE WE FOUND FROM

3150
01:59:02,840 --> 01:59:05,960
KNOCK OUTS IF WE TRY TO IMMUNIZE

3151
01:59:05,960 --> 01:59:08,040
ALPHA ONE RECEPTOR KNOCK OUT WE

3152
01:59:08,040 --> 01:59:09,280
GET ANTIBODY RESPONSES THAT ARE

3153
01:59:09,280 --> 01:59:12,040
T-CELL RESPONSES CD4 AND 8 ARE

3154
01:59:12,040 --> 01:59:12,560
SUPER (INAUDIBLE).

3155
01:59:12,560 --> 01:59:14,760
THAT'S NOT TRUE OF INFECTION

3156
01:59:14,760 --> 01:59:15,600
WHERE IN THIS CASE IT IS

3157
01:59:15,600 --> 01:59:18,000
SLIGHTLY ELEVATED VACCINE BUT

3158
01:59:18,000 --> 01:59:21,120
OTHER INFECTIONS DRAMATICALLY

3159
01:59:21,120 --> 01:59:23,720
ELEVATED WHERE IL 27 JOB IS

3160
01:59:23,720 --> 01:59:25,200
BRING THINGS WITH THE END

3161
01:59:25,200 --> 01:59:26,440
OPPOSED TO RAMPING UP AT THE

3162
01:59:26,440 --> 01:59:26,880
BEING.

3163
01:59:26,880 --> 01:59:28,640
HERE IS QUANTIFICATION OF THAT,

3164
01:59:28,640 --> 01:59:30,360
COMPARED TO ADVANTAGE SINIA.

3165
01:59:30,360 --> 01:59:31,520
THIS IS -- VAX SINIA.

3166
01:59:31,520 --> 01:59:33,960
THIS IS NOT A DUAL VACCINE

3167
01:59:33,960 --> 01:59:36,000
ADJUVANT PROBLEM THIS IS ALL

3168
01:59:36,000 --> 01:59:38,280
ADJUVANTS SEEM TO BE HEAVILY IL

3169
01:59:38,280 --> 01:59:40,880
27, MORE RECENTLY DONE mRNA

3170
01:59:40,880 --> 01:59:43,240
VACCINE THAT ARE CLEARLY IL 27

3171
01:59:43,240 --> 01:59:44,800
FOR PURPOSES OF GENERATING

3172
01:59:44,800 --> 01:59:50,920
T-CELL RESPONSES.  SO LET ME

3173
01:59:50,920 --> 01:59:51,840
THINK STRUCTURALLY HOW TO

3174
01:59:51,840 --> 01:59:53,240
DELIVER VACCINES IN FORMULATING

3175
01:59:53,240 --> 01:59:57,840
THEM AS WELL AS THE 27s, AS

3176
01:59:57,840 --> 02:00:00,040
BIOLOGICAL MECHANISM ARE REALLY

3177
02:00:00,040 --> 02:00:01,800
IMPORTANT SUCH THAT WE SHOULD BE

3178
02:00:01,800 --> 02:00:03,600
THINKING HARD AS WE ARE

3179
02:00:03,600 --> 02:00:05,640
SCREENING NEW ADJUVANTS WE

3180
02:00:05,640 --> 02:00:06,920
ADVOCATE TO THINK MORE ABOUT

3181
02:00:06,920 --> 02:00:08,920
WHAT INDUCES CD 78 EXPRESSION

3182
02:00:08,920 --> 02:00:11,440
AND WHAT INDUCES IL 27.

3183
02:00:11,440 --> 02:00:15,920
AS WE ARE LOOKING FOR THAT.

3184
02:00:15,920 --> 02:00:17,480
WHAT IS MY -- I FORGOT TO START

3185
02:00:17,480 --> 02:00:21,760
MY TIME, WHAT IS -- JULIE

3186
02:00:21,760 --> 02:00:22,640
KEEPING TRACK?

3187
02:00:22,640 --> 02:00:23,880
>> YOU SHOULD TRY TO WRAP UP.

3188
02:00:23,880 --> 02:00:27,120
>> GOT YOU.

3189
02:00:27,120 --> 02:00:28,040
YEP GOOD.

3190
02:00:28,040 --> 02:00:30,040
I'LL JUST MENTION LASTLY, I

3191
02:00:30,040 --> 02:00:32,080
FIGURED I WOULDN'T GET THROUGH

3192
02:00:32,080 --> 02:00:32,520
THIS.

3193
02:00:32,520 --> 02:00:34,040
BUT GO -- SKIP TO THE END, WHAT

3194
02:00:34,040 --> 02:00:39,200
WE THINK IL 27 IS DOING, -- WHAT

3195
02:00:39,200 --> 02:00:42,960
WE THINK IL 27 IS DOING CD 27

3196
02:00:42,960 --> 02:00:45,160
AND IL 27 PROBLEM IN VACCINE

3197
02:00:45,160 --> 02:00:46,560
ELICITED RESPONSE IS GETTING

3198
02:00:46,560 --> 02:00:48,600
MOSTLY MEMORY CELLS, FADED MOST

3199
02:00:48,600 --> 02:00:49,840
MEMORY INFECTIOUS SETTING IS

3200
02:00:49,840 --> 02:00:52,760
FADED TO BAIL OUT OF CLONAL

3201
02:00:52,760 --> 02:00:53,960
EXPANSION AND BIOMASS

3202
02:00:53,960 --> 02:00:56,640
ACQUISITION AND GO MORE

3203
02:00:56,640 --> 02:00:58,280
QUIESCENT, WHEREAS EFFECTER

3204
02:00:58,280 --> 02:01:01,760
CELLS ARE DRIVEN TOWARDS BIOMASS

3205
02:01:01,760 --> 02:01:02,800
CLONAL EXPANSION.

3206
02:01:02,800 --> 02:01:04,120
IN A VACCINE SETTING WE ARE

3207
02:01:04,120 --> 02:01:06,720
DRIVING MEMORY PHENOTYPE SO ITS

3208
02:01:06,720 --> 02:01:09,240
FATE IS DISCONNECTED FROM

3209
02:01:09,240 --> 02:01:10,720
BIOMASS DEMANDS.

3210
02:01:10,720 --> 02:01:13,600
BUT IL 27 AND CD 27 ARE

3211
02:01:13,600 --> 02:01:14,880
SIGNIFICANTLY CONTRIBUTING TO

3212
02:01:14,880 --> 02:01:16,920
MAINTAINING CMIC FUNCTION AFTER

3213
02:01:16,920 --> 02:01:18,240
TRANSCRIPTION DECLINES AN

3214
02:01:18,240 --> 02:01:19,760
FACILITATING CLONAL EXPANSION

3215
02:01:19,760 --> 02:01:23,440
WITHIN SPECIFICALLY MEMORY

3216
02:01:23,440 --> 02:01:25,360
PHENOTYPE CELL AND WE CAN GAUGE

3217
02:01:25,360 --> 02:01:25,760
THAT.

3218
02:01:25,760 --> 02:01:27,840
SO WE THINK THAT IS THE

3219
02:01:27,840 --> 02:01:30,040
BIOLOGICAL MECHANISM OF 27s

3220
02:01:30,040 --> 02:01:31,760
AND WE ARE IN THE PROCESS OF

3221
02:01:31,760 --> 02:01:34,720
SINGLE CELL DATA AND

3222
02:01:34,720 --> 02:01:35,800
TRANSCRIPTIONAL DATA BEHIND THAT

3223
02:01:35,800 --> 02:01:37,080
AS WELL AS FUNCTIONAL DATA.

3224
02:01:37,080 --> 02:01:39,560
SO THAT IS WHERE WE THINK THAT

3225
02:01:39,560 --> 02:01:40,040
IS GOING.

3226
02:01:40,040 --> 02:01:43,360
AGAIN THINKING HARD SCREENING

3227
02:01:43,360 --> 02:01:45,200
FOR AGONISTENINGS ADJUVANTS THAT

3228
02:01:45,200 --> 02:01:46,560
DRIVE THOSE PARTICULAR PATHWAYS

3229
02:01:46,560 --> 02:01:50,840
IS AN IMPORTANT FEATURE.

3230
02:01:50,840 --> 02:01:54,720
SO IN OUR MAP, THANKS TO ALL

3231
02:01:54,720 --> 02:01:56,080
THOSE THAT WERE IN THE LAB DOING

3232
02:01:56,080 --> 02:01:59,800
THE WORK, PRIMARILY DARIA SCOTT

3233
02:01:59,800 --> 02:02:03,680
AND JARROD AS WELL AS

3234
02:02:03,680 --> 02:02:06,440
COLLABORATION WITH (INAUDIBLE).

3235
02:02:06,440 --> 02:02:07,360
>> THANKS, ROSS.

3236
02:02:07,360 --> 02:02:10,200
QUESTIONS FOR ROSS?

3237
02:02:10,200 --> 02:02:13,720
PLEASE RAISE YOUR HAND.

3238
02:02:13,720 --> 02:02:16,080
>> I'LL STOP.

3239
02:02:16,080 --> 02:02:19,000
>> ROSS LET ME ASK YOU A

3240
02:02:19,000 --> 02:02:19,400
QUESTION.

3241
02:02:19,400 --> 02:02:24,000
SO THIS CONCEPT OF EXPANDING

3242
02:02:24,000 --> 02:02:25,960
MORE THAN WE LIKE LESS

3243
02:02:25,960 --> 02:02:29,040
DIFFERENTIATED CELL, VACCINATION

3244
02:02:29,040 --> 02:02:32,400
OF INTEREST BUT HAVE YOU LOOKED

3245
02:02:32,400 --> 02:02:33,840
AT EPIGENETICS OF THESE?

3246
02:02:33,840 --> 02:02:38,520
ONE OF THE THINGS THAT HAPPENS

3247
02:02:38,520 --> 02:02:41,880
WHEN CELLS GO TO INFECTED PHASE

3248
02:02:41,880 --> 02:02:44,040
AMEND DEVELOP CELLS THERE ARE

3249
02:02:44,040 --> 02:02:48,640
STRIKING EPIGENETIC CHANGES, CD8

3250
02:02:48,640 --> 02:02:51,360
PERFORIN LOCUST REMAINS

3251
02:02:51,360 --> 02:02:52,760
(INAUDIBLE) THE GRANZYME REMAINS

3252
02:02:52,760 --> 02:02:54,240
(INAUDIBLE).

3253
02:02:54,240 --> 02:02:58,560
THIS ALLOWS INTERFERON GAMMA --

3254
02:02:58,560 --> 02:03:00,440
THIS ALLOWS CELLS TO RESPOND

3255
02:03:00,440 --> 02:03:03,120
MUCH FASTER IN TERMS OF

3256
02:03:03,120 --> 02:03:06,480
EXPRESSING -- SO HAVE YOU LOOKED

3257
02:03:06,480 --> 02:03:10,360
AT EFFECTOR GENES TO DELIVER

3258
02:03:10,360 --> 02:03:10,880
NAIVE CELLS?

3259
02:03:10,880 --> 02:03:13,040
>> SO WE HAVEN'T SEEN -- LOOKED

3260
02:03:13,040 --> 02:03:15,000
AT METHYLATION STATUS BUT WE

3261
02:03:15,000 --> 02:03:16,600
HAVE DONE ATTACK SEQ AS WELL AS

3262
02:03:16,600 --> 02:03:17,440
SINGLE CELL SEQ.

3263
02:03:17,440 --> 02:03:19,640
THE THING CURE OUTABOUT ADJUVANT

3264
02:03:19,640 --> 02:03:20,640
ELICITED CELLS IS THEY GO

3265
02:03:20,640 --> 02:03:23,000
THROUGH A PATHWAY, A

3266
02:03:23,000 --> 02:03:24,080
TRANSCRIPTIONAL PATHWAY THAT IS

3267
02:03:24,080 --> 02:03:26,640
NOT -- DOESN'T SEEM TO BE

3268
02:03:26,640 --> 02:03:27,720
EXPERIENCED BY INFECTION OF

3269
02:03:27,720 --> 02:03:29,640
THOSE T-CELLS SO INFECTION

3270
02:03:29,640 --> 02:03:31,400
ELICITED CELLS SOLVED THIS

3271
02:03:31,400 --> 02:03:33,560
PROBLEM OF EXPANDS O AND WHO

3272
02:03:33,560 --> 02:03:35,560
DOESN'T AND SELF-REMULE FOR

3273
02:03:35,560 --> 02:03:36,520
MEMORY AND THOUSAND GET RID OF

3274
02:03:36,520 --> 02:03:38,160
THIS THING IN FRONT OF US BY

3275
02:03:38,160 --> 02:03:39,200
GAUGING THE AMOUNT OF

3276
02:03:39,200 --> 02:03:41,080
INFLAMMATION THAT IS AROUND AND

3277
02:03:41,080 --> 02:03:42,360
DRAMATICALLY EFFECTING THIS

3278
02:03:42,360 --> 02:03:44,400
SUSTAINED CMIC FUNCTION

3279
02:03:44,400 --> 02:03:45,040
TRANSCRIPTION.

3280
02:03:45,040 --> 02:03:46,600
WHEREAS THE MEMORY CELLS BAIL

3281
02:03:46,600 --> 02:03:48,160
OUT OF THAT QUESTION ENTIRELY

3282
02:03:48,160 --> 02:03:50,200
AND ARE THERE FOR SELF-RENEWING

3283
02:03:50,200 --> 02:03:50,640
PURPOSES.

3284
02:03:50,640 --> 02:03:52,000
ADJUVANT SETTING IT IS -- WE ARE

3285
02:03:52,000 --> 02:03:53,560
PUSHING ALL THE PATHWAYS AT ONCE

3286
02:03:53,560 --> 02:03:56,240
SO UNLIKE INFECTION WHERE IF YOU

3287
02:03:56,240 --> 02:03:59,160
HAVE HIGH IBIT YOU HAVE LOW TCF

3288
02:03:59,160 --> 02:04:01,560
1 AND IN AN ADJUVANT ELICITED

3289
02:04:01,560 --> 02:04:03,240
CELL YOU HAVE HIGH -- EXTREMELY

3290
02:04:03,240 --> 02:04:08,040
HIGH TCF 1 AND HIGH CMIC SO THIS

3291
02:04:08,040 --> 02:04:10,160
ODD CELL TYPE IS TRYING TO DO

3292
02:04:10,160 --> 02:04:11,560
ALL THAT AT THE SAME TIME AND WE

3293
02:04:11,560 --> 02:04:12,680
HAVE SEEN A TRAININGS

3294
02:04:12,680 --> 02:04:14,960
SUBSCRIPTIONAL UNIQUENESS TO

3295
02:04:14,960 --> 02:04:16,440
WHAT WE SEE REFERRED TO AS T

3296
02:04:16,440 --> 02:04:18,000
BAGS COMPARED TO THE PATH WHICH

3297
02:04:18,000 --> 02:04:19,760
INFECTION CREATES THESE TWO SUB

3298
02:04:19,760 --> 02:04:21,160
SETS AND THEN ONE KEEPS GOING

3299
02:04:21,160 --> 02:04:24,640
AND THE OTHER ONE DIES OFF.

3300
02:04:24,640 --> 02:04:26,880
SO THE METHYLATION STATUS IS

3301
02:04:26,880 --> 02:04:28,560
GOOD, WE HAVEN'T GOT TO IT YET

3302
02:04:28,560 --> 02:04:30,800
BUT WE HAVE TRANSCRIPTIONAL DATA

3303
02:04:30,800 --> 02:04:34,160
AND THERE'S A VERY GOOD WAY C

3304
02:04:34,160 --> 02:04:38,040
CELLS EVOLVE.

3305
02:04:38,040 --> 02:04:39,960
>> 

3306
02:04:39,960 --> 02:04:40,520
>> THAT WAS BEAUTIFUL.

3307
02:04:40,520 --> 02:04:44,000
IF I REMEMBER CORRECTLY SRI

3308
02:04:44,000 --> 02:04:47,120
YEAH'S LAB HAD DONE WORK ON R 27

3309
02:04:47,120 --> 02:04:49,640
AND HE PUBLISHED ON IL 27

3310
02:04:49,640 --> 02:04:51,880
PROMOTING REGULATORY LIKE TR 1

3311
02:04:51,880 --> 02:04:53,760
TYPE CELL AND SO THIS IS IS

3312
02:04:53,760 --> 02:04:56,120
SOMEWHAT AT ODDS WITH

3313
02:04:56,120 --> 02:04:58,360
FUNCTIONING AND WE AGREE IT

3314
02:04:58,360 --> 02:05:01,440
PROMOTES TH 1 TYPE RESPONSES.

3315
02:05:01,440 --> 02:05:02,440
WOULD YOU COMMENTS OWN THAT

3316
02:05:02,440 --> 02:05:04,560
>> I WOULD LIKE TO FULLY A AGREE

3317
02:05:04,560 --> 02:05:05,880
WITH YOU IT DOES DO THAT BUT

3318
02:05:05,880 --> 02:05:07,160
IT'S CONTEXT APPROPRIATE SO

3319
02:05:07,160 --> 02:05:08,840
AFTER ADJUVANT ADMINISTRATION,

3320
02:05:08,840 --> 02:05:11,040
VERY RA SPIKE AND DROP OF THAT

3321
02:05:11,040 --> 02:05:14,440
AND T-CELLS ARE BANKING ON THAT.

3322
02:05:14,440 --> 02:05:18,040
FOR THE INITIALING RAMPING UP OR

3323
02:05:18,040 --> 02:05:20,040
T-CELL RESPONSE AND SURVIVAL

3324
02:05:20,040 --> 02:05:22,080
DROPS OFF SURVIVE AND BIOMASS

3325
02:05:22,080 --> 02:05:24,640
ACQUISITION AT CMIIC
EVAPORATION.

3326
02:05:24,640 --> 02:05:27,640
IN A CANCER CHRONIC SETTING L 27

3327
02:05:27,640 --> 02:05:29,680
ABSOLUTELY THE JOB IS TO REIGN

3328
02:05:29,680 --> 02:05:31,680
THINGS IN SO IL 27 IS REIGNING

3329
02:05:31,680 --> 02:05:34,440
IN TUMOR SETTING OR CHRONIC

3330
02:05:34,440 --> 02:05:35,520
INFECTIOUS SETTING THE SAME WAY,

3331
02:05:35,520 --> 02:05:37,320
IF YOU GET RID OF IT ACUTE

3332
02:05:37,320 --> 02:05:39,240
SETTING OFTEN T-CELLS EXPAND SO

3333
02:05:39,240 --> 02:05:41,200
MUCH IT KILLS THE HOST SO MOST

3334
02:05:41,200 --> 02:05:43,440
THAT WAS THE SURPRISE OF ITS

3335
02:05:43,440 --> 02:05:45,440
CRITICAL FUNCTION AND ADJUVANT

3336
02:05:45,440 --> 02:05:46,520
ELICITED RESPONSE TO EVERYBODY

3337
02:05:46,520 --> 02:05:48,560
ELSE, NO, NO, THIS IS A

3338
02:05:48,560 --> 02:05:50,160
SUPPRESSIVE SETTING, ACTUALLY IN

3339
02:05:50,160 --> 02:05:51,640
THIS CONTEXT CRITICAL FRONT END

3340
02:05:51,640 --> 02:05:54,320
TO MAKE SURE EVERYONE RAMPS UP

3341
02:05:54,320 --> 02:05:54,880
PROPERLY.

3342
02:05:54,880 --> 02:05:58,280
>> THANK YOU.

3343
02:05:58,280 --> 02:06:02,560
LET'S MOVE TO THE NEXT SPEAKER,

3344
02:06:02,560 --> 02:06:03,960
DONNA FARBER, DONNA WILL TELL US

3345
02:06:03,960 --> 02:06:07,120
ABOUT TISSUE IMMUNITY.

3346
02:06:07,120 --> 02:06:09,800
>> THANK YOU.

3347
02:06:09,800 --> 02:06:12,840
I'M OUT OF TOWN AT AND IN PERSON

3348
02:06:12,840 --> 02:06:13,480
MEETING A VAIR RARE EVENT BUT

3349
02:06:13,480 --> 02:06:14,840
WHAT HAPPENED IS THE HOTEL

3350
02:06:14,840 --> 02:06:17,640
INTERNET IS PROFOUNDLY UNSTABLE

3351
02:06:17,640 --> 02:06:19,720
SO THAT IS WHY I HAVE TO KEEP MY

3352
02:06:19,720 --> 02:06:22,360
VIDEO OFF, THEY ARE SHARING THE

3353
02:06:22,360 --> 02:06:24,760
SCREEN FROM NIH.

3354
02:06:24,760 --> 02:06:26,040
SO THERE MIGHT BE A LITTLE BIT

3355
02:06:26,040 --> 02:06:26,520
DELAY.

3356
02:06:26,520 --> 02:06:27,520
>> WE CAN SEE YOUR SLIDES.

3357
02:06:27,520 --> 02:06:28,640
>> OKAY.

3358
02:06:28,640 --> 02:06:30,600
CAN YOU TAKE IT BACK TO THE

3359
02:06:30,600 --> 02:06:31,200
BEGINNING?

3360
02:06:31,200 --> 02:06:37,800
THAT IS NOT THE FIRST SLIDE.

3361
02:06:37,800 --> 02:06:38,640
>> I CAN DO THAT.

3362
02:06:38,640 --> 02:06:39,960
CAN YOU CONTROL IT?

3363
02:06:39,960 --> 02:06:43,560
>> I CAN CONTROL IT.

3364
02:06:43,560 --> 02:06:44,000
THANK YOU VERY MUCH.

3365
02:06:44,000 --> 02:06:46,240
SO THERE IS A LITTLE BIT OF A

3366
02:06:46,240 --> 02:06:48,800
LAG, SO PLEASE BEAR WITH ME,

3367
02:06:48,800 --> 02:06:54,000
HOPE H THIS WILL GO FORWARD.

3368
02:06:54,000 --> 02:06:56,760
SO I'M GOING TO BE TALKING TO

3369
02:06:56,760 --> 02:06:57,960
YOU ABOUT MEMORY.

3370
02:06:57,960 --> 02:06:59,320
CAN EVERYBODY SEE THE NEXT

3371
02:06:59,320 --> 02:06:59,960
SLIDE?

3372
02:06:59,960 --> 02:07:05,800
I'M NOT SEEING (OVERLAPPING

3373
02:07:05,800 --> 02:07:09,880
SPEAKERS)

3374
02:07:09,880 --> 02:07:12,920
>> ON YOUR FIRST SLIDE.

3375
02:07:12,920 --> 02:07:15,880
>> CAN YOU SET IT TO THE NEXT

3376
02:07:15,880 --> 02:07:16,280
SLIDE PLEASE.

3377
02:07:16,280 --> 02:07:16,760
THANK YOU.

3378
02:07:16,760 --> 02:07:18,240
>> CAN YOU MAYBE CONTROL THIS?

3379
02:07:18,240 --> 02:07:19,840
>> YEAH, JUST GIVE ME THE QUEUE

3380
02:07:19,840 --> 02:07:21,000
FOR THE NEXT SLIDE.

3381
02:07:21,000 --> 02:07:21,560
>> OKAY.

3382
02:07:21,560 --> 02:07:23,400
THANK YOU.

3383
02:07:23,400 --> 02:07:26,280
>> WE HEARD ABOUT MEMORY AND

3384
02:07:26,280 --> 02:07:28,360
WHAT I WILL BE ADDING TO THIS

3385
02:07:28,360 --> 02:07:30,280
WILL BE ABOUT DIFFERENT KINDS OF

3386
02:07:30,280 --> 02:07:31,880
MEMORY SUB SETS, IN PARTICULAR

3387
02:07:31,880 --> 02:07:34,640
THE ONES THAT ARE IN TISSUE.

3388
02:07:34,640 --> 02:07:36,040
SO THERE'S SEVERAL DIFFERENT

3389
02:07:36,040 --> 02:07:37,920
TYPES OF CIRCULATING MEMORY SUB

3390
02:07:37,920 --> 02:07:41,000
SETS, CENTRAL MEMORY THAT WILL

3391
02:07:41,000 --> 02:07:43,040
GO TO THE LYMPHOID TISSUE AND

3392
02:07:43,040 --> 02:07:45,240
EFFECTOR MEMORY THAT CAN MIGRATE

3393
02:07:45,240 --> 02:07:47,120
THROUGH OTHER SITES AS WELL AS

3394
02:07:47,120 --> 02:07:49,120
THAT CIRCULATING TUMORAL

3395
02:07:49,120 --> 02:07:50,920
EFFECTOR BUT THE MAJORITY OF

3396
02:07:50,920 --> 02:07:52,440
MEMORY CELLS AND TISSUES ARE

3397
02:07:52,440 --> 02:07:53,280
TISSUE RESONANT.

3398
02:07:53,280 --> 02:07:54,600
THEY ARE NON-CIRCULATING.

3399
02:07:54,600 --> 02:07:56,800
THEY HAVE UNIQUE PHENOTYPE THAT

3400
02:07:56,800 --> 02:07:58,840
DISTINGUISH FROM CIRCULATING,

3401
02:07:58,840 --> 02:08:02,000
EXPRESSING EXISTING EYE AND CD

3402
02:08:02,000 --> 02:08:04,840
103 AND DISTINCT PROFILE FOUND

3403
02:08:04,840 --> 02:08:06,000
IN MULTIPLE PERIPHERAL SITES.

3404
02:08:06,000 --> 02:08:09,880
NEXT SLIDE.

3405
02:08:09,880 --> 02:08:11,440
HAD IS IMPORTANT ABOUT TISSUE

3406
02:08:11,440 --> 02:08:15,600
RESIDENT MEMORY CELLS IS TO

3407
02:08:15,600 --> 02:08:17,800
INFECTION PARTICULARLY SITE

3408
02:08:17,800 --> 02:08:20,080
SPECIFIC INFECTION MEDIATE THAT

3409
02:08:20,080 --> 02:08:20,800
OPTIMUM IMMUNITY.

3410
02:08:20,800 --> 02:08:22,480
THIS IS SHOWN IN MULTIPLE

3411
02:08:22,480 --> 02:08:23,880
TISSUES AN MULTIPLE SITES AND

3412
02:08:23,880 --> 02:08:28,640
OUR CONTRIBUTION IN THE LUNG IS

3413
02:08:28,640 --> 02:08:30,080
WE FOUND IN FLUORESCENT STAIN OF

3414
02:08:30,080 --> 02:08:32,720
THE LUNG THE MOUSE LUNG A ALVEO

3415
02:08:32,720 --> 02:08:34,800
LIE AND TISSUE RESIDENT MEMORY

3416
02:08:34,800 --> 02:08:35,840
LOCALIZE AROUND AIRWAY SO THEY

3417
02:08:35,840 --> 02:08:37,040
ARE MAINTAINED AT SITE OF

3418
02:08:37,040 --> 02:08:37,440
INFECTION.

3419
02:08:37,440 --> 02:08:42,560
AND THE LOWER GRAPH IN THE LEFT

3420
02:08:42,560 --> 02:08:43,640
MOUSE MODEL WE USE TRANSFER

3421
02:08:43,640 --> 02:08:46,640
MODEL IN A MOUSE WITH ONLY LUNG

3422
02:08:46,640 --> 02:08:48,840
RESIDENT MEMORY THERE'S OOH FULL

3423
02:08:48,840 --> 02:08:50,240
CHALLENGE WHEREAS MICE WITH

3424
02:08:50,240 --> 02:08:52,280
SPLEEN DERIVED MEMORY YOU CAN GO

3425
02:08:52,280 --> 02:08:54,920
TO THE DIFFERENT SITES NOT

3426
02:08:54,920 --> 02:08:56,840
PROTECTED NOR ANY MICE THAT

3427
02:08:56,840 --> 02:08:59,600
DIDN'T HAVE ANY RESIDENT MEMORY

3428
02:08:59,600 --> 02:09:01,880
SO THAT THIS IS SHOWN TO

3429
02:09:01,880 --> 02:09:04,000
MULTIPLE PATHOGENS TISSUE

3430
02:09:04,000 --> 02:09:06,840
RESIDENT MEMORY IN FACT CAN

3431
02:09:06,840 --> 02:09:09,560
MEDIATE VERY EFFICIENT

3432
02:09:09,560 --> 02:09:10,520
PROTECTION.

3433
02:09:10,520 --> 02:09:12,080
WE HAVE LOOKED INTO MECHANISMS

3434
02:09:12,080 --> 02:09:14,440
FOR THIS AND SO ON THE RIGHT

3435
02:09:14,440 --> 02:09:16,840
PANEL IN THE LUNG TRM OR TISSUE

3436
02:09:16,840 --> 02:09:19,000
RESIDENT MEMORY CAN BOTH

3437
02:09:19,000 --> 02:09:21,640
PROLIFERATE IN SITU AS WELL AS

3438
02:09:21,640 --> 02:09:23,800
SEND SIGNALS AND RECRUIT AND

3439
02:09:23,800 --> 02:09:26,320
MOBILIZE A VERY EFFICIENT IMMUNE

3440
02:09:26,320 --> 02:09:28,080
RESPONSE FROM THAT LYMPH NODE SO

3441
02:09:28,080 --> 02:09:31,520
THIS COORDINATED LOCALIZED

3442
02:09:31,520 --> 02:09:33,760
RESPONSE AT THAT SITE BETWEEN

3443
02:09:33,760 --> 02:09:36,840
LUNG AND LUNG LYMPH NODE NEXT

3444
02:09:36,840 --> 02:09:37,240
SLIDE.

3445
02:09:37,240 --> 02:09:39,040
SO KNOWING THAT THE TISSUE

3446
02:09:39,040 --> 02:09:40,840
RESIDENT MEMORY CELLS WERE

3447
02:09:40,840 --> 02:09:42,040
PROTECTIVE ONES WE WANTED TO

3448
02:09:42,040 --> 02:09:45,640
FIND A WAY TO EXAMINE, TO

3449
02:09:45,640 --> 02:09:49,200
INVESTIGATE TRN IN HUMAN SO WE

3450
02:09:49,200 --> 02:09:51,960
SET UP AN ORGAN DONOR RESOURCE

3451
02:09:51,960 --> 02:09:53,600
TO GET MULTIPLE TISSUES FROM

3452
02:09:53,600 --> 02:09:55,840
ORGAN DONORS WE DID THIS OVER 11

3453
02:09:55,840 --> 02:09:56,240
YEARS AGO.

3454
02:09:56,240 --> 02:09:58,320
IT WAS THROUGH THE INITIAL

3455
02:09:58,320 --> 02:10:00,000
SUPPORT OF A CHALLENGE GRANT

3456
02:10:00,000 --> 02:10:04,360
FROM THE NIAID.

3457
02:10:04,360 --> 02:10:07,680
WE HAVE A RANGEMENT WITH THE

3458
02:10:07,680 --> 02:10:09,200
LOCAL ORGANIZATION FROM BRAIN

3459
02:10:09,200 --> 02:10:11,120
DEAD ORGAN DONORS TO CONSENT TO

3460
02:10:11,120 --> 02:10:13,440
USE TISSUES OR ORGANS FOR LIFE

3461
02:10:13,440 --> 02:10:15,840
SAVING TRANSPLANTATION AND SOME

3462
02:10:15,840 --> 02:10:18,200
ALSO CONSENT TO USE OF ACTIVE

3463
02:10:18,200 --> 02:10:18,640
TISSUES FOR RESEARCH.

3464
02:10:18,640 --> 02:10:21,480
ALL THE RESEARCH ORGAN VARIANTS

3465
02:10:21,480 --> 02:10:22,760
THAT WE HAVE TISSUE SO WE GET

3466
02:10:22,760 --> 02:10:25,720
ALL THE SITES, MANY AS 15 TO 20

3467
02:10:25,720 --> 02:10:28,000
SITES INCLUDING A REAL FOCUS ON

3468
02:10:28,000 --> 02:10:29,680
MUCOSAL SITES, ALL THE DRAINING

3469
02:10:29,680 --> 02:10:31,800
AND ASSOCIATED LYMPH NODES WITH

3470
02:10:31,800 --> 02:10:33,680
THESE SITES, PERIPHERAL LYMPH

3471
02:10:33,680 --> 02:10:36,240
NODES, SPLEEN, BONE MARROW,

3472
02:10:36,240 --> 02:10:38,120
TONSIL THYMUS, MULTIPLE TISSUE

3473
02:10:38,120 --> 02:10:39,040
SITES.

3474
02:10:39,040 --> 02:10:40,520
AND THE OTHER ADVANTAGE OF USING

3475
02:10:40,520 --> 02:10:44,560
ORGAN DONORS IS THEY ARE

3476
02:10:44,560 --> 02:10:46,840
PREVIOUSLY (INAUDIBLE) DISEASE

3477
02:10:46,840 --> 02:10:51,320
OR CANCER FREE ARE NOW PCR

3478
02:10:51,320 --> 02:10:53,040
TESTED AS WELL SO ONLY TAKE ONES

3479
02:10:53,040 --> 02:10:54,360
THAT AREN'T HAVING ACTIVE

3480
02:10:54,360 --> 02:10:55,520
INFECTION AND WE GET THEM FROM

3481
02:10:55,520 --> 02:10:59,840
ALL AGES OF LIFE, AND YOU CAN

3482
02:10:59,840 --> 02:11:01,960
SEE WE REPRESENT MOST OF ADULT

3483
02:11:01,960 --> 02:11:05,040
AGES PRACTICALLY ALL AGE OF LIFE

3484
02:11:05,040 --> 02:11:07,440
UP UNTIL TENTH DECADE.

3485
02:11:07,440 --> 02:11:10,000
THEN WE HAVE ANOTHER RESOURCE WE

3486
02:11:10,000 --> 02:11:12,040
CAN ALSO GET SAMPLES FROM

3487
02:11:12,040 --> 02:11:14,440
PEDIATRIC ORGAN DONOR, THIS IS

3488
02:11:14,440 --> 02:11:15,560
THROUGH THE N POND, THIS IS

3489
02:11:15,560 --> 02:11:21,040
ACTUALLY SET UP THROUGH THE

3490
02:11:21,040 --> 02:11:22,840
CHARITABLE TRUST WHERE WE GET

3491
02:11:22,840 --> 02:11:24,120
MULTIPLE ORGAN DONORS.

3492
02:11:24,120 --> 02:11:25,840
SO WE USE THE ORGAN DONORS TO

3493
02:11:25,840 --> 02:11:27,640
CHARACTERIZE AND MAP T-CELL

3494
02:11:27,640 --> 02:11:32,600
IMMUNITY AS WELL AS OTHER IMMUNE

3495
02:11:32,600 --> 02:11:37,400
CELLS, IN THROUGHOUT THROUGHOUT

3496
02:11:37,400 --> 02:11:38,000
LIFE AND DIFFERENT TISSUES.

3497
02:11:38,000 --> 02:11:42,520
TO TELL YOU TRM YOU CAN SEE

3498
02:11:42,520 --> 02:11:43,800
BLOOD AT TOP TISSUE AT THE

3499
02:11:43,800 --> 02:11:44,320
BOTTOM.

3500
02:11:44,320 --> 02:11:46,520
TRM CONSTITUTE MAJORITY OF

3501
02:11:46,520 --> 02:11:49,240
MEMORY CELLS AND T-CELLS, IN

3502
02:11:49,240 --> 02:11:52,480
BOTH INTESTINES LUNGS AND EVEN

3503
02:11:52,480 --> 02:11:55,440
OUR LYMPHOID TISSUE NOT IN

3504
02:11:55,440 --> 02:11:58,520
BLOOD, AND THAT WE HAVE SHOWN BY

3505
02:11:58,520 --> 02:12:00,600
MULTIPLE CHARACTERIZATION THAT

3506
02:12:00,600 --> 02:12:07,400
THE PHENOTYPE AT CD 69 AND/OR CD

3507
02:12:07,400 --> 02:12:08,040
103 REPRESENT TRANSCRIPTIONALLY

3508
02:12:08,040 --> 02:12:10,440
DISTINCT SUBSET OF TRM, I WON'T

3509
02:12:10,440 --> 02:12:12,280
GO OVER THE FEATURES BUT

3510
02:12:12,280 --> 02:12:13,680
MULTIPLE WE IDENTIFIED THROUGH

3511
02:12:13,680 --> 02:12:14,680
SINGLE CELL PROFILING.

3512
02:12:14,680 --> 02:12:15,320
NEXT SLIDE.

3513
02:12:15,320 --> 02:12:16,640
BUT WHAT I WOULD LIKE TO

3514
02:12:16,640 --> 02:12:18,760
DESCRIBE TO YOU TODAY ARE

3515
02:12:18,760 --> 02:12:20,240
INVESTIGATIONS USING THESE

3516
02:12:20,240 --> 02:12:22,200
TISSUES TO UNDERSTAND ANTIVIRAL

3517
02:12:22,200 --> 02:12:24,200
AND VACCINE IMMUNITY.

3518
02:12:24,200 --> 02:12:26,920
SO WE LOOKED AT T-CELL SPECIFIC

3519
02:12:26,920 --> 02:12:30,080
FOR DIFFERENT VIRUSES, INCLUDING

3520
02:12:30,080 --> 02:12:33,120
FROM A NUMBER OF COHORT ACROSS

3521
02:12:33,120 --> 02:12:34,240
AGE AND PROBABLY THE LARGEST WE

3522
02:12:34,240 --> 02:12:36,800
HAVE DONE IS FLU AN CMV.

3523
02:12:36,800 --> 02:12:39,840
AND FLU IS OF COURSE

3524
02:12:39,840 --> 02:12:41,240
UBIQUITOUS@PATHWAY, MULTIPLE DI

3525
02:12:41,240 --> 02:12:44,680
CLOSURES OVER YOUR LIFETIME,

3526
02:12:44,680 --> 02:12:46,920
CYTOMEGALY VIRUS IS CONTINUOUS

3527
02:12:46,920 --> 02:12:48,640
EXPOSURE OR AT LEAST CONTINUOUS

3528
02:12:48,640 --> 02:12:51,040
CONTROL AND COMPARING MORE

3529
02:12:51,040 --> 02:12:53,360
RECENTLY TO SMALLER COHORT OF

3530
02:12:53,360 --> 02:12:55,360
DONORS BUT THIS IS GROWK TO SARS

3531
02:12:55,360 --> 02:12:57,200
COV-2 INFECTION AND ALSO TO THE

3532
02:12:57,200 --> 02:12:57,800
VACCINATION.

3533
02:12:57,800 --> 02:12:59,280
SO WE LOOK AT DISTRIBUTION OF

3534
02:12:59,280 --> 02:13:01,040
MEMORY CELLS ACROSS TISSUE,

3535
02:13:01,040 --> 02:13:02,240
WHETHER THEY ARE CIRCULATING ON

3536
02:13:02,240 --> 02:13:04,840
RESIDENT AND FACTORS FOR WHAT

3537
02:13:04,840 --> 02:13:05,920
TERMS WHETHER THEY ARE

3538
02:13:05,920 --> 02:13:07,840
CIRCULATING OR WHERE WHERE THEY

3539
02:13:07,840 --> 02:13:12,600
ARE AND WE ALSO IN COLLABORATION

3540
02:13:12,600 --> 02:13:18,040
WITH CROTTI TO MEMORY B CELL AND

3541
02:13:18,040 --> 02:13:18,880
TISSUE RESIDENT.

3542
02:13:18,880 --> 02:13:21,240
SO IN RESPONSE TO -- WHEN WE

3543
02:13:21,240 --> 02:13:23,760
LOOK AT RESPONSES TO UBIQUITOUS

3544
02:13:23,760 --> 02:13:25,120
PATHOGENS PRE-PANDEMIC STUDIES

3545
02:13:25,120 --> 02:13:29,320
AND ALSO DURING THE PANDEMIC, WE

3546
02:13:29,320 --> 02:13:31,720
USED MULTIPLE WE KNOW HLA TYPE

3547
02:13:31,720 --> 02:13:33,280
AND ROLE OF DONORS AND WE CAN

3548
02:13:33,280 --> 02:13:34,640
ASK WHERE INFLUENZA SPECIFIC

3549
02:13:34,640 --> 02:13:36,000
MEMORY ON THE TOP ROW, THAT IS

3550
02:13:36,000 --> 02:13:38,280
ONE PERSON, AND ALL THE

3551
02:13:38,280 --> 02:13:39,040
DIFFERENT TISSUES AND WE ARE

3552
02:13:39,040 --> 02:13:41,400
SEEING THE FLU AND THE CMV

3553
02:13:41,400 --> 02:13:43,640
SPECIFIC MEMORY IN THE LOWER

3554
02:13:43,640 --> 02:13:44,120
ROW.

3555
02:13:44,120 --> 02:13:46,440
OBESE THE MEMORY T-CELLS ARE ALL

3556
02:13:46,440 --> 02:13:48,280
MEMORY CD8 OTHER INFECTION

3557
02:13:48,280 --> 02:13:50,640
EPITOPE, MOSTLY CONCENTRATED IN

3558
02:13:50,640 --> 02:13:52,640
THE LUNG AND THE (INAUDIBLE) IS

3559
02:13:52,640 --> 02:13:54,440
LUNG ASSOCIATED LYMPH NODE.

3560
02:13:54,440 --> 02:13:56,720
MLM IS GUT MESSENGER LYMPH NODE

3561
02:13:56,720 --> 02:13:59,160
WHEREAS CMV SPECIFIC T-CELLS ARE

3562
02:13:59,160 --> 02:14:00,400
DISTRIBUTED IN MULTIPLE SITES.

3563
02:14:00,400 --> 02:14:02,360
AND WHEN YOU LOOK AT THE LEFT IN

3564
02:14:02,360 --> 02:14:05,160
THE -- IN TERMS OF TRM, THAT THE

3565
02:14:05,160 --> 02:14:07,240
MAJORITY OF MEMORY T-CELLS IN

3566
02:14:07,240 --> 02:14:10,840
THE LUNG EVEN UP TO 80%,

3567
02:14:10,840 --> 02:14:12,480
SPECIFIC ONES ARE TRM

3568
02:14:12,480 --> 02:14:13,960
PHENOTYPING WE FOUND SIGNIFICANT

3569
02:14:13,960 --> 02:14:15,920
TRM IN LUNG ASSOCIATED IN THE

3570
02:14:15,920 --> 02:14:16,360
SPLEEN.

3571
02:14:16,360 --> 02:14:18,680
AND THERE'S DIFFERENT FACTORS

3572
02:14:18,680 --> 02:14:21,400
THAT GOVERN THIS AND ONE IS

3573
02:14:21,400 --> 02:14:22,920
ACTUALLY -- SO MALES TEND TO

3574
02:14:22,920 --> 02:14:26,240
HAVE MORE TRM FORGIVEN SITE THAN

3575
02:14:26,240 --> 02:14:28,560
FEMALES AND FEMALES MORE

3576
02:14:28,560 --> 02:14:28,960
CIRCULATING.

3577
02:14:28,960 --> 02:14:30,600
TYPE OF RESPONSES BOTH TO FLU

3578
02:14:30,600 --> 02:14:32,240
AND CMV WHICH IS IN THE STUDY

3579
02:14:32,240 --> 02:14:33,960
THAT WAS PUBLISHED A FEW MONTHS

3580
02:14:33,960 --> 02:14:36,800
AGO IN CELL REPORT AND THEN

3581
02:14:36,800 --> 02:14:38,840
CLICK -- WE ALSO LOOKED AT AGE

3582
02:14:38,840 --> 02:14:42,600
AND DIFFERENT FACTORS IN AGE,

3583
02:14:42,600 --> 02:14:44,880
AND THERE IS ACTUALLY TWO

3584
02:14:44,880 --> 02:14:46,600
REGULATION WITH AGE, ONE IS

3585
02:14:46,600 --> 02:14:48,120
WHETHER A CHILD VERSUS ADULT, SO

3586
02:14:48,120 --> 02:14:50,320
IF YOU LOOK AT TRM AND FLU

3587
02:14:50,320 --> 02:14:51,800
SPECIFIC TRM IN A CHILD ON THE

3588
02:14:51,800 --> 02:14:53,840
LEFT AND ADULT ON THE RIGHT, THE

3589
02:14:53,840 --> 02:14:54,840
CHILDREN HAVE A LOWER FREQUENCY

3590
02:14:54,840 --> 02:14:59,680
OF TRM SPECIFICALLY FOR ADULT.

3591
02:14:59,680 --> 02:15:02,000
THAT IS LUNG ASSOCIATED LYMPH

3592
02:15:02,000 --> 02:15:03,680
NODE, THAT MAY BE DUE TO NOT

3593
02:15:03,680 --> 02:15:05,560
HAVING EXPOSURE, THAT'S ONE

3594
02:15:05,560 --> 02:15:06,160
HYPOTHESIS.

3595
02:15:06,160 --> 02:15:08,040
BUT OVER ADULT LIFE IT IS PRETTY

3596
02:15:08,040 --> 02:15:10,440
STEADY IN THE LUNG, BUT IT DOES

3597
02:15:10,440 --> 02:15:12,120
DECLINE IN LUNG BARING LYMPH

3598
02:15:12,120 --> 02:15:15,040
NODES AND JUST LYMPH NODES DO

3599
02:15:15,040 --> 02:15:15,680
UNDERGO AGING.

3600
02:15:15,680 --> 02:15:18,640
YOU HAVE FEWER OF THEN, THEY

3601
02:15:18,640 --> 02:15:19,840
UNDERGO FIBROTIC CHANGES OVER

3602
02:15:19,840 --> 02:15:22,560
AGE SO HA IS MANIFEST DECLINE.

3603
02:15:22,560 --> 02:15:23,960
MENTION SLIDE.

3604
02:15:23,960 --> 02:15:27,280
BUT WHAT ABOUT IN RESPONSE TO A

3605
02:15:27,280 --> 02:15:27,840
PATHOGEN?

3606
02:15:27,840 --> 02:15:30,240
THIS IS A STUDY WE DID IN

3607
02:15:30,240 --> 02:15:32,360
COLLABORATION WITH CROTTI'S LAB

3608
02:15:32,360 --> 02:15:34,760
AND ALSO ALEX SETTI, WE HAD FOUR

3609
02:15:34,760 --> 02:15:37,080
ORGAN DONORS WE GOT MULTIPLE

3610
02:15:37,080 --> 02:15:39,640
TISSUES FROM WHO HAD PREVIOUS

3611
02:15:39,640 --> 02:15:41,200
INFECTION, AND EITHER FROM TWO

3612
02:15:41,200 --> 02:15:42,960
MONTHS TO SIX MONTHS POST

3613
02:15:42,960 --> 02:15:44,240
INFECTION YOU CAN SEE ONE CHILD

3614
02:15:44,240 --> 02:15:47,120
AND THREE ADULT, SO WE DID IS WE

3615
02:15:47,120 --> 02:15:49,720
ASKED TO FIND THESE MEMORY SARS

3616
02:15:49,720 --> 02:15:50,960
COV-2 SPECIFIC MEMORY CELLS AND

3617
02:15:50,960 --> 02:15:53,240
MULTIPLE SITES, WE DID THE AMASA

3618
02:15:53,240 --> 02:15:55,880
ON THE LEFT AND YOU CAN SEE WE

3619
02:15:55,880 --> 02:15:59,640
ALSO HAVE BLOOD THAT WE FOUND,

3620
02:15:59,640 --> 02:16:01,800
THESE SPIKES SPECIFIC CENTER

3621
02:16:01,800 --> 02:16:03,800
COLUMN, T-CELLS IN MULTIPLE

3622
02:16:03,800 --> 02:16:05,040
SITES INCLUDING THE LUNG

3623
02:16:05,040 --> 02:16:06,280
ASSOCIATED LYMPH NODE, CLICK

3624
02:16:06,280 --> 02:16:07,480
AGAIN.

3625
02:16:07,480 --> 02:16:08,880
THEN WE COMBINED IT FROM

3626
02:16:08,880 --> 02:16:11,240
MULTIPLE DONORS AND ACROSS YOU

3627
02:16:11,240 --> 02:16:14,080
CAN SEE THAT FOR CD4 ON THE TOP

3628
02:16:14,080 --> 02:16:16,520
ROW AND CD8 BOTTOM IS THERE WERE

3629
02:16:16,520 --> 02:16:17,480
SIGNIFICANT FREQUENCIES IN THE

3630
02:16:17,480 --> 02:16:19,200
HIGHEST IN THE LUNG AND THE LUNG

3631
02:16:19,200 --> 02:16:21,400
ASSOCIATED LYMPH NODES AND ALSO

3632
02:16:21,400 --> 02:16:23,640
PRETTY GOOD NUMBERS IN GUT

3633
02:16:23,640 --> 02:16:25,800
ASSOCIATED LYMPH NODES FOR CD4

3634
02:16:25,800 --> 02:16:29,360
AND CD8 AND INTERESTINGLY FOR

3635
02:16:29,360 --> 02:16:32,040
TRM PHENOTYPE WE FOUND TRM FOR

3636
02:16:32,040 --> 02:16:34,640
CD4 IN THE LUNG AND TRM CD8 IN

3637
02:16:34,640 --> 02:16:36,240
LUNG AN LUNG ASSOCIATED LYMPH

3638
02:16:36,240 --> 02:16:38,840
NODE AND GUT ASSOCIATE
ASSOCIATED LIMB

3639
02:16:38,840 --> 02:16:42,040
NODE SO WE ARE GENERATING SARS

3640
02:16:42,040 --> 02:16:43,120
COV-2 INFECTION THOUGH

3641
02:16:43,120 --> 02:16:45,040
PROPORTION IS LOWER THAN YOU SEE

3642
02:16:45,040 --> 02:16:45,480
WITH FLU.

3643
02:16:45,480 --> 02:16:51,800
NEXT SLIDE.  SO THEN SHANE'S LAB

3644
02:16:51,800 --> 02:16:52,960
AND ALEX'S WITH KAY TOE AND

3645
02:16:52,960 --> 02:16:54,800
SHANE COTY'S LAB HE TOOK CAM

3646
02:16:54,800 --> 02:16:56,640
SAMPLES AND LOOK AT MEMORY B

3647
02:16:56,640 --> 02:16:58,840
CELLS IN THESE DIFFERENT TISSUES

3648
02:16:58,840 --> 02:17:00,280
YOU CAN SEE IN THE PANEL ON THE

3649
02:17:00,280 --> 02:17:02,160
LEFT IS THAT YOU HAVE MULTIPLE

3650
02:17:02,160 --> 02:17:04,280
SITES THAT HAVE SARS COV-2

3651
02:17:04,280 --> 02:17:05,800
MEMORY B CELLS AND IT IS REALLY

3652
02:17:05,800 --> 02:17:08,840
ACROSS ESPECIALLY IN THE LUNG

3653
02:17:08,840 --> 02:17:12,080
ASSOCIATED LYMPH NODE YOU SEE IN

3654
02:17:12,080 --> 02:17:13,120
PILE NICE FREQUENCY, HIGH

3655
02:17:13,120 --> 02:17:15,240
FREQUENCIES IN ALL DONORS WHO

3656
02:17:15,240 --> 02:17:17,440
PREVIOUSLY INFECTED IN LUNG,

3657
02:17:17,440 --> 02:17:19,440
LUNG ASSOCIATED LYMPH NODE AND

3658
02:17:19,440 --> 02:17:22,280
WE LOOK AT CD 69 EXPRESSION WITH

3659
02:17:22,280 --> 02:17:24,040
MARKED TISSUE RESONANT MEMORY B

3660
02:17:24,040 --> 02:17:25,520
CELLS, WHAT YOU CAN SEE IS IF

3661
02:17:25,520 --> 02:17:27,280
YOU LOOK AT THE CD 69 EXPRESSION

3662
02:17:27,280 --> 02:17:28,440
PARTICULARLY IN THE LYMPH NODE

3663
02:17:28,440 --> 02:17:30,840
IS WHERE WE REALLY FOUND AND

3664
02:17:30,840 --> 02:17:32,240
LUNG FOUND HIGH FREQUENCY OF

3665
02:17:32,240 --> 02:17:34,160
SARS COV-2 SPECIFIC MEMORY B

3666
02:17:34,160 --> 02:17:38,360
CELLS EXPRESSING CD 69.

3667
02:17:38,360 --> 02:17:39,840
BUT NOT BONE MARROW SPLEEN.

3668
02:17:39,840 --> 02:17:41,640
YOU LOOK AT THE PILE IT PEAKS IN

3669
02:17:41,640 --> 02:17:43,200
THE LUNG AND ALSO IN THE LYMPH

3670
02:17:43,200 --> 02:17:44,920
NODE BUT NOT IN THE BONE OR

3671
02:17:44,920 --> 02:17:48,240
SPLEEN SO WE ARE GENERATING

3672
02:17:48,240 --> 02:17:50,520
RESIDENT MEMORY B CELLS, MEMORY

3673
02:17:50,520 --> 02:17:52,040
RESIDENT T-CELLS AT SITE OF

3674
02:17:52,040 --> 02:17:53,480
INFECTION IN THE LUNG AND ALSO

3675
02:17:53,480 --> 02:17:54,840
LYMPH NODES INCLUDING GUT

3676
02:17:54,840 --> 02:17:57,080
ASSOCIATED LYMPH NODE, THERE IS

3677
02:17:57,080 --> 02:17:58,640
SOME SUPPORT THAT SARS COV-2

3678
02:17:58,640 --> 02:18:00,920
VIRUS INFECTS THE LUNG.

3679
02:18:00,920 --> 02:18:02,320
THE GUT SO THAT COULD BE RELATED

3680
02:18:02,320 --> 02:18:02,880
TO THAT.

3681
02:18:02,880 --> 02:18:04,120
NEXT SLIDE.

3682
02:18:04,120 --> 02:18:06,640
SO WE ALSO LOOKED AT SOME OTHER

3683
02:18:06,640 --> 02:18:09,600
PROPERTIES OF THESE CELLS AND

3684
02:18:09,600 --> 02:18:13,120
WHAT ALICE FOUND IS THAT IN FACT

3685
02:18:13,120 --> 02:18:14,680
THERE WAS SARS COV-2 SPECIFIC

3686
02:18:14,680 --> 02:18:16,560
MEMORY B CELLS IN THREE OF THE

3687
02:18:16,560 --> 02:18:20,600
FOUR DONORS INCLUDING THE CHILD,

3688
02:18:20,600 --> 02:18:22,200
EXHIBIT PHENOTYPE OF GERMINAL

3689
02:18:22,200 --> 02:18:24,280
CENTER B CELL AND THAT IS

3690
02:18:24,280 --> 02:18:25,680
SPECIFICALLY IN THE LUNG

3691
02:18:25,680 --> 02:18:27,480
ASSOCIATED LYMPH NODE.

3692
02:18:27,480 --> 02:18:30,840
WE WILL ALSO FOUND WE ALSO FOUND

3693
02:18:30,840 --> 02:18:33,160
IN THE SARS COV-2 SPECIFIC

3694
02:18:33,160 --> 02:18:34,640
T-CELLS IN THE LUNG ASSOCIATED

3695
02:18:34,640 --> 02:18:35,800
LYMPH NODE AND THE GUT

3696
02:18:35,800 --> 02:18:38,440
ASSOCIATED LYMPH NODE WE FOUND T

3697
02:18:38,440 --> 02:18:39,800
FOLLICULAR HELPER CELL

3698
02:18:39,800 --> 02:18:41,760
PHENOTYPES AND ALSO ONE DONOR IN

3699
02:18:41,760 --> 02:18:42,040
THE LUNG.

3700
02:18:42,040 --> 02:18:44,880
SO WE ARE GENERAL -- THERE IS

3701
02:18:44,880 --> 02:18:46,760
EVIDENCE FOR ONGOING OR

3702
02:18:46,760 --> 02:18:49,640
PERSISTENT GERMINAL CENTER

3703
02:18:49,640 --> 02:18:52,040
REACTIONS TO SARS COV-2.

3704
02:18:52,040 --> 02:18:52,360
NEXT SLIDE.

3705
02:18:52,360 --> 02:18:55,280
SO THAT IS INFECTION.

3706
02:18:55,280 --> 02:18:56,000
WHAT ABOUT mRNA VACCINATION?

3707
02:18:56,000 --> 02:18:58,160
WE HAVE -- THIS IS VERY MUCH

3708
02:18:58,160 --> 02:18:59,440
WORK IN PROGRESS SHOWING YOU

3709
02:18:59,440 --> 02:19:01,360
SOME NEW DATA.

3710
02:19:01,360 --> 02:19:02,520
FOR COMPARISON.

3711
02:19:02,520 --> 02:19:05,800
WE HAVE EIGHT DOE NO, SIR AGE

3712
02:19:05,800 --> 02:19:08,120
33-75, VACCINATED WITH TWO DOSES

3713
02:19:08,120 --> 02:19:10,560
OF mRNA BETWEEN ONE AND SIX

3714
02:19:10,560 --> 02:19:11,440
MONTHS.

3715
02:19:11,440 --> 02:19:13,120
WE ARE ONLY GETTING DONORS SO WE

3716
02:19:13,120 --> 02:19:14,520
ASKED THE TRANSPLANTS

3717
02:19:14,520 --> 02:19:15,520
COORDINATORS TO ASK ABOUT

3718
02:19:15,520 --> 02:19:16,160
VACCINE HISTORY.

3719
02:19:16,160 --> 02:19:18,120
THESE ARE DONORS WE ARE SURE OF

3720
02:19:18,120 --> 02:19:19,640
VACCINE HISTORY, THEY ALL HAVE

3721
02:19:19,640 --> 02:19:21,760
THE VACCINATED DONORS,

3722
02:19:21,760 --> 02:19:23,760
VACCINATED TWICE, HAVE GOOD

3723
02:19:23,760 --> 02:19:25,640
ANTIBODY RESPONSES TO SPIKE.

3724
02:19:25,640 --> 02:19:27,880
BUT WHAT ABOUT THEIR T-CELL, SO

3725
02:19:27,880 --> 02:19:30,000
THE T-CELLS WITH CD4 ON THE TOP

3726
02:19:30,000 --> 02:19:33,640
AND CD8 BOTTOM, THE COLORS ARE

3727
02:19:33,640 --> 02:19:35,080
ALL VACCINATED AND PRE-PANDEMIC

3728
02:19:35,080 --> 02:19:36,440
CONTROLS THE LYMPH NODE, THAT IS

3729
02:19:36,440 --> 02:19:38,040
A LUNG ASSOCIATED ON THE LEFT,

3730
02:19:38,040 --> 02:19:39,920
THAT IS THE HIGHEST RESPONSE BUT

3731
02:19:39,920 --> 02:19:41,720
IT REALLY VARY, IT IS A WIDE

3732
02:19:41,720 --> 02:19:43,840
RANGE AND I PUT WHERE THE MEAN

3733
02:19:43,840 --> 02:19:45,320
RESPONSE IS FOR INFECTION ON

3734
02:19:45,320 --> 02:19:46,880
BOTH OF THESE SO IT IS A LITTLE

3735
02:19:46,880 --> 02:19:49,080
BIT MORE VARIABLE AND ALSO

3736
02:19:49,080 --> 02:19:49,600
LOWER.

3737
02:19:49,600 --> 02:19:53,240
SO AGAIN THE PHENOTYPE OF THESE

3738
02:19:53,240 --> 02:20:02,120
T-CELLS IS MEMORY TEM BUT

3739
02:20:02,120 --> 02:20:04,960
MEMORY, CENTRAL MEMORY, T

3740
02:20:04,960 --> 02:20:06,760
FOLLICULAR HELPER CELL IN LONG

3741
02:20:06,760 --> 02:20:08,600
DRAINING LYMPH NODE AND THEN WE

3742
02:20:08,600 --> 02:20:10,080
LOOK AT B CELL NEXT SLIDE WHAT

3743
02:20:10,080 --> 02:20:14,040
WE FIND IS THE SPIKED RBD

3744
02:20:14,040 --> 02:20:15,320
SPECIFIC B CELLS YOU CAN DETECT

3745
02:20:15,320 --> 02:20:17,080
THEM IN THE -- THIS IS LYMPH

3746
02:20:17,080 --> 02:20:18,760
NODE ON THE RIGHT OF THE

3747
02:20:18,760 --> 02:20:20,080
VACCINATED PRE-PANDEMICK YOU

3748
02:20:20,080 --> 02:20:21,400
DON'T SEE THEM AND WE DO FIND

3749
02:20:21,400 --> 02:20:23,040
THEM IN THE LUNG DRAINING LYMPH

3750
02:20:23,040 --> 02:20:24,560
NODE THE BONE MARROW AND SPLEEN

3751
02:20:24,560 --> 02:20:26,400
TO LESSER EXTENT AND OF COURSE

3752
02:20:26,400 --> 02:20:27,440
BLOOD.

3753
02:20:27,440 --> 02:20:30,320
WHAT WE ALSO FIND IS THE B CELLS

3754
02:20:30,320 --> 02:20:32,120
IN LUNG DRAINING LYMPH NODE

3755
02:20:32,120 --> 02:20:34,200
LARGE PROPORTION OF THEM ARE CD

3756
02:20:34,200 --> 02:20:35,640
69 TO RESIDENT MEMORY B CELLS,

3757
02:20:35,640 --> 02:20:38,560
THAT WAS REALLY QUITE

3758
02:20:38,560 --> 02:20:39,640
SIGNIFICANT IN THE LUNG DRAINING

3759
02:20:39,640 --> 02:20:40,720
LYMPH NODE OVER ALL THE OTHER

3760
02:20:40,720 --> 02:20:41,240
SITES.

3761
02:20:41,240 --> 02:20:43,640
FOR THE LUNG, VACCINATED, WE

3762
02:20:43,640 --> 02:20:44,960
DON'T FIND THAT MEASURABLE

3763
02:20:44,960 --> 02:20:47,160
RESPONSES BUT WE ARE REDOING

3764
02:20:47,160 --> 02:20:47,800
THOSE AGAIN.

3765
02:20:47,800 --> 02:20:49,120
AND OF COURSE WE WILL HAVE

3766
02:20:49,120 --> 02:20:50,840
OTHERS AND THESE B CELLS ARE NOT

3767
02:20:50,840 --> 02:20:52,360
GERMINAL CENTER SO THERE IS A

3768
02:20:52,360 --> 02:20:53,840
GERMINAL CENTER OF LUNG DRAINING

3769
02:20:53,840 --> 02:20:55,560
LYMPH NODE REPRESENTATIVE OF

3770
02:20:55,560 --> 02:20:57,600
VERY RARE TO FIND NATURALLY

3771
02:20:57,600 --> 02:20:58,960
OCCURRING GERMINAL CENTERS AND

3772
02:20:58,960 --> 02:21:00,640
ANTIGEN SPECIFIC CELLS DO NOT

3773
02:21:00,640 --> 02:21:01,520
HAVE GERMINAL CENTERS.

3774
02:21:01,520 --> 02:21:02,120
NEXT SLIDE.

3775
02:21:02,120 --> 02:21:05,840
TO SUMMARIZE, SO IF YOU LOOK AT

3776
02:21:05,840 --> 02:21:08,440
IN TERMS OF GENERATION OF TISSUE

3777
02:21:08,440 --> 02:21:09,360
RESIDENT VACCINATION, WHAT WE

3778
02:21:09,360 --> 02:21:11,760
ARE SAMPLING IS IN THE BLOOD,

3779
02:21:11,760 --> 02:21:13,320
BUT WE THINK IT IS IMPORTANT TO

3780
02:21:13,320 --> 02:21:15,320
ALSO LOOK AT WHAT SUPPORTING IT

3781
02:21:15,320 --> 02:21:17,480
WHAT IS BEHIND THEM WHAT LIES

3782
02:21:17,480 --> 02:21:18,840
WITHIN IN OUR TISSUES.

3783
02:21:18,840 --> 02:21:21,640
AND HOW THAT MIGHT SUPPORT AND

3784
02:21:21,640 --> 02:21:25,120
CONTRIBUTE TO WHAT YOU SEE IN

3785
02:21:25,120 --> 02:21:28,520
BLOOD SO SITE SPECIFIC VIRUSES

3786
02:21:28,520 --> 02:21:30,440
GENERATE SURVEYING T-CELL

3787
02:21:30,440 --> 02:21:32,040
IMMUNITY AND THE TUMORRER

3788
02:21:32,040 --> 02:21:34,240
PERSISTENCE VARIES WITH EXPOSURE

3789
02:21:34,240 --> 02:21:35,880
AGE SEX AND ROUTE AND WE DOING

3790
02:21:35,880 --> 02:21:37,480
MORE OF THESE TO VIRUSES, SO

3791
02:21:37,480 --> 02:21:41,200
THAT WE CAN ACTUALLY GENERATED

3792
02:21:41,200 --> 02:21:42,840
PREDICTIVE MODELS SO WE CAN SEE

3793
02:21:42,840 --> 02:21:43,920
IF YOUR A FOUR-YEAR-OLD FEMALE

3794
02:21:43,920 --> 02:21:45,480
INFECT WITH A CERTAIN VIRUS WE

3795
02:21:45,480 --> 02:21:47,400
MIGHT BE ABLE TO PREDICT BY

3796
02:21:47,400 --> 02:21:49,080
LOOKING AT TISSUES VERSUS BLOOD

3797
02:21:49,080 --> 02:21:51,200
WHAT RESPONSE YOU ARE GOING TO

3798
02:21:51,200 --> 02:21:51,960
GET.

3799
02:21:51,960 --> 02:21:54,040
SO TUMOR GENERATED TO SARS COV-2

3800
02:21:54,040 --> 02:21:56,120
BUT NOT VACCINES, mRNA

3801
02:21:56,120 --> 02:21:57,040
VACCINES SO FAR.

3802
02:21:57,040 --> 02:21:59,000
BUT LYMPH NODE B RESIDENT MEMORY

3803
02:21:59,000 --> 02:22:01,160
ARE GENERATED TO BOTH SO WE ARE

3804
02:22:01,160 --> 02:22:03,200
HYPOTHESIS TISSUE RESIDENT MAY

3805
02:22:03,200 --> 02:22:05,520
PREDICT THE DURABILITY OF MEMORY

3806
02:22:05,520 --> 02:22:09,360
AND ONE MORE CLICK.

3807
02:22:09,360 --> 02:22:11,520
THAT'S WHY WE WANT PROFILES OF

3808
02:22:11,520 --> 02:22:13,040
CELLULAR MEMORIES AND TISSUES TO

3809
02:22:13,040 --> 02:22:14,600
DURABLE VACCINE SO WE HAVE SOME

3810
02:22:14,600 --> 02:22:17,000
CONTEXT LIKE MEASLES MMR VACCINE

3811
02:22:17,000 --> 02:22:18,640
TO IDENTIFY PARTICULARS OF

3812
02:22:18,640 --> 02:22:20,080
PROTECTION LONGEVITY AND JUST

3813
02:22:20,080 --> 02:22:21,840
LAST SLIDE.

3814
02:22:21,840 --> 02:22:23,880
ACKNOWLEDGE THAT DID THE WORK.

3815
02:22:23,880 --> 02:22:25,560
INCLUDING EVERYONE IN THE LAB,

3816
02:22:25,560 --> 02:22:27,880
THIS IS UNDERTAKING WITH

3817
02:22:27,880 --> 02:22:29,240
SURGEONS AND PEOPLE IN THE LAB

3818
02:22:29,240 --> 02:22:31,840
AND COLLABORATORS WITH LA JOLLA

3819
02:22:31,840 --> 02:22:33,080
INSTITUTE AND SYSTEM BIOLOGIES

3820
02:22:33,080 --> 02:22:34,600
AND COLLABORATORS WITH FLORIDA

3821
02:22:34,600 --> 02:22:36,160
TO GET PEDIATRIC SAMPLES.

3822
02:22:36,160 --> 02:22:41,840
THANKS VERY MUCH.

3823
02:22:41,840 --> 02:22:42,840
>> VERY NICE.

3824
02:22:42,840 --> 02:22:47,320
QUESTIONS FOR DONNA?

3825
02:22:47,320 --> 02:22:47,960
FROM

3826
02:22:47,960 --> 02:22:50,240
>> TURN ON MY VIDEO?

3827
02:22:50,240 --> 02:22:51,440
THEY NOT LETTING ME TURN ON.

3828
02:22:51,440 --> 02:22:51,880
OKAY.

3829
02:22:51,880 --> 02:23:02,240
>> GO I A HEAD.

3830
02:23:02,240 --> 02:23:04,240
QUITE INTERESTING VACCINATION.

3831
02:23:04,240 --> 02:23:06,000
INDICATION OF O RESIDENT MEMORY

3832
02:23:06,000 --> 02:23:08,880
LUNG LYMPH NODE B CELLS AFTER

3833
02:23:08,880 --> 02:23:09,600
SHOT IN THE ARM.

3834
02:23:09,600 --> 02:23:11,880
BUT NOT THE T-CELLS?

3835
02:23:11,880 --> 02:23:17,960
ANY MORE THOUGHTS ON THAT?

3836
02:23:17,960 --> 02:23:19,920
>> IT IS CURIOUS.

3837
02:23:19,920 --> 02:23:21,800
I'M NEW TO B CELLS SO I DIDN'T

3838
02:23:21,800 --> 02:23:25,720
REALLY KNOW WHAT TO EXPECT.

3839
02:23:25,720 --> 02:23:27,320
WE ARE GOING TO LOOK AT OTHER

3840
02:23:27,320 --> 02:23:29,200
LYMPH NODES, SOME PERIPHERAL AND

3841
02:23:29,200 --> 02:23:32,080
WE JUST ASKED PERMISSION TO GET

3842
02:23:32,080 --> 02:23:33,520
DELTOID LYMPH NODE WHICH ARE NOT

3843
02:23:33,520 --> 02:23:34,680
SHOULDER.

3844
02:23:34,680 --> 02:23:37,360
WE CAN'T GET THE AXILLARY LYMPH

3845
02:23:37,360 --> 02:23:39,040
NODE UNDER YOUR ARM, WE WANT TO

3846
02:23:39,040 --> 02:23:40,640
SEE IF WE ARE GETTING IT LIKE

3847
02:23:40,640 --> 02:23:41,840
CLOSER TO THE SITE OF THE

3848
02:23:41,840 --> 02:23:44,320
INJECTION ARE WE GETTING MORE

3849
02:23:44,320 --> 02:23:44,840
RESIDENT MEMORY.

3850
02:23:44,840 --> 02:23:46,840
AND WHAT DO WE FIND RESIDENT

3851
02:23:46,840 --> 02:23:48,600
MEMORY T-CELLS IF WE ARE LITTLE

3852
02:23:48,600 --> 02:23:52,240
BIT CLOSER THE ANTIGEN MIGHT BE

3853
02:23:52,240 --> 02:23:54,400
HIGHER CONCENTRATION IN THAT

3854
02:23:54,400 --> 02:23:54,600
NODE.

3855
02:23:54,600 --> 02:23:58,560
>> DID YOU SAY -- AXILLARY?

3856
02:23:58,560 --> 02:23:59,440
>> NO WE CAN'T.

3857
02:23:59,440 --> 02:24:01,440
WE ARE NOT -- IT IS JUST VERY

3858
02:24:01,440 --> 02:24:02,680
HARD SURGICALLY TO DO, WE ARE

3859
02:24:02,680 --> 02:24:04,040
NOT ALLOWED TO DO EXTRA

3860
02:24:04,040 --> 02:24:08,000
INCISIONS FOR RESEARCH TISSUES. 

3861
02:24:08,000 --> 02:24:10,040
IT IS HARD TO GET THROUGH BUT

3862
02:24:10,040 --> 02:24:11,480
PROBABLY ABLE TO DO IT NEAR THE

3863
02:24:11,480 --> 02:24:15,160
SHOULDER.

3864
02:24:15,160 --> 02:24:17,600
I WONDER IF A LOT OF MEMORY IN B

3865
02:24:17,600 --> 02:24:18,640
CELLS INFLUENCE IS GOING TO BE

3866
02:24:18,640 --> 02:24:19,160
RESIDENT MEMORY.

3867
02:24:19,160 --> 02:24:22,200
I THINK MOST RESIDENT MEMORY IN

3868
02:24:22,200 --> 02:24:24,040
LYMPH NODE'S E MOST B CELL LYMPH

3869
02:24:24,040 --> 02:24:26,080
NODE MEMORY IS GOT TO BE

3870
02:24:26,080 --> 02:24:27,520
(INAUDIBLE).

3871
02:24:27,520 --> 02:24:28,800
>> MARION.

3872
02:24:28,800 --> 02:24:29,640
>> INC. THAT.

3873
02:24:29,640 --> 02:24:31,760
I WAS CURIOUS DONNA, IT WAS

3874
02:24:31,760 --> 02:24:35,280
BEAUTIFUL, THE DIFFERENCE IN THE

3875
02:24:35,280 --> 02:24:36,400
RESIDENCY AFTER VACCINATION.

3876
02:24:36,400 --> 02:24:38,200
DID YOU ALSO SEE DIFFERENCES IN

3877
02:24:38,200 --> 02:24:40,800
FUNCTION LIKE IL 10 PRODUCTION,

3878
02:24:40,800 --> 02:24:42,400
WONDERING IF THAT IS CORRELATED

3879
02:24:42,400 --> 02:24:44,240
TO WHAT WE SEE IN PERIPHERAL

3880
02:24:44,240 --> 02:24:45,080
BLOOD LYMPHOCYTES.

3881
02:24:45,080 --> 02:24:47,680
>> SO WE ARE DOING THOSE

3882
02:24:47,680 --> 02:24:48,240
STUDIES.

3883
02:24:48,240 --> 02:24:51,120
NOW WE DIDN'T -- I MEAN JUST IN

3884
02:24:51,120 --> 02:24:53,240
SORT OF THE CYTOKINE STAINING WE

3885
02:24:53,240 --> 02:24:54,160
DIDN'T SEE CYTOKINE SIGNALING

3886
02:24:54,160 --> 02:24:55,000
WITH THESE.

3887
02:24:55,000 --> 02:24:56,240
SOME ARE VERY LOW.

3888
02:24:56,240 --> 02:24:59,400
AND WE ARE ALSO SWITCHING NOW SO

3889
02:24:59,400 --> 02:25:01,800
THAT INITIAL COHORT WAS ALL WE

3890
02:25:01,800 --> 02:25:03,240
BUILT UP A COHORT WITH FROZEN

3891
02:25:03,240 --> 02:25:04,800
STORED CELLS SO WE ARE ALSO

3892
02:25:04,800 --> 02:25:06,800
GOING TO DO FRESHER CELLS LIKE

3893
02:25:06,800 --> 02:25:08,640
FROM FRESH DONORS SO THAT WE CAN

3894
02:25:08,640 --> 02:25:12,240
MAINTAIN SOME OF THE FUNCTION AS

3895
02:25:12,240 --> 02:25:17,440
WELL.

3896
02:25:17,440 --> 02:25:20,000
>> I HAD A QUESTION YOU ALLUDED

3897
02:25:20,000 --> 02:25:22,000
TO POSSIBLY DIFFERENCE WITH

3898
02:25:22,000 --> 02:25:30,280
MEASLES.

3899
02:25:30,280 --> 02:25:35,160
(LOST AUDIO) ON MEASLES TRMs

3900
02:25:35,160 --> 02:25:36,040
OR IS THAT SOMETHING YOU ARE

3901
02:25:36,040 --> 02:25:36,960
LOOKING AT NOW?

3902
02:25:36,960 --> 02:25:39,640
>> WE ARE LOOKING NOW, WE

3903
02:25:39,640 --> 02:25:44,200
ACTUALLY JUST THROUGH ALEX S

3904
02:25:44,200 --> 02:25:46,640
SEFF'S PEPTIDES, WE JUST GOT A

3905
02:25:46,640 --> 02:25:48,640
BUNCH OF PEPTIDE, WE ALSO ARE

3906
02:25:48,640 --> 02:25:49,520
THEM FOR MUMPS.

3907
02:25:49,520 --> 02:25:50,840
WE HAVE DONE TITERS AND DONORS

3908
02:25:50,840 --> 02:25:53,320
FOR MEASLES AND IT IS STEADY SO

3909
02:25:53,320 --> 02:25:54,680
OLDER PEOPLE HAVE REALLY GREAT

3910
02:25:54,680 --> 02:25:55,720
TITERS FOR MEASLES.

3911
02:25:55,720 --> 02:25:58,040
WE HAVE ALSO DONE FOR MUMPS,

3912
02:25:58,040 --> 02:25:59,040
MUMPS DECLINE AS BIT SO WE ARE

3913
02:25:59,040 --> 02:26:01,240
GOING TO DO THIS WITH KNOWN

3914
02:26:01,240 --> 02:26:02,720
VACCINE SO WE CAN PUT THINGS IN

3915
02:26:02,720 --> 02:26:03,840
CONTEXT.

3916
02:26:03,840 --> 02:26:07,240
BUT IT IS ONGOING.

3917
02:26:07,240 --> 02:26:11,480
>> LAST QUESTION FROM ROSS.

3918
02:26:11,480 --> 02:26:14,160
>> NO ARE YOU DELINEATING

3919
02:26:14,160 --> 02:26:16,040
RESIDENT MEMORY AND TERTIARY

3920
02:26:16,040 --> 02:26:17,240
LYMPH NODE STRUCTURES IN THE

3921
02:26:17,240 --> 02:26:18,440
VARIOUS TISSUES YOU ARE LOOKING

3922
02:26:18,440 --> 02:26:19,840
AGENT, IS THERE A WAY YOU ARE

3923
02:26:19,840 --> 02:26:21,640
CLARIFYING THAT?

3924
02:26:21,640 --> 02:26:23,120
>> YEAH.

3925
02:26:23,120 --> 02:26:25,840
SO MOST OF THE VACCINE IT IS ALL

3926
02:26:25,840 --> 02:26:28,080
IN THE LYMPHOID TISSUES ALREADY

3927
02:26:28,080 --> 02:26:29,880
BUT IN THE LUNG SO IN THE LUNG

3928
02:26:29,880 --> 02:26:31,360
ADULT HUMAN ADULT LUNGS DON'T

3929
02:26:31,360 --> 02:26:37,560
REALLY HAVE A LOT OF -- THE ONLY

3930
02:26:37,560 --> 02:26:39,480
DONORS WE FOUND (INAUDIBLE) IN

3931
02:26:39,480 --> 02:26:43,560
-- SO BABIES AND YOUNG KIDS UP

3932
02:26:43,560 --> 02:26:46,080
TO SIX HAVE FOLLICLES AND THEY

3933
02:26:46,080 --> 02:26:50,040
CAN EVEN GENERATE GERMINAL

3934
02:26:50,040 --> 02:26:51,400
CENTER, ANOTHER STORY WE ARE

3935
02:26:51,400 --> 02:26:54,040
WORKING ON WITH PEDIATRIC DONORS

3936
02:26:54,040 --> 02:26:56,200
BUT IN ADULTS YOU JUST DON'T SEE

3937
02:26:56,200 --> 02:26:56,600
IT.

3938
02:26:56,600 --> 02:26:57,560
YOU DON'T SEE IT IN THE LUNG.

3939
02:26:57,560 --> 02:26:59,880
>> HAS THAT BEEN DONE BEFORE?

3940
02:26:59,880 --> 02:27:01,600
>> THERE IS A REALLY -- SO WE

3941
02:27:01,600 --> 02:27:02,840
STARTED LOOKING AT THIS, THERE

3942
02:27:02,840 --> 02:27:05,440
IS A OLD PAPER LIKE SOME ANATOMY

3943
02:27:05,440 --> 02:27:07,680
JOURNAL WHERE THEY DOCUMENT THAT

3944
02:27:07,680 --> 02:27:10,400
THERE IS BOTH IN YOUNG LUNGS AND

3945
02:27:10,400 --> 02:27:12,160
IN MICE MOUSE LUNGS WHEN YOU

3946
02:27:12,160 --> 02:27:16,560
GIVE THEM LPS, YOU CAN GENERATE

3947
02:27:16,560 --> 02:27:17,080
IT.

3948
02:27:17,080 --> 02:27:19,840
THEY INDUCE NICELY.

3949
02:27:19,840 --> 02:27:24,080
>> AGE ASSOCIATED, THE FACT OLD

3950
02:27:24,080 --> 02:27:26,400
LUNGS DONE AND YOUNG -- I HAVE

3951
02:27:26,400 --> 02:27:26,840
NEVER HEARD THAT.

3952
02:27:26,840 --> 02:27:29,040
>> IN SOME PATHOLOGY YOU WILL

3953
02:27:29,040 --> 02:27:31,640
FIND NOT MUCH IN ADULT AND IN

3954
02:27:31,640 --> 02:27:33,760
ADULT MOUSE LUNG TOO.

3955
02:27:33,760 --> 02:27:34,560
>> THANKS.

3956
02:27:34,560 --> 02:27:39,680
LET'S GO TO OUR LAST SPEAKER,

3957
02:27:39,680 --> 02:27:45,320
BALI PULENDRAN, TALK ADJUVANT

3958
02:27:45,320 --> 02:27:46,040
AND PREDICTIONS.

3959
02:27:46,040 --> 02:27:49,200
>> THANK YOU SO MUCH, RAFI.

3960
02:27:49,200 --> 02:27:49,680
THANKS, EVERYONE.

3961
02:27:49,680 --> 02:27:51,640
FOR INVITING ME TO THIS VERY

3962
02:27:51,640 --> 02:27:54,000
INTERESTING WORK SYMPOSIUM.

3963
02:27:54,000 --> 02:27:55,520
AND SO LET ME SEE.

3964
02:27:55,520 --> 02:27:57,200
SO I WOULD LIKE TO TELL YOU

3965
02:27:57,200 --> 02:27:58,640
ABOUT RECENT WORK WITH

3966
02:27:58,640 --> 02:28:00,320
ADJUVANTS, THESE ARE MY INDUSTRY

3967
02:28:00,320 --> 02:28:02,040
INTERACTION DISCLOSURES.

3968
02:28:02,040 --> 02:28:04,240
AS YOU HEARD FROM SHANE AND

3969
02:28:04,240 --> 02:28:05,400
MARION AND OTHERS, IT IS NOW

3970
02:28:05,400 --> 02:28:08,120
CLEAR THAT THE mRNA VACCINES

3971
02:28:08,120 --> 02:28:12,240
DEVELOPED BY PFIZER THOUGH

3972
02:28:12,240 --> 02:28:13,200
INDUCING EXCELLENT ANTIBODY

3973
02:28:13,200 --> 02:28:15,880
RESPONSES IN TMB CELL RESPONSES,

3974
02:28:15,880 --> 02:28:17,400
THE DURABILITY OF THE ANTIBODY

3975
02:28:17,400 --> 02:28:20,120
RESPONSES IS REALLY NOT VERY

3976
02:28:20,120 --> 02:28:21,120
HIGH.

3977
02:28:21,120 --> 02:28:22,480
WE HAVE ALSO GOT SIMILAR DATA

3978
02:28:22,480 --> 02:28:24,800
THIS IS A STUDY WE DID AT

3979
02:28:24,800 --> 02:28:25,680
STANFORD WHERE WE CAN SEE THE

3980
02:28:25,680 --> 02:28:27,240
BINDING OF THE NEUTRALIZING

3981
02:28:27,240 --> 02:28:30,360
ANTIBODY TITERS THE HALF LIFE IS

3982
02:28:30,360 --> 02:28:33,840
ABOUT 56 DAYS OR SO.

3983
02:28:33,840 --> 02:28:35,600
THERE ARE EXAMPLES OF LIGHT

3984
02:28:35,600 --> 02:28:38,360
VIRAL VACCINE SUCH AS SMALLPOX

3985
02:28:38,360 --> 02:28:40,560
YELLOW FEVER, MEASLES SO ON THAT

3986
02:28:40,560 --> 02:28:41,840
INDUCE DURABLE ANTIBODY

3987
02:28:41,840 --> 02:28:42,240
RESPONSES.

3988
02:28:42,240 --> 02:28:46,480
SO SEVERAL YEARS AGO WE WERE

3989
02:28:46,480 --> 02:28:50,560
INTERESTED IN WHY, WHAT ARE THE

3990
02:28:50,560 --> 02:28:52,160
MECHANISMS LIKE YELLOW FEVER

3991
02:28:52,160 --> 02:28:53,160
VACCINE INDUCE DO YOU RECALLABLE

3992
02:28:53,160 --> 02:28:53,520
RESPONSE.

3993
02:28:53,520 --> 02:28:55,760
AND IN SOME EXPERIMENTS IN MICE

3994
02:28:55,760 --> 02:29:00,240
WHAT WE SAW IS IMMUNIZATION OF

3995
02:29:00,240 --> 02:29:02,840
MITI 88 KNOCKOUT MICE WITH THE D

3996
02:29:02,840 --> 02:29:04,840
VACCINE RESULTED IN DRAMATICALLY

3997
02:29:04,840 --> 02:29:05,920
DIMINISHED ANTIBODY RESPONSES,

3998
02:29:05,920 --> 02:29:08,320
AND ALSO THE DURABILITY WAS NOT

3999
02:29:08,320 --> 02:29:11,320
VERY HIGH.

4000
02:29:11,320 --> 02:29:12,440
FURTHER WE SHOWED THIS WAS

4001
02:29:12,440 --> 02:29:14,360
THROUGH ACTING THROUGH SEVERAL

4002
02:29:14,360 --> 02:29:17,840
DIFFERENT TLRs SHOWN HERE, TLR

4003
02:29:17,840 --> 02:29:20,000
2, 7, 9 SO THIS LED TO THE IDEA

4004
02:29:20,000 --> 02:29:21,760
THAT A LIVE VIRAL VACCINE SUCH

4005
02:29:21,760 --> 02:29:23,960
AS YELLOW FEVER VACCINE WAS

4006
02:29:23,960 --> 02:29:26,360
INDUCING ITS IMMUNE RESPONSES

4007
02:29:26,360 --> 02:29:28,200
LARGELY BY ACTIVATING MULTIPLE

4008
02:29:28,200 --> 02:29:30,440
DIFFERENT TLRs.

4009
02:29:30,440 --> 02:29:31,880
SO TO ADDRESS THIS ISSUE WE

4010
02:29:31,880 --> 02:29:33,040
ASKED THE QUESTION IS IT

4011
02:29:33,040 --> 02:29:35,720
POSSIBLE TO MAKE A SYNTHETIC

4012
02:29:35,720 --> 02:29:37,360
VIRUS LIKE PARTICLE THAT WOULD

4013
02:29:37,360 --> 02:29:39,360
CONTAIN THE APPROPRIATE TLR OR

4014
02:29:39,360 --> 02:29:40,680
COMBINATION OF APPROPRIATE

4015
02:29:40,680 --> 02:29:42,640
TLRs, THAT WOULD ALLOW TO

4016
02:29:42,640 --> 02:29:45,160
INDUCE DURABLE RESPONSES.

4017
02:29:45,160 --> 02:29:46,640
SO IN COLLABORATION WITH

4018
02:29:46,640 --> 02:29:47,640
(INAUDIBLE) COLLEAGUES AT

4019
02:29:47,640 --> 02:29:49,800
GEORGIA TECH WE DEVELOPED THIS

4020
02:29:49,800 --> 02:29:51,880
POLYLACTIC GLYCOLLIC ACID

4021
02:29:51,880 --> 02:29:53,880
NANOPARTICLES THAT WERE ABOUT

4022
02:29:53,880 --> 02:29:56,360
300 NANOMETERS IN DIAMETER AND

4023
02:29:56,360 --> 02:29:58,520
THAT WE TESTED COMBINATIONS OF

4024
02:29:58,520 --> 02:30:01,080
TLR LIGANDS TO BE ENCAPSULATED

4025
02:30:01,080 --> 02:30:01,920
WITHIN PARTICLES TOGETHER WITH

4026
02:30:01,920 --> 02:30:05,400
ANTIGEN.

4027
02:30:05,400 --> 02:30:07,240
THESE GLEE COTTIC ACID PARTICLES

4028
02:30:07,240 --> 02:30:08,800
RELEASED THEIR CARGO WITH --

4029
02:30:08,800 --> 02:30:11,080
THEY TAKE A FEW DAY DAYS SO WE
CALL

4030
02:30:11,080 --> 02:30:13,000
THIS A SLOW RELEASE DELIVERY

4031
02:30:13,000 --> 02:30:14,720
SYSTEM.

4032
02:30:14,720 --> 02:30:16,920
AND SO (INAUDIBLE) WHO WAS IN MY

4033
02:30:16,920 --> 02:30:19,480
LAB NOW INDEPENDENT AT EMORY

4034
02:30:19,480 --> 02:30:20,440
DATE EMPERIMENTS WITH MICE IN

4035
02:30:20,440 --> 02:30:21,560
THESE PARTICLES AND SHOWED IN

4036
02:30:21,560 --> 02:30:23,040
FACT IF YOU GIVE THE RIGHT

4037
02:30:23,040 --> 02:30:25,120
COMBINATION OF TLR GUY LANDS YOU

4038
02:30:25,120 --> 02:30:27,040
INDUCE A DURABLE GERMINAL CENTER

4039
02:30:27,040 --> 02:30:28,920
RESPONSE AND DURABLE PLASMA CELL

4040
02:30:28,920 --> 02:30:29,480
RESPONSES.

4041
02:30:29,480 --> 02:30:34,840
AND YOU CAN SEE HERE POLYLACTIC

4042
02:30:34,840 --> 02:30:37,080
GLYCOLLIC AID SID CONTAINS

4043
02:30:37,080 --> 02:30:40,920
ALBUMIN, ANOTHER CONTAINS MPL RA

4044
02:30:40,920 --> 02:30:43,480
37, A TLR 7 LIGAND, DURABLE

4045
02:30:43,480 --> 02:30:45,600
RESPONSE SO THIS GAVE US A CLUE

4046
02:30:45,600 --> 02:30:47,840
TO THE RIGHT YOU NEED BUTTONS,

4047
02:30:47,840 --> 02:30:49,800
PLAY SIGNIFICANT ROLE IN THE

4048
02:30:49,800 --> 02:30:51,920
DURABILITY OF ANTIBODY

4049
02:30:51,920 --> 02:30:52,440
RESPONSES.

4050
02:30:52,440 --> 02:30:54,400
BUT THIS WAS IN MICE AND IT IS

4051
02:30:54,400 --> 02:30:57,040
EASY TO DEVELOP LONG LIVE

4052
02:30:57,040 --> 02:30:58,120
RESPONSES IN MICE SO THE

4053
02:30:58,120 --> 02:31:00,840
QUESTION DOES THIS APPLY IN HIGH

4054
02:31:00,840 --> 02:31:04,240
ANIMAL MODEL SUCH AS MONKEYS SO

4055
02:31:04,240 --> 02:31:10,280
TOGETHER WITH FUNDING FROM THE

4056
02:31:10,280 --> 02:31:12,440
GATES FOUNDATION IS ASK WHETHER

4057
02:31:12,440 --> 02:31:14,760
TLR LIGANDS INDUCE LONG LIVE

4058
02:31:14,760 --> 02:31:16,240
ANTIBODY RESPONSES IN RHESUS

4059
02:31:16,240 --> 02:31:19,560
MACAQUES AND THE ANTIGEN IS HIV

4060
02:31:19,560 --> 02:31:20,640
ENVELOPE ANTIGEN YOU CAN SEE

4061
02:31:20,640 --> 02:31:22,840
HERE THE TL 1 NEUTRALIZING

4062
02:31:22,840 --> 02:31:25,120
ANTIBODY RESPONSES, ON THE RIGHT

4063
02:31:25,120 --> 02:31:26,440
PANEL AND WHAT YOU CAN SEE AND

4064
02:31:26,440 --> 02:31:28,640
WE TESTED A NUMBER OF DIFFERENT

4065
02:31:28,640 --> 02:31:30,520
ADJUVANTS SHOWN IN THE DIFFERENT

4066
02:31:30,520 --> 02:31:32,520
COLORS YOU CAN SEE ALLEN IN

4067
02:31:32,520 --> 02:31:34,840
BLACK GLA IN BLUE, NOT STRONG

4068
02:31:34,840 --> 02:31:38,800
RESPONSES, HOWEVER, TLR 78

4069
02:31:38,800 --> 02:31:39,680
LIGANDS INDIVIDUALLY BY

4070
02:31:39,680 --> 02:31:40,840
THEMSELVES OR IN COMBINATION

4071
02:31:40,840 --> 02:31:45,640
WITH THE TLR SUCH AS GLA, OR MPL

4072
02:31:45,640 --> 02:31:47,360
REALLY INDUCE VERY HIGH

4073
02:31:47,360 --> 02:31:50,880
MAGNITUDE AND DURABLE RESPONSES.

4074
02:31:50,880 --> 02:31:52,480
TOGETHER WITH RAFI'S LAB, WHAT

4075
02:31:52,480 --> 02:31:54,800
WE DID WAS TO LOOK AT THE BONE

4076
02:31:54,800 --> 02:31:57,640
MARROW IN THESE MONKEYS AND ASK

4077
02:31:57,640 --> 02:31:59,640
WHAT IS THE FREQUENCY OF LONG

4078
02:31:59,640 --> 02:32:02,000
LIVED BONE MARROW PLASMA CELLS

4079
02:32:02,000 --> 02:32:03,600
AND OBESE ON THE X AXIS

4080
02:32:03,600 --> 02:32:05,520
FOLLOWING THESE MONKEYS FOR MORE

4081
02:32:05,520 --> 02:32:07,840
THAN A YEAR AFTER VACCINATION

4082
02:32:07,840 --> 02:32:10,080
CLEARLY YOU CAN SEE THAT THE

4083
02:32:10,080 --> 02:32:11,720
ADJUVANT SIGNAL PLAY AS MAJOR

4084
02:32:11,720 --> 02:32:14,800
ROLE IN THE FREQUENCY AND THE

4085
02:32:14,800 --> 02:32:16,600
MAINTENANCE OF THESE LONG LIVED

4086
02:32:16,600 --> 02:32:19,120
BONE MARROW PLASMA CELLS, IN

4087
02:32:19,120 --> 02:32:24,160
PARTICULAR THIS 3M 052 SYNTHETIC

4088
02:32:24,160 --> 02:32:26,960
TLR 78 LIGAND OR COMBINATION OF

4089
02:32:26,960 --> 02:32:29,880
GLA PLUS -- TLR -- HIGH

4090
02:32:29,880 --> 02:32:31,360
MAGNITUDE OF BONE MARROW PLASMA

4091
02:32:31,360 --> 02:32:31,880
CELLS.

4092
02:32:31,880 --> 02:32:33,440
THESE ARE ANTIGEN SPECIFIC BONE

4093
02:32:33,440 --> 02:32:37,320
MARROW PLASMA CELLS.

4094
02:32:37,320 --> 02:32:39,040
WHAT HAPPENED IN THE LAST TWO

4095
02:32:39,040 --> 02:32:42,160
YEARS IS WE APPLIED THIS

4096
02:32:42,160 --> 02:32:44,280
KNOWLEDGE TO ASKING CAN WE

4097
02:32:44,280 --> 02:32:45,280
ADJUVANT COVID VACCINE TO

4098
02:32:45,280 --> 02:32:46,440
ENDEUCE DURABLE RESPONSE AND

4099
02:32:46,440 --> 02:32:47,240
THAT IS A WHAT I WOULD LIKE TO

4100
02:32:47,240 --> 02:32:47,760
SHOW YOU.

4101
02:32:47,760 --> 02:32:49,840
SOME OF THIS IS PUBLISHED AND

4102
02:32:49,840 --> 02:32:50,840
OTHER IS WRITING THIS UP.

4103
02:32:50,840 --> 02:32:53,920
SO IN A STUDY THAT WE DID IN

4104
02:32:53,920 --> 02:32:56,040
COLLABORATION WITH NEIL KING AND

4105
02:32:56,040 --> 02:32:56,720
DAVID AT UNIVERSITY OF

4106
02:32:56,720 --> 02:32:59,440
WASHINGTON AND THIS WAS LED BY

4107
02:32:59,440 --> 02:33:01,120
(INAUDIBLE) IN MY LAB WE

4108
02:33:01,120 --> 02:33:02,560
PUBLISHED FEW MONTHS AGO, LAST

4109
02:33:02,560 --> 02:33:07,000
YEAR IN NATURE, WHAT WE DID WAS

4110
02:33:07,000 --> 02:33:08,120
TO USE THIS SUB UNIT VACCINE

4111
02:33:08,120 --> 02:33:09,320
THAT HAD BEEN DEVELOPED BY NEIL

4112
02:33:09,320 --> 02:33:11,640
WHICH IS A RECEPTOR BINDING

4113
02:33:11,640 --> 02:33:14,440
DOMAIN SARS COV-2 EXPRESS ON

4114
02:33:14,440 --> 02:33:16,240
NANOPARTICLE, WE ADJUVANTED THIS

4115
02:33:16,240 --> 02:33:20,440
WITH A VARIETY OF ADJUVANT, CPG

4116
02:33:20,440 --> 02:33:26,040
DNA ASO 3 BASED ADJUVANT FROM

4117
02:33:26,040 --> 02:33:28,920
GLAXOSMITHKLINE SWE ANOTHER

4118
02:33:28,920 --> 02:33:32,440
BASED ADJUVANT, AS 37 A TLR 7

4119
02:33:32,440 --> 02:33:34,320
LIGAND AND ALSO MADE BY

4120
02:33:34,320 --> 02:33:36,280
GLAXOSMITHKLINE AND ALLEN, AND

4121
02:33:36,280 --> 02:33:37,640
THIS DATA WAS PUBLISHED AS YOU

4122
02:33:37,640 --> 02:33:40,320
MIGHT EXPECT WE SAW TERRIFIC

4123
02:33:40,320 --> 02:33:41,520
NEUTRALIZING ANTIBODY RESPONSES,

4124
02:33:41,520 --> 02:33:45,480
WE CHALLENGE THESE MONKEYS AFTER

4125
02:33:45,480 --> 02:33:46,000
UNMOUNTS AFTER SECOND

4126
02:33:46,000 --> 02:33:47,360
IMMUNIZATION AND PROTECTION WAS

4127
02:33:47,360 --> 02:33:49,520
JUST FANTASTIC AND MANY, MANY

4128
02:33:49,520 --> 02:33:50,800
OTHERS REPORTS HAVE COME OUT

4129
02:33:50,800 --> 02:33:51,840
WITH OTHER KINDS OF VACCINE

4130
02:33:51,840 --> 02:33:53,760
SHOWING THAT IT IS FAIRLY EASY

4131
02:33:53,760 --> 02:33:55,360
TO GET GOOD NEUTRALIZING

4132
02:33:55,360 --> 02:33:57,880
ANTIBODY RESPONSES AGAINST

4133
02:33:57,880 --> 02:33:58,440
HOMOLOGOUS STRAIN.

4134
02:33:58,440 --> 02:34:00,360
WHAT I WANT TO SHOW YOU IS TO

4135
02:34:00,360 --> 02:34:01,400
FOLLOW-UP WITH THESE MONKEYS

4136
02:34:01,400 --> 02:34:02,440
SOME OF THESE WERE NOT

4137
02:34:02,440 --> 02:34:02,840
CHALLENGED.

4138
02:34:02,840 --> 02:34:05,280
SO WE WERE ABLE TO LOOK AT THE

4139
02:34:05,280 --> 02:34:07,680
DURABILITY OF THE RESPONSES AND

4140
02:34:07,680 --> 02:34:10,840
USED BY ADJUVANTS SO LET ME SHOW

4141
02:34:10,840 --> 02:34:15,040
YOU HERE, THESE ARE FIVE MONKEYS

4142
02:34:15,040 --> 02:34:18,160
IMMUNIZED DAY O DAY 21, WE

4143
02:34:18,160 --> 02:34:20,080
FOLLOW NEUTRALIZING ANTIBODY

4144
02:34:20,080 --> 02:34:21,080
RESPONSE UP TO SIX MONTHS NOW

4145
02:34:21,080 --> 02:34:23,360
MORE THAN A YEAR, I WILL SHOW

4146
02:34:23,360 --> 02:34:24,000
YOU THAT DATABASEICALLY YOU CAN

4147
02:34:24,000 --> 02:34:27,840
SEE AT THE PEAK VERY NICE TITER

4148
02:34:27,840 --> 02:34:29,280
NEUTRALIZING ANTIBODY RESPONSE,

4149
02:34:29,280 --> 02:34:31,240
ABOUT SEVEN FOLD DROP OVER SIX

4150
02:34:31,240 --> 02:34:31,800
MONTH PERIOD.

4151
02:34:31,800 --> 02:34:33,280
MORE OR LESS SIMILAR TO WHAT

4152
02:34:33,280 --> 02:34:36,240
PEOPLE HAVE SEEN WITH OTHER

4153
02:34:36,240 --> 02:34:37,720
VACCINE PLATFORMS.

4154
02:34:37,720 --> 02:34:40,840
WHAT'S HAPPENED NOW IS THESE

4155
02:34:40,840 --> 02:34:41,960
MONKEYS THAT WE HAVE BEEN

4156
02:34:41,960 --> 02:34:43,760
FOLLOWING IS MORE THAN A YEAR

4157
02:34:43,760 --> 02:34:46,400
SINCE THEY WERE PREVIOUSLY

4158
02:34:46,400 --> 02:34:48,040
IMMUNIZED AND SO LET'S -- THIS

4159
02:34:48,040 --> 02:34:49,640
IS A BIT COMPLEX SO LET ME TALK

4160
02:34:49,640 --> 02:34:51,720
YOU THROUGH IT, IN BLUE YOU SEE

4161
02:34:51,720 --> 02:34:57,280
RBD WUHAN DAY ZERO, RBD WUHAN

4162
02:34:57,280 --> 02:35:00,560
DAY 21, IMMUNIZED SEVERAL MONTHS

4163
02:35:00,560 --> 02:35:02,480
AGO AND WHAT HAPPENED WAS THAT

4164
02:35:02,480 --> 02:35:04,280
THE BETA CORONA VIRUS STRUCK

4165
02:35:04,280 --> 02:35:06,640
THIS WAS AT A TIME WHEN THE B 13

4166
02:35:06,640 --> 02:35:08,760
FIVE LINEAGE WAS EMERGING AND WE

4167
02:35:08,760 --> 02:35:10,000
THOUGHT WE HAVE WE HAVE HAD

4168
02:35:10,000 --> 02:35:11,800
MONKEYS FOR SO LONG, WHY NOT

4169
02:35:11,800 --> 02:35:14,040
BOOST WITH THE RBD NANOPARTICLE

4170
02:35:14,040 --> 02:35:17,280
WITH ASO 3 CONTAINING THE RBD

4171
02:35:17,280 --> 02:35:19,280
BETA FROM THE BETA CORONA VIRUS

4172
02:35:19,280 --> 02:35:20,360
WHICH IS WHAT WE DID HERE.

4173
02:35:20,360 --> 02:35:22,440
SO THIS IS AFTER A PROLONGED

4174
02:35:22,440 --> 02:35:24,640
INTERVAL OF SIX OR SEVEN MONTHS

4175
02:35:24,640 --> 02:35:26,520
THESE WERE BOOSTED WITH THE RBD

4176
02:35:26,520 --> 02:35:28,040
BETA WITH ASO 3.

4177
02:35:28,040 --> 02:35:30,440
WE ALSO HAD ANOTHER GROUP OF

4178
02:35:30,440 --> 02:35:31,640
MONKEYS THAT HAS BEEN IMMUNIZED

4179
02:35:31,640 --> 02:35:35,680
WITH HEKOPRO THE WHOLE SOLUBLE

4180
02:35:35,680 --> 02:35:38,560
ON NANOPARTICLE PREVIOUSLY DAY

4181
02:35:38,560 --> 02:35:40,800
ZERO DAY 21, SIX MONTH GAP THEN

4182
02:35:40,800 --> 02:35:44,240
BOOSTED THEM WITH THE RBD

4183
02:35:44,240 --> 02:35:44,840
NANOPARTICLE.

4184
02:35:44,840 --> 02:35:46,480
THEN WE HAD A CONTROL GROUP OF

4185
02:35:46,480 --> 02:35:48,160
MONKEYS IN WHICH WE IMMUNIZE

4186
02:35:48,160 --> 02:35:52,440
WITH RBD WUHAN NANOPARTICLE RBD

4187
02:35:52,440 --> 02:35:54,440
WUHAN NANOPARTICLE DAY 21, SIX

4188
02:35:54,440 --> 02:35:57,160
MONTH REST THEN RBD WUHAN BOOST

4189
02:35:57,160 --> 02:36:02,680
AS CONTROL FOR THESE TWO GROUPS.

4190
02:36:02,680 --> 02:36:05,560
WE FOLLOWED THE MONKEYS ANOTHER

4191
02:36:05,560 --> 02:36:06,240
SIX OR SERVE MONTHS AFTER FINAL

4192
02:36:06,240 --> 02:36:06,720
THIRD IMMUNIZATION.

4193
02:36:06,720 --> 02:36:08,240
WE ASKED THE QUESTION, WHAT IS

4194
02:36:08,240 --> 02:36:12,480
THE DURABILITY LIKE, HOW ARE

4195
02:36:12,480 --> 02:36:13,720
TITERS AGAINST OMICRON AND WHAT

4196
02:36:13,720 --> 02:36:15,440
IS PROTECTION AFTER OMICRON

4197
02:36:15,440 --> 02:36:18,040
AFTER A LONG WAIT OF SIX OR

4198
02:36:18,040 --> 02:36:18,640
SEVEN MONTHS.

4199
02:36:18,640 --> 02:36:19,840
NOW LET ME SHOW YOU THE DATA.

4200
02:36:19,840 --> 02:36:21,080
FIRST LET'S ASK THE QUESTION

4201
02:36:21,080 --> 02:36:22,760
WHAT HAPPENS IF YOU IMMUNIZE

4202
02:36:22,760 --> 02:36:25,240
MONKEYS AT DAY ZERO WITH RBD

4203
02:36:25,240 --> 02:36:28,840
WUHAN ASO 3, BOOST DAY 21 WITH

4204
02:36:28,840 --> 02:36:30,920
RBD 1 ASO 3 WHAT IS THE

4205
02:36:30,920 --> 02:36:32,520
NEUTRALIZING ANTIBODY TITERS

4206
02:36:32,520 --> 02:36:34,120
AGAINST WUHAN STREAM?

4207
02:36:34,120 --> 02:36:36,160
SO THERE YOU GO YOU HAVE SEEN IN

4208
02:36:36,160 --> 02:36:39,000
IN MANY, MANY PUBLICATIONS

4209
02:36:39,000 --> 02:36:39,560
PREVIOUSLY.

4210
02:36:39,560 --> 02:36:42,240
WE HAVE A VERY GOOD RESPONSE AND

4211
02:36:42,240 --> 02:36:44,560
THEN GRADUAL DECAY, ABOUT SEVEN

4212
02:36:44,560 --> 02:36:45,360
FOLD DROP.

4213
02:36:45,360 --> 02:36:46,680
WHAT ABOUT OMICRON TITERS?

4214
02:36:46,680 --> 02:36:48,120
IT IS HARDLY ANYTHING AS YOU

4215
02:36:48,120 --> 02:36:49,880
HAVE SEEN WITH THE PFIZER AND

4216
02:36:49,880 --> 02:36:51,040
MODERNA VACCINE THERE IS REALLY

4217
02:36:51,040 --> 02:36:52,960
A DRAMATIC HIT WHEN IT COMES TO

4218
02:36:52,960 --> 02:36:53,280
OMICRON.

4219
02:36:53,280 --> 02:36:55,640
NOW LET'S ASK THE QUESTION, WHAT

4220
02:36:55,640 --> 02:36:56,960
ABOUT IN THESE OTHER GROUPS THE

4221
02:36:56,960 --> 02:36:59,840
BLUE GROUP AND RED GROUP,

4222
02:36:59,840 --> 02:37:01,680
MONKEYS THAT HAD BEEN PREVIOUSRY

4223
02:37:01,680 --> 02:37:03,240
IMMUNIZED LONG TIME AGO TWICE

4224
02:37:03,240 --> 02:37:05,760
NOW AFTER SIX MONTHS BOOST,

4225
02:37:05,760 --> 02:37:09,040
BOOST WITH RBD BETA AND WE

4226
02:37:09,040 --> 02:37:09,960
WAITED ANOTHER SIX MONTHS.

4227
02:37:09,960 --> 02:37:10,840
HERE IS THE DATA.

4228
02:37:10,840 --> 02:37:13,400
SO IF YOU LOOK AT THE

4229
02:37:13,400 --> 02:37:14,600
NEUTRALIZING ANTIBODIES AGAINST

4230
02:37:14,600 --> 02:37:16,680
THE WUHAN STRAIN CLEARLY WITH

4231
02:37:16,680 --> 02:37:19,400
THE RBD BETA BOOST YOU SEE THIS

4232
02:37:19,400 --> 02:37:23,240
TREMENDOUS BOOST, IT GOES FROM

4233
02:37:23,240 --> 02:37:24,800
ABOUT YOU TO ABOUT 60 TO 70,000,

4234
02:37:24,800 --> 02:37:28,040
THAT IS A PRETTY DRAY DRAMATIC

4235
02:37:28,040 --> 02:37:28,360
BOOST.

4236
02:37:28,360 --> 02:37:30,960
IF YOU WAIT ANOTHER 130 TO 160

4237
02:37:30,960 --> 02:37:32,840
DAYS THERE IS A GRADUAL DECLINE,

4238
02:37:32,840 --> 02:37:34,040
THE TITLERS ARE STILL REALLY

4239
02:37:34,040 --> 02:37:35,640
QUITE HIGH.

4240
02:37:35,640 --> 02:37:37,880
IF YOU LOOK WHAT ABOUT THE

4241
02:37:37,880 --> 02:37:38,360
OMICRON?

4242
02:37:38,360 --> 02:37:41,600
YOU SEE THESE MONKEYS HAVE THE

4243
02:37:41,600 --> 02:37:42,560
CORRESPONDING TIME POINTS HAVE

4244
02:37:42,560 --> 02:37:46,240
REALLY QUITE A HIGH OMICRON

4245
02:37:46,240 --> 02:37:48,840
TITER HERE AND EVEN AT 130 TO

4246
02:37:48,840 --> 02:37:50,120
160 DAYS THE TITLERS SEEM TO BE

4247
02:37:50,120 --> 02:37:52,440
FAIRLY HIGH.

4248
02:37:52,440 --> 02:37:54,040
THIS IS WHAT YOU SEE AGAINST

4249
02:37:54,040 --> 02:37:56,440
BETA STREAM SO REALLY BY HIGH

4250
02:37:56,440 --> 02:37:57,120
TITERS.

4251
02:37:57,120 --> 02:37:59,200
I DO WANT TO EMPHASIZE THIS

4252
02:37:59,200 --> 02:38:03,640
POINT, I WANT TO SHOW YOU THE

4253
02:38:03,640 --> 02:38:04,240
PSEUDOVIRUS NEUTRALIZING

4254
02:38:04,240 --> 02:38:08,440
ANTIBODY AFTER THE THIRD 21 DAYS

4255
02:38:08,440 --> 02:38:09,600
AFTER THIRD IMMUNIZATION IN GRAY

4256
02:38:09,600 --> 02:38:11,440
IS TITERS THAT YOU SEE AGAINST

4257
02:38:11,440 --> 02:38:14,280
THE ANCESTRAL STRAIN.

4258
02:38:14,280 --> 02:38:15,640
MANY P RED AGAINST OMICRON

4259
02:38:15,640 --> 02:38:19,160
STRAIN SO THERE IS FOUR THE FIVE

4260
02:38:19,160 --> 02:38:20,440
FOLD HIT AFTER THIRD

4261
02:38:20,440 --> 02:38:21,040
IMMUNIZATION.

4262
02:38:21,040 --> 02:38:23,240
WHAT ABOUT 130 TO 160 DAYS AFTER

4263
02:38:23,240 --> 02:38:24,280
THE THIRD IMMUNIZATION?

4264
02:38:24,280 --> 02:38:25,520
AGAIN THE TITLERS AS YOU SAW IN

4265
02:38:25,520 --> 02:38:28,320
THE PREVIOUS SLIDE ARE HIGH IN

4266
02:38:28,320 --> 02:38:31,200
THE MONKEYS THAT WERE BLUESST

4267
02:38:31,200 --> 02:38:32,560
BOOST WITH THE RBD BETA BUT

4268
02:38:32,560 --> 02:38:35,080
THERE IS A HIT, ABOUT SIX FOLD

4269
02:38:35,080 --> 02:38:39,160
WHEN YOU LOOK AT OMICRON.

4270
02:38:39,160 --> 02:38:40,240
HOW DOES THIS COMPARE WITH WHAT

4271
02:38:40,240 --> 02:38:42,000
IS REPORTED IN LITERATURE IN

4272
02:38:42,000 --> 02:38:42,800
HUMANS WITH PFIZER?

4273
02:38:42,800 --> 02:38:47,240
THIS IS A STUDY WITH (INAUDIBLE)

4274
02:38:47,240 --> 02:38:48,800
PUBLISHED LAST WEEK IN SCIENCE

4275
02:38:48,800 --> 02:38:52,240
TRANSLATIONAL MEDICINE AND YOU

4276
02:38:52,240 --> 02:38:53,640
CAN SEE USING THE SAME ASSAY,

4277
02:38:53,640 --> 02:38:55,560
THESE WERE DONE IN (INAUDIBLE)

4278
02:38:55,560 --> 02:38:57,320
LAB THOUGH HUGE CAVEAT IS THAT

4279
02:38:57,320 --> 02:38:59,840
OUR STUDY IS IN MONKEYS THE

4280
02:38:59,840 --> 02:39:01,440
STUDY PUBLISHED ON IS IN HUMAN

4281
02:39:01,440 --> 02:39:03,120
SO YOU HAVE THE TAKE THIS WITH A

4282
02:39:03,120 --> 02:39:06,640
PINCH OF SALT BUT WHATEVER IT IS

4283
02:39:06,640 --> 02:39:08,040
WORTH YOU CAN SEE IF YOU BOOST

4284
02:39:08,040 --> 02:39:12,360
WITH PFIZER VACCINE, THIS IS A

4285
02:39:12,360 --> 02:39:13,920
THIRD IMMUNIZATION AT PEAK OF

4286
02:39:13,920 --> 02:39:15,040
THAT RESPONSE YOU SEE THE

4287
02:39:15,040 --> 02:39:17,960
ANCESTRAL TITERS ABOUT THE

4288
02:39:17,960 --> 02:39:20,440
MEDIAN ABOUT 13,000 BUT YOU TAKE

4289
02:39:20,440 --> 02:39:22,000
A DRAMATIC HIT WITH OMICRON.

4290
02:39:22,000 --> 02:39:23,480
SO YOU CAN COMPARE THESE ONE IS

4291
02:39:23,480 --> 02:39:25,040
IN HUMAN, THE OTHER IN MONKEYS

4292
02:39:25,040 --> 02:39:27,640
BUT FOR WHAT IT IS WORTH, THE

4293
02:39:27,640 --> 02:39:28,520
ADJUVANT PROGRAM SEEMS TO BE

4294
02:39:28,520 --> 02:39:31,640
HAVING LESS OF IMPACT ON THE HIT

4295
02:39:31,640 --> 02:39:35,240
THAT YOU HAVE WITH OMICRON.

4296
02:39:35,240 --> 02:39:37,160
THE LAST COUPLE OF SLIDES, WHAT

4297
02:39:37,160 --> 02:39:41,120
ABOUT THIS ISSUE OF DURABILITY

4298
02:39:41,120 --> 02:39:43,520
AFTER THE SECOND VERSUS THIRD

4299
02:39:43,520 --> 02:39:44,080
IMMUNIZATION.

4300
02:39:44,080 --> 02:39:45,160
SHANE REFERRED TO THIS BUT I CAN

4301
02:39:45,160 --> 02:39:48,320
SPEAK FROM OUR DATA.

4302
02:39:48,320 --> 02:39:51,800
SO LET ME ALLOW YOU TO FOCUS ON

4303
02:39:51,800 --> 02:39:52,760
THE PANEL ON THE RIGHT.

4304
02:39:52,760 --> 02:39:55,040
WHAT ARE WE LOOKING AT THE PANEL

4305
02:39:55,040 --> 02:39:56,440
ON THE RIGHT?

4306
02:39:56,440 --> 02:39:58,400
THE FULL REDUCTION IN THE

4307
02:39:58,400 --> 02:40:01,480
NEUTRALIZING ANTIBODY TITERS, AT

4308
02:40:01,480 --> 02:40:05,040
FIVE TO SIX MONTHS POST TERTIARY

4309
02:40:05,040 --> 02:40:07,440
POST SECONDARY IMMUNIZATION OR

4310
02:40:07,440 --> 02:40:09,560
POST TERTIARY IMMUNIZATION.

4311
02:40:09,560 --> 02:40:11,440
AND RELATIVE TO THE LEVELS AT

4312
02:40:11,440 --> 02:40:13,320
THE PEAK.

4313
02:40:13,320 --> 02:40:16,200
SO YOU SEE WITH THE FIRST STUDY

4314
02:40:16,200 --> 02:40:20,240
WE PUBLISHED WE SAW ABILITY A

4315
02:40:20,240 --> 02:40:22,280
FIVE FOLD DROP OVER FIVE MONTHS

4316
02:40:22,280 --> 02:40:25,840
PERIOD IN THE SECOND STUDY WHICH

4317
02:40:25,840 --> 02:40:29,240
WE ARE NOW DOING WE SEE AGAIN

4318
02:40:29,240 --> 02:40:30,600
ABOUT A FIVE FOLD DROP.

4319
02:40:30,600 --> 02:40:32,400
AFTER THE THIRD IMMUNIZATION IN

4320
02:40:32,400 --> 02:40:35,600
THIS CASE WITH BETA CORONA

4321
02:40:35,600 --> 02:40:37,440
VIRUS, WITH THE BETA STREAM, YOU

4322
02:40:37,440 --> 02:40:39,360
SEE ABOUT A FIVE FOLD DROP SO AT

4323
02:40:39,360 --> 02:40:40,440
LEAST WITH THESE ADJUVANT

4324
02:40:40,440 --> 02:40:45,400
VACCINE WE DON'T SEE IMPROVEMENT

4325
02:40:45,400 --> 02:40:49,560
IN THE DECLINE IN TERMS OF THIRD

4326
02:40:49,560 --> 02:40:49,960
VACCINATION.

4327
02:40:49,960 --> 02:40:51,120
LAST IS CHALLENGE.

4328
02:40:51,120 --> 02:40:52,680
WHAT DO THESE MONKEYS LOOK IF

4329
02:40:52,680 --> 02:40:54,920
YOU CHALLENGE ANYTHING FROM DAY

4330
02:40:54,920 --> 02:40:56,640
130 TO DAY 160 AFTER

4331
02:40:56,640 --> 02:40:57,040
IMMUNIZATION.

4332
02:40:57,040 --> 02:40:58,440
THESE ARE THE RESULTS, THIS IS

4333
02:40:58,440 --> 02:41:00,040
STILL ONGOING IN THE

4334
02:41:00,040 --> 02:41:01,720
UNVACCINATED MONKEYS, FIRST OF

4335
02:41:01,720 --> 02:41:03,960
ALL OMICRON IS A WHIMPY VIRUS BY

4336
02:41:03,960 --> 02:41:05,880
THAT I MEAN HARDLY HAS INFECTION

4337
02:41:05,880 --> 02:41:08,120
IN THE LUNG, YOU DO DETECT VIRUS

4338
02:41:08,120 --> 02:41:10,240
IN THE NASAL TRACKS AND YOU CAN

4339
02:41:10,240 --> 02:41:13,840
SEE IN THE UNVACCINATED MONKEYS

4340
02:41:13,840 --> 02:41:15,600
YOU CAN DETECT VIRUS BUT IN ALL

4341
02:41:15,600 --> 02:41:17,240
VACCINATED MONKEYS WE HAVE SEEN

4342
02:41:17,240 --> 02:41:20,440
SO FAR THESE ARE CHALLENGED 170

4343
02:41:20,440 --> 02:41:21,840
DAYS AFTER THE FINAL

4344
02:41:21,840 --> 02:41:23,040
IMMUNIZATION SO THAT IS ABOUT

4345
02:41:23,040 --> 02:41:24,640
SIX MONTHS WE SEE NOTHING.

4346
02:41:24,640 --> 02:41:26,640
SO THIS VARIES ONGOING IN THE

4347
02:41:26,640 --> 02:41:28,440
NEXT TWO WEEKS HAVE THE COMPLETE

4348
02:41:28,440 --> 02:41:29,920
DATA SET SO I WANT TO SUMMARIZE

4349
02:41:29,920 --> 02:41:30,800
WHAT WE ARE LEARNING.

4350
02:41:30,800 --> 02:41:32,720
I STARTED OFF BY SAYING THAT

4351
02:41:32,720 --> 02:41:35,040
THE mRNA VACCINE DIDN'T REALLY

4352
02:41:35,040 --> 02:41:37,080
INDUCE DURABLE NEUTRALIZING

4353
02:41:37,080 --> 02:41:39,920
ANTIBODY RESPONSE, THEN I

4354
02:41:39,920 --> 02:41:41,600
MENTIONED THE VIRAL VACCINES

4355
02:41:41,600 --> 02:41:44,120
SUCH AS YELLOW FEVER DOES INDUCE

4356
02:41:44,120 --> 02:41:45,640
DURABLE NEUTRALIZING ANTIBODY

4357
02:41:45,640 --> 02:41:47,520
RESPONSE AND WE BELIEVE THIS IS

4358
02:41:47,520 --> 02:41:49,120
PARTLY MEDIATED THROUGH THE

4359
02:41:49,120 --> 02:41:51,160
RIGHT INNATE SIGNALS INCLUDED

4360
02:41:51,160 --> 02:41:54,280
TOLL LIKE RECEPTOR 2, 3, 7, 9, I

4361
02:41:54,280 --> 02:41:56,240
DIDN'T SHOW YOU THE DATA BUT

4362
02:41:56,240 --> 02:41:58,440
TRIGGERS MDFI WE PUBLISHED THAT

4363
02:41:58,440 --> 02:41:59,280
SEVERAL YEARS AGO.

4364
02:41:59,280 --> 02:42:02,040
NOW, WITH THE mRNA VACCINE WE

4365
02:42:02,040 --> 02:42:03,520
LOOKED AT THIS IN MICE, THE

4366
02:42:03,520 --> 02:42:06,120
PFIZER mRNA VACCINE WE LOOK AT

4367
02:42:06,120 --> 02:42:07,920
DIFFERENT KNOCK OUTS AND WE SEE

4368
02:42:07,920 --> 02:42:09,480
THAT THE IMMUNE RESPONSE WHETHER

4369
02:42:09,480 --> 02:42:13,640
B CELL OR T-CELL RESPONSES, TLR

4370
02:42:13,640 --> 02:42:15,280
INDEPENDENT INFLAMMASOME

4371
02:42:15,280 --> 02:42:18,280
INDEPENDENT BUT MDA 5 DEPENDENT.

4372
02:42:18,280 --> 02:42:23,240
AND SO THAT IS NOT IDUCING

4373
02:42:23,240 --> 02:42:23,640
DURABLE RESPONSE.

4374
02:42:23,640 --> 02:42:26,760
WHAT IS THE SIGNAL, ADDITIONAL

4375
02:42:26,760 --> 02:42:28,640
SIGNATURE MALL TO MAKE THIS

4376
02:42:28,640 --> 02:42:29,520
VACCINE LIKE THIS VACCINE.

4377
02:42:29,520 --> 02:42:32,520
FINALLY I GAVE EXAMPLES OF

4378
02:42:32,520 --> 02:42:35,640
PROTEIN ADJUVANTED VACCINE, A

4379
02:42:35,640 --> 02:42:37,720
TLR 78 LIGAND ASO 3 THEY SEEM TO

4380
02:42:37,720 --> 02:42:40,160
BE INDUCING FAIRLY DURABLE

4381
02:42:40,160 --> 02:42:41,720
RESPONSES BUT I PUT A QUESTION

4382
02:42:41,720 --> 02:42:43,440
MARK BECAUSE THE QUESTION IS, IS

4383
02:42:43,440 --> 02:42:45,120
THE HALF LIFE OF THE ANTIBODY

4384
02:42:45,120 --> 02:42:47,200
RESPONSE REALLY AS HIGH AS THE

4385
02:42:47,200 --> 02:42:48,040
LIVE VIRAL VACCINE?

4386
02:42:48,040 --> 02:42:50,120
IF NOT WHAT IS MISSING PICTURE

4387
02:42:50,120 --> 02:42:50,320
HERE?

4388
02:42:50,320 --> 02:42:51,840
SO THAT IS ALL I HAD TO SAY,

4389
02:42:51,840 --> 02:42:53,640
THESE ARE ALL THE GREAT PEOPLE

4390
02:42:53,640 --> 02:42:57,360
WHO DID THE WORK, THE MONKEY

4391
02:42:57,360 --> 02:43:00,040
WORK IS BEING LED BY ABSOLUTELY

4392
02:43:00,040 --> 02:43:02,360
FANTASTIC POST DOC NOW SENIOR

4393
02:43:02,360 --> 02:43:05,960
SCIENTIST IN COLLABORATION WITH

4394
02:43:05,960 --> 02:43:07,040
(INDISCERNIBLE) THIS WAS A

4395
02:43:07,040 --> 02:43:09,400
STRONG COLLABORATION WITH NEIL

4396
02:43:09,400 --> 02:43:11,280
KING AND DAVID AND

4397
02:43:11,280 --> 02:43:12,680
GLAXOSMITHKLINE AND FUNDING FROM

4398
02:43:12,680 --> 02:43:14,520
THE BILL AND MELINDA GATES

4399
02:43:14,520 --> 02:43:15,000
FOUNDATION.

4400
02:43:15,000 --> 02:43:19,360
THANK YOU.

4401
02:43:19,360 --> 02:43:31,040
>> QUESTIONS FOR BALI.

4402
02:43:31,040 --> 02:43:33,880
LET ME ASK A QUESTION.

4403
02:43:33,880 --> 02:43:41,240
SO IN THIS BIT OF A BROADER

4404
02:43:41,240 --> 02:43:42,960
QUESTION FOR DAVID, I WAS GOING

4405
02:43:42,960 --> 02:43:44,640
TO ASK HIM THIS MANY THE

4406
02:43:44,640 --> 02:43:45,240
DISCUSSION.

4407
02:43:45,240 --> 02:43:47,040
SO WHAT -- A LOT OF PEOPLE ARE

4408
02:43:47,040 --> 02:43:53,000
USING RBD FOR POTENTIAL VACCINE.

4409
02:43:53,000 --> 02:43:54,320
AND JUST WANT TO THROW THE

4410
02:43:54,320 --> 02:43:56,160
QUESTION OUT TO DAVID AND TO

4411
02:43:56,160 --> 02:43:56,760
YOU.

4412
02:43:56,760 --> 02:43:59,120
WHAT ARE THE PROS AND CONS OF

4413
02:43:59,120 --> 02:44:02,360
USING RBD AS A VACCINE OPPOSED

4414
02:44:02,360 --> 02:44:03,840
TO (INAUDIBLE)?

4415
02:44:03,840 --> 02:44:05,600
>> DAVID IS CLEARLY THE BEST

4416
02:44:05,600 --> 02:44:06,840
PERSON TO ANSWER THIS BUT I ARE

4417
02:44:06,840 --> 02:44:08,800
GIVE MY TWO CENTS WORTH.

4418
02:44:08,800 --> 02:44:11,040
OF COURSE WE ARE NOT STRUCTURAL

4419
02:44:11,040 --> 02:44:13,840
PEOPLE SO WE ARE COMPLETELY

4420
02:44:13,840 --> 02:44:14,120
AGNOSTIC.

4421
02:44:14,120 --> 02:44:16,720
IF YOU LIST REASONS WHY PROTEOME

4422
02:44:16,720 --> 02:44:18,160
YOU MIGHT IMAGINE A PROTEIN HAS

4423
02:44:18,160 --> 02:44:19,440
MANY DIFFERENT EPITOPES

4424
02:44:19,440 --> 02:44:22,680
INCLUDING T HELPER EPITOPES SO

4425
02:44:22,680 --> 02:44:24,440
OBVIOUSLY ONE MIGHT THINK THAT

4426
02:44:24,440 --> 02:44:26,320
IT IS ADVANTAGEOUS TO USE A

4427
02:44:26,320 --> 02:44:28,120
WHOLE PROTEIN IN TERMS OF

4428
02:44:28,120 --> 02:44:29,720
GETTING PROPER T HELPER CELL

4429
02:44:29,720 --> 02:44:31,040
RESPONSE BUT ALSO MAYBE MORE

4430
02:44:31,040 --> 02:44:32,360
BREADTH THAN OTHER END TERMINAL

4431
02:44:32,360 --> 02:44:37,520
DOMAIN AND RBD.

4432
02:44:37,520 --> 02:44:39,840
IN OUR CASE WE HAVE COMPARED THE

4433
02:44:39,840 --> 02:44:42,680
RBD AND THE HEXAPRO SIDE BY SIDE

4434
02:44:42,680 --> 02:44:43,920
AND IN TERMS OF DURABILITY OR

4435
02:44:43,920 --> 02:44:45,240
MAGNITUDE WE DON'T SEE A

4436
02:44:45,240 --> 02:44:45,840
DIFFERENCE.

4437
02:44:45,840 --> 02:44:46,960
WE ARE LOOKING AT ISSUES OF

4438
02:44:46,960 --> 02:44:48,120
BREADTH BUT NOT TOO MUCH DATA ON

4439
02:44:48,120 --> 02:44:48,600
THAT.

4440
02:44:48,600 --> 02:44:49,960
BUT DAVID SHOULD ANSWER THIS

4441
02:44:49,960 --> 02:44:50,800
QUESTION.

4442
02:44:50,800 --> 02:44:55,240
>> AND SPECIFICALLY SPECIFICALLY

4443
02:44:55,240 --> 02:45:00,040
IN CONTEXT OF OMICRON.

4444
02:45:00,040 --> 02:45:02,640
THAT -- SO MAYBE FROM DAVID THEN

4445
02:45:02,640 --> 02:45:04,000
TO ROSS AND MARK.

4446
02:45:04,000 --> 02:45:06,280
>> SIMPLE ANSWER IS THAT THE RBD

4447
02:45:06,280 --> 02:45:09,440
CAN GIVE YOU VERY, VERY POTENT

4448
02:45:09,440 --> 02:45:10,600
NEUTRALIZING ANTIBODIES.

4449
02:45:10,600 --> 02:45:12,480
BUT WHAT WE ARE MISSING IS ALL

4450
02:45:12,480 --> 02:45:14,560
THESE ASSAYS ARE ONLY LOOK AT

4451
02:45:14,560 --> 02:45:15,760
NEUTRALIZATION, NOT PROTECTION.

4452
02:45:15,760 --> 02:45:17,280
SO WHAT WE DON'T KNOW IS TO WHAT

4453
02:45:17,280 --> 02:45:19,640
EXTENT WE ARE LOSING PROTECTIVE

4454
02:45:19,640 --> 02:45:21,600
ANTIBODIES WHICH ARE AGAINST

4455
02:45:21,600 --> 02:45:23,000
EPITOPES WHICH MIGHT BE MORE

4456
02:45:23,000 --> 02:45:23,600
CONSERVATIVE.

4457
02:45:23,600 --> 02:45:25,000
BUT THAT BEING SAID THERE'S LOTS

4458
02:45:25,000 --> 02:45:27,880
OF GREAT DATA TO SUGGEST THAT

4459
02:45:27,880 --> 02:45:30,840
PROTEIN DELIVERY OF RBD, BECAUSE

4460
02:45:30,840 --> 02:45:33,680
CLEARLY THE MONOMERIC RBD IS

4461
02:45:33,680 --> 02:45:34,440
WORTHLESS ANTIGEN BEEN SHOWN

4462
02:45:34,440 --> 02:45:36,680
BECAUSE IT IS NOT LARGE ENOUGH

4463
02:45:36,680 --> 02:45:39,240
TO BE TRACK PROPERLY IN GERMINAL

4464
02:45:39,240 --> 02:45:40,720
CENTERS NOT ENOUGH GLYCOSYLATION

4465
02:45:40,720 --> 02:45:42,440
TO BE USEFUL BUT CLEARLY AS

4466
02:45:42,440 --> 02:45:44,760
THESE NANOPARTICLES CAN BE VERY

4467
02:45:44,760 --> 02:45:45,960
SUCCESSFUL BUT WHAT WE ARE

4468
02:45:45,960 --> 02:45:47,360
MISSING IS IN VITRO ASSAYS THAT

4469
02:45:47,360 --> 02:45:48,960
WE DO TO MEASURE DURABILITY IS

4470
02:45:48,960 --> 02:45:51,520
ONLY EVALUATING NEUTRALIZATION.

4471
02:45:51,520 --> 02:45:53,240
>> THANKS, DAVID.

4472
02:45:53,240 --> 02:45:54,280
ROSS AND THEN MARK.

4473
02:45:54,280 --> 02:45:55,640
>> THIS IS KIND OF FOR EVERYBODY

4474
02:45:55,640 --> 02:46:00,040
AS WELL BUT FOR YOUR DATA, BALI,

4475
02:46:00,040 --> 02:46:03,280
WE HAVE SEEN IN ANALYZING BOTH

4476
02:46:03,280 --> 02:46:05,480
POST SECOND IMMUNIZATION VERSUS

4477
02:46:05,480 --> 02:46:07,520
POST BOOST, THAT AFTER THE

4478
02:46:07,520 --> 02:46:09,160
SECOND IMMUNIZATION FOR mRNA

4479
02:46:09,160 --> 02:46:11,440
VACCINE IT IS EXPONENTIAL DECAY,

4480
02:46:11,440 --> 02:46:13,640
A GEOMETRIC DECAY, WHEREAS AFTER

4481
02:46:13,640 --> 02:46:16,400
BOOST IT IS LINEAR SO THAT IS

4482
02:46:16,400 --> 02:46:17,240
MATHEMATICALLY THOSE FIT

4483
02:46:17,240 --> 02:46:18,560
INCREDIBLY WELL.

4484
02:46:18,560 --> 02:46:21,040
WE DON'T KNOW IF THAT IS TRUE,

4485
02:46:21,040 --> 02:46:22,600
WE HAVE GOT 30 TO 40 RESPONSES

4486
02:46:22,600 --> 02:46:24,320
TO LOOK AT BUT OTHER PEOPLE GOT

4487
02:46:24,320 --> 02:46:25,720
HUNDREDS AND WONDERING BROADLY

4488
02:46:25,720 --> 02:46:29,240
SPEAKING IS THAT TRUE?

4489
02:46:29,240 --> 02:46:29,840
GREAT QUESTION.

4490
02:46:29,840 --> 02:46:33,680
WE HAVEN'T YET CALCULATED THE EK

4491
02:46:33,680 --> 02:46:35,080
RATES ON MONKEY EXPERIMENTS.

4492
02:46:35,080 --> 02:46:38,960
WE PLAN TO DO THIS WITH VERONICA

4493
02:46:38,960 --> 02:46:40,560
WHOEVER WORKS WITH ROSS AT

4494
02:46:40,560 --> 02:46:42,280
EMORY, SHE A PERSON WHO WORKED

4495
02:46:42,280 --> 02:46:43,320
WITH US ON THE PFIZER VACCINE SO

4496
02:46:43,320 --> 02:46:45,120
WE ARE SENDING SAMPLES AND

4497
02:46:45,120 --> 02:46:46,120
HOPEFULLY THE NEXT MONTH OR SO

4498
02:46:46,120 --> 02:46:48,360
WE WILL HAVE A PROPER DECAY RATE

4499
02:46:48,360 --> 02:46:49,640
CALCULATION FOR MONKEY ADJUVANT.

4500
02:46:49,640 --> 02:46:54,520
WE DON'T HAVE THAT DATA YET.

4501
02:46:54,520 --> 02:46:57,040
>> THERE WAS THESE OLD ASSAYS

4502
02:46:57,040 --> 02:46:58,240
WHERE YOU COULD ADD TROPIC

4503
02:46:58,240 --> 02:47:00,400
AGENTS, AS A WAY TO GET SOME

4504
02:47:00,400 --> 02:47:02,440
SENSE OF LIKE THE AVERAGE

4505
02:47:02,440 --> 02:47:05,720
AFFINITY OF A POPULATION OF

4506
02:47:05,720 --> 02:47:07,400
ANTIBODIES, IS ANYONE TRIED THAT

4507
02:47:07,400 --> 02:47:10,160
WITH THESE KINDS OF -- WITH

4508
02:47:10,160 --> 02:47:12,240
ANTIBODIES IN THE SERUM OF THESE

4509
02:47:12,240 --> 02:47:14,640
PATIENTS OR PEOPLE WHO ARE GET

4510
02:47:14,640 --> 02:47:17,040
VACCINATED TO SEE HOW THE

4511
02:47:17,040 --> 02:47:18,320
AFFINITY OF THE ANTIBODIES ARE

4512
02:47:18,320 --> 02:47:21,160
CHANGING?

4513
02:47:21,160 --> 02:47:22,000
>> GREAT QUESTION.

4514
02:47:22,000 --> 02:47:24,920
WE HAVEN'T BUT I DON'T KNOW.

4515
02:47:24,920 --> 02:47:26,520
>> ARE THERE BETTER WAYS TO DO

4516
02:47:26,520 --> 02:47:27,240
THAT NOW?

4517
02:47:27,240 --> 02:47:28,920
I'M THINKING OF THIS IS STUFF

4518
02:47:28,920 --> 02:47:32,560
FROM PROBABLY THE '80s, BUT I

4519
02:47:32,560 --> 02:47:34,200
GUESS WE COULD JUST HAVE

4520
02:47:34,200 --> 02:47:35,240
MICHELLE SEQUENCE EVERY ANTIBODY

4521
02:47:35,240 --> 02:47:37,720
AND MEASURE AFFINITY BUT I STILL

4522
02:47:37,720 --> 02:47:38,760
THINK THERE COULD BE SOME

4523
02:47:38,760 --> 02:47:42,840
ADVANTAGE TO DOING THIS WITH

4524
02:47:42,840 --> 02:47:43,840
POLYCLONAL SIERRA, BEFORE COVID

4525
02:47:43,840 --> 02:47:45,840
HIT THERE WAS A HUGE DEAL IN THE

4526
02:47:45,840 --> 02:47:48,240
B CELL FIELD WAS HOW GOOD

4527
02:47:48,240 --> 02:47:49,640
SECONDARY GERMINAL CENTERS DID

4528
02:47:49,640 --> 02:47:51,880
THEY HAPPEN, AND WHERE ARE THE

4529
02:47:51,880 --> 02:47:53,720
BOOSTED ANTIBODIES COMING FROM

4530
02:47:53,720 --> 02:47:57,080
AND HOW GOOD ARE THEY?

4531
02:47:57,080 --> 02:47:58,800
>>PROFESSOR:  YEAH.

4532
02:47:58,800 --> 02:48:01,040
>> I WOULD SAY THE STRONGEST

4533
02:48:01,040 --> 02:48:04,000
EVIDENCE COMES FROM SEQUENCE

4534
02:48:04,000 --> 02:48:08,040
MONOCLONALS, WHICH IS THAT

4535
02:48:08,040 --> 02:48:09,200
SHORTLY AFTER INFECTION THEY

4536
02:48:09,200 --> 02:48:12,920
IMPROVE FOR SIX PLUS MONTHS AND

4537
02:48:12,920 --> 02:48:18,720
AFTER VACCINATION CLEARLY PRETTY

4538
02:48:18,720 --> 02:48:20,720
GOOD, OBSERVATION OF

4539
02:48:20,720 --> 02:48:22,600
NEUTRALIZING ANTI-BOY IT IS

4540
02:48:22,600 --> 02:48:24,160
AFTER OMICRON GETTING HIT BE --

4541
02:48:24,160 --> 02:48:27,680
ANTIBODIES OF OMICRON WITH THREE

4542
02:48:27,680 --> 02:48:30,160
ANCESTRAL -- THE MEMORY B CELLS

4543
02:48:30,160 --> 02:48:32,600
AFTER SECOND LINE DID CONTAIN

4544
02:48:32,600 --> 02:48:34,440
MEMORY B CELLS THAT RECOGNIZED

4545
02:48:34,440 --> 02:48:35,920
OMICRON, THOSE THEN COME OUT AT

4546
02:48:35,920 --> 02:48:39,920
THE POLYCLONAL LEVEL NO, PEOPLE

4547
02:48:39,920 --> 02:48:42,920
THAT USE UREA BASED ASSAYS BUT

4548
02:48:42,920 --> 02:48:45,520
PEOPLE DO SOMETIMES GO INSTEAD

4549
02:48:45,520 --> 02:48:47,360
WITH ANALYZES WITH AREA UNDER

4550
02:48:47,360 --> 02:48:49,240
CURVE ANALYSIS INTEGRATING THE

4551
02:48:49,240 --> 02:48:52,040
END POINT TITER AND THE OVERALL

4552
02:48:52,040 --> 02:48:53,840
SHAPE WHICH DOES GIVE YOU A

4553
02:48:53,840 --> 02:48:57,440
COMBO OF AFFINITY AND TOTAL

4554
02:48:57,440 --> 02:48:58,880
QUANTITY AND SHIFT OVER TIME BUT

4555
02:48:58,880 --> 02:49:00,640
IT IS TOUGH TO -- YOU STILL

4556
02:49:00,640 --> 02:49:02,120
CAN'T EXTRACT HOW MUCH IS

4557
02:49:02,120 --> 02:49:04,240
AFFINITY IMPROVING OVER TIME

4558
02:49:04,240 --> 02:49:08,240
VERSUS THE ACTUAL AMOUNT.

4559
02:49:08,240 --> 02:49:15,880
>> ALISON AND DAN.

4560
02:49:15,880 --> 02:49:16,520
WE A OVER TIME.

4561
02:49:16,520 --> 02:49:19,640
>> SO SHOULD WE TAG EVERYONE AND

4562
02:49:19,640 --> 02:49:21,480
CONCLUDE OR DO YOU WANT TO

4563
02:49:21,480 --> 02:49:22,000
CONTINUE?

4564
02:49:22,000 --> 02:49:25,440
>> RAFI, WE HAVE GOTTEN A

4565
02:49:25,440 --> 02:49:26,600
DISPENSATION, YOU CAN GO OVER

4566
02:49:26,600 --> 02:49:29,320
TIME AND WE'LL EXTEND THE

4567
02:49:29,320 --> 02:49:31,360
BROADCAST, THAT'S PROVIDED THE

4568
02:49:31,360 --> 02:49:33,520
COUNCIL MEMBERS CAN STAY PAST 4

4569
02:49:33,520 --> 02:49:36,880
O'CLOCK TO HEAR THE CONCEPT

4570
02:49:36,880 --> 02:49:37,840
CLEARANCE.

4571
02:49:37,840 --> 02:49:39,240
>> MAYBE WE CAN GO -- TEN --

4572
02:49:39,240 --> 02:49:41,600
ANOTHER TEN MINUTES THEN OPEN UP

4573
02:49:41,600 --> 02:49:43,200
TO THE AUDIENCE FOR QUESTIONS.

4574
02:49:43,200 --> 02:49:44,040
>> YEAH.

4575
02:49:44,040 --> 02:49:49,600
GOOD.

4576
02:49:49,600 --> 02:49:50,800
COUNCIL MEMBERS, QUESTIONS FOR

4577
02:49:50,800 --> 02:49:51,800
ANYONE, ANY OF THE SPEAKERS OR

4578
02:49:51,800 --> 02:49:54,880
ANY OF THE TOPICS THAT ARE OF

4579
02:49:54,880 --> 02:50:00,800
INTEREST OR ANY BROAD QUESTION.

4580
02:50:00,800 --> 02:50:05,520
>> YES, I HAVE A QUESTION FOR

4581
02:50:05,520 --> 02:50:07,080
MARION, I WANTED TO ASK THEN,

4582
02:50:07,080 --> 02:50:09,120
THIS VERY INTERESTING FIRST OF

4583
02:50:09,120 --> 02:50:11,400
ALL REALLY ENJOYED YOUR

4584
02:50:11,400 --> 02:50:13,400
PRESENTATION VERY NICE DATA.

4585
02:50:13,400 --> 02:50:17,560
THE VERY INTERESTING EFFECTOR,

4586
02:50:17,560 --> 02:50:19,880
BY THAT I MEAN THE CYTOKINE

4587
02:50:19,880 --> 02:50:22,800
PRODUCING POTENTIAL OF THE

4588
02:50:22,800 --> 02:50:25,480
T-CELLS, IN THE PRE-INFECTED

4589
02:50:25,480 --> 02:50:27,760
VERSUS VACCINATED AND YOU SHOWED

4590
02:50:27,760 --> 02:50:30,280
INTERFERON GAMMA AND IL 10,

4591
02:50:30,280 --> 02:50:32,320
GRANTED THESE ARE PERIPHERAL

4592
02:50:32,320 --> 02:50:34,440
T-CELLS, BUT WHAT IS THE

4593
02:50:34,440 --> 02:50:37,400
PHENOTYPE, ARE THESE ALL RO

4594
02:50:37,400 --> 02:50:41,040
POSITIVE OR SIMULTANEOUS?

4595
02:50:41,040 --> 02:50:43,960
>> THANKS, IT IS A COMBINATION,

4596
02:50:43,960 --> 02:50:45,240
THEY ARE -- I DIDN'T HAVE TIME

4597
02:50:45,240 --> 02:50:48,840
TO GO INTO THAT DATA.

4598
02:50:48,840 --> 02:50:51,120
MOST OF THE CELLS LOOK LIKE

4599
02:50:51,120 --> 02:50:54,240
EFFECTOR MEMORY CELLS.

4600
02:50:54,240 --> 02:50:57,520
SO NOTHING SUPER EXCITING ABOUT

4601
02:50:57,520 --> 02:50:59,120
THEM AND WE LOOK AT ALL THE

4602
02:50:59,120 --> 02:51:01,440
CHEMOKINE RECEPTORS AND TO

4603
02:51:01,440 --> 02:51:02,640
IDENTIFY IF THERE WAS SOMETHING

4604
02:51:02,640 --> 02:51:06,240
UNIQUE ABOUT THEM BUT THEY LOOK

4605
02:51:06,240 --> 02:51:08,520
PRETTY MUCH GENERIC EFFECTOR

4606
02:51:08,520 --> 02:51:09,040
MEMORY CELLS.

4607
02:51:09,040 --> 02:51:11,720
>> EVEN IN THE CD8 SUBSET YOU

4608
02:51:11,720 --> 02:51:15,000
SEE MOSTLY THE EFFECT --

4609
02:51:15,000 --> 02:51:16,240
>> NOT IN THE CD8 SUBSET.

4610
02:51:16,240 --> 02:51:19,160
WE DIDN'T DO A LOT WITH THE CD8

4611
02:51:19,160 --> 02:51:19,840
SUBSET.

4612
02:51:19,840 --> 02:51:23,400
OUR PEPTIDE POOLS WERE 15 MERS

4613
02:51:23,400 --> 02:51:26,520
AND WE THINK PROBABLY BETTER AT

4614
02:51:26,520 --> 02:51:28,720
ACTIVATING CD4 CELLS THAN CD8

4615
02:51:28,720 --> 02:51:30,240
CELLS SO WE REALLY DIDN'T FOCUS

4616
02:51:30,240 --> 02:51:31,880
TOO MUCH ON THE CD8 CELLS IN

4617
02:51:31,880 --> 02:51:33,440
THESE ASSAYS.

4618
02:51:33,440 --> 02:51:36,080
BUT FOR THE CD4s THEY WERE

4619
02:51:36,080 --> 02:51:38,800
PRIMARILY EFFECTOR MEMORY CELLS.

4620
02:51:38,800 --> 02:51:40,240
>> IF I COULD HAVE ONE QUESTION

4621
02:51:40,240 --> 02:51:42,000
ADDRESSED TO BOTH YOU AND DONNA

4622
02:51:42,000 --> 02:51:43,360
WHICH IS SOMETHING INTRIGUING

4623
02:51:43,360 --> 02:51:49,680
FOR US, VERY DIFFERENT CONTEXT

4624
02:51:49,680 --> 02:51:53,240
STUDY (INAUDIBLE) (INAUDIBLE)

4625
02:51:53,240 --> 02:51:54,640
ARE NOT THAT WELL STUDIED YET

4626
02:51:54,640 --> 02:51:56,440
YOU SEE THEM IN SOME PATIENTS IN

4627
02:51:56,440 --> 02:51:58,920
GOOD NUMBERS.

4628
02:51:58,920 --> 02:52:01,040
NOW, DO THEY TRAFFIC TO IF LUNG?

4629
02:52:01,040 --> 02:52:03,800
WHAT ARE YOUR THOUGHTS ON WHEN

4630
02:52:03,800 --> 02:52:05,560
THERE IS A KEY, WHEN THERE IS A

4631
02:52:05,560 --> 02:52:07,840
LOCAL INFECTION, THE RRMs ARE

4632
02:52:07,840 --> 02:52:09,680
THERE AND WE CAN BRING UP WHOLE

4633
02:52:09,680 --> 02:52:10,600
DISCUSSION ABOUT THEM

4634
02:52:10,600 --> 02:52:13,440
CIRCULATING BUT HOW ARE THE THEM

4635
02:52:13,440 --> 02:52:13,880
RAS?

4636
02:52:13,880 --> 02:52:14,880
ARE THEY COLD?

4637
02:52:14,880 --> 02:52:17,640
>> SO THE TEMORAS GET TO THE

4638
02:52:17,640 --> 02:52:20,640
LUNG.

4639
02:52:20,640 --> 02:52:23,120
YOU FIND THEM IN THE LUNG.

4640
02:52:23,120 --> 02:52:25,000
BUT -- AND YOU CAN FIND VIRUS

4641
02:52:25,000 --> 02:52:27,800
SPECIFIC IN THE LUNG LIKE TO CMV

4642
02:52:27,800 --> 02:52:30,440
AND WE HAVE DONE ALSO TCR

4643
02:52:30,440 --> 02:52:32,040
SEQUENCING IN DIFFERENT SITES

4644
02:52:32,040 --> 02:52:33,840
AND THEY TEND TO BE HIGHLY

4645
02:52:33,840 --> 02:52:35,240
CLONAL EXPANDED AND THEY ARE

4646
02:52:35,240 --> 02:52:37,240
TRUE CIRCULATING SO THEY HAVE

4647
02:52:37,240 --> 02:52:39,360
THE SAME CLONE.

4648
02:52:39,360 --> 02:52:41,080
EXHIBITS ALMOST COMPLETE OVERLAP

4649
02:52:41,080 --> 02:52:44,080
IN ALL THE SITES FOUND IN.

4650
02:52:44,080 --> 02:52:46,200
SO ABLE TO GET PLACES.

4651
02:52:46,200 --> 02:52:49,720
>> SO THEY CAN BE LODGED THERE

4652
02:52:49,720 --> 02:52:52,240
BUT ALSO PROBABLY CIRCULATE.

4653
02:52:52,240 --> 02:52:52,640
>> YES.

4654
02:52:52,640 --> 02:52:53,320
>> MIC.

4655
02:52:53,320 --> 02:52:53,680
>> THANKS.

4656
02:52:53,680 --> 02:52:56,320
THIS WAS REALLY FUB FOR ME

4657
02:52:56,320 --> 02:52:58,440
BECAUSE WORKING IN AUTOIMMUNE --

4658
02:52:58,440 --> 02:53:00,440
FUN FOR ME BECAUSE I DON'T

4659
02:53:00,440 --> 02:53:01,720
UNDERSTAND AS MUCH ABOUT

4660
02:53:01,720 --> 02:53:02,720
INFECTIOUS DISEASE SO I LEARNED

4661
02:53:02,720 --> 02:53:05,240
A LOT BUT ONE THING I WAS

4662
02:53:05,240 --> 02:53:06,000
WONDERING, THERE HAVE BEEN A

4663
02:53:06,000 --> 02:53:08,120
NUMBER OF REPORTS OF SINGLE CELL

4664
02:53:08,120 --> 02:53:10,880
RAB SEQUENCING ANALYSES IN

4665
02:53:10,880 --> 02:53:13,880
LUNGS, LOOKING AT MILD MODERATE

4666
02:53:13,880 --> 02:53:16,440
SEVERE COVID, I KNOW YOU LOSE

4667
02:53:16,440 --> 02:53:18,080
THE ANTIGEN DEVELOPING TO SEE

4668
02:53:18,080 --> 02:53:19,720
WHICH OF THOSE CELLS ARE ANTIGEN

4669
02:53:19,720 --> 02:53:22,080
SPECIFIC SO IT IS REALLY A VERY

4670
02:53:22,080 --> 02:53:25,440
DIFFERENT CONTEXT BUT I WAS JUST

4671
02:53:25,440 --> 02:53:26,000
ROUNDING WITH CAN YOU LEARN

4672
02:53:26,000 --> 02:53:28,040
ANYTHING LOOKING AT MILD SEVERE

4673
02:53:28,040 --> 02:53:30,000
COVID WHAT IS THE COMPOSITION OF

4674
02:53:30,000 --> 02:53:32,560
THE T-CELL COMPARTMENT IN THE

4675
02:53:32,560 --> 02:53:33,840
LUNG, AND THEN DOES THAT INFORM

4676
02:53:33,840 --> 02:53:36,040
IN ANY WAY, WHAT YOU MIGHT SEE

4677
02:53:36,040 --> 02:53:39,200
IN BLOOD WITH VACCINES, IS

4678
02:53:39,200 --> 02:53:41,040
ANYONE DONE T-CELL SINGLE CELL

4679
02:53:41,040 --> 02:53:43,720
RNA SEQUENCING IN BLOOD OF

4680
02:53:43,720 --> 02:53:44,760
VACCINATED VERSUS INFECTED

4681
02:53:44,760 --> 02:53:45,920
PATIENTS, SO ON?

4682
02:53:45,920 --> 02:53:50,440
IS THAT A HELPFUL CONCEPT OR

4683
02:53:50,440 --> 02:53:52,760
BECAUSE YOU CAN'T DO

4684
02:53:52,760 --> 02:53:55,840
SPECIFICITY, IS IT A MESS

4685
02:53:55,840 --> 02:53:57,960
ANYWAY, CURIOUS WHAT YOU THINK

4686
02:53:57,960 --> 02:53:58,240
ABOUT THAT.

4687
02:53:58,240 --> 02:54:00,280
>>

4688
02:54:00,280 --> 02:54:01,320
>> I CAN ADDRESS THE LUNG

4689
02:54:01,320 --> 02:54:03,560
QUESTION.

4690
02:54:03,560 --> 02:54:07,040
THERE'S BEEN SINGLE CELL

4691
02:54:07,040 --> 02:54:08,440
SEQUENCING OF LUNG FROM AUTOPSY

4692
02:54:08,440 --> 02:54:10,320
SHOWING T-CELLS ABOUT WE HAVE

4693
02:54:10,320 --> 02:54:12,840
DONE IT FROM AIRWAY SAMPLES SO

4694
02:54:12,840 --> 02:54:15,360
WE COLLECTED AIRWAY SAMPLES IN

4695
02:54:15,360 --> 02:54:16,720
SEVERE COVID WHEN PEOPLE ARE

4696
02:54:16,720 --> 02:54:17,240
INTUBATED.

4697
02:54:17,240 --> 02:54:28,160
WHEN THE TUBE IS WASHED OUT --

4698
02:54:28,160 --> 02:54:29,840
(LOST AUDIO) AND WE SHOWED THAT

4699
02:54:29,840 --> 02:54:31,520
BY SINGLE CELL AS WELL AS FLOW.

4700
02:54:31,520 --> 02:54:34,440
SO THEY ARE THERE.

4701
02:54:34,440 --> 02:54:36,040
AND ARE RESPONDING.

4702
02:54:36,040 --> 02:54:38,720
NOW, SINGLE CELL IN THE LUNG

4703
02:54:38,720 --> 02:54:39,880
MILD RECOVERED, I DON'T KNOW IF

4704
02:54:39,880 --> 02:54:41,800
THAT'S BEEN DONE.

4705
02:54:41,800 --> 02:54:46,040
>> BUT THE BLOOD WHETHER SINGLE

4706
02:54:46,040 --> 02:54:48,240
CELL OF THE BLOOD.

4707
02:54:48,240 --> 02:54:50,640
T-CELLS.

4708
02:54:50,640 --> 02:54:52,080
>> WHAT WAS THAT, DONNA?

4709
02:54:52,080 --> 02:54:53,280
I DIDN'T HEAR YOU.

4710
02:54:53,280 --> 02:54:56,040
>> YOU ALSO ASKED ABOUT SINGLE

4711
02:54:56,040 --> 02:54:58,440
CELL OF THE BLOOD AND WHETHER

4712
02:54:58,440 --> 02:55:02,880
THAT'S INFORMATIVE?

4713
02:55:02,880 --> 02:55:04,200
WITH DIFFERENT SEVERITY?

4714
02:55:04,200 --> 02:55:07,280
>> OR I MEAN, WHEN WE LOOK IN

4715
02:55:07,280 --> 02:55:10,400
THE LUNG IN COVID Z AND LIKE IN

4716
02:55:10,400 --> 02:55:12,560
AUTOIMMUNE DISEASE AND OTHER

4717
02:55:12,560 --> 02:55:17,360
TISSUES, THERE ARE BETWEEN 15

4718
02:55:17,360 --> 02:55:20,000
AND 25 CLUSTERS DEPENDING ON

4719
02:55:20,000 --> 02:55:20,560
PARAMETERS.

4720
02:55:20,560 --> 02:55:21,600
IT IS QUITE DIFFERENT FROM

4721
02:55:21,600 --> 02:55:25,800
THINKING ABOUT FROM THE WAY THAT

4722
02:55:25,800 --> 02:55:27,200
YOU HAVE DESCRIBED MANY TERMS OF

4723
02:55:27,200 --> 02:55:29,320
RESIDENT MEMORY AND CLASSICALLY

4724
02:55:29,320 --> 02:55:30,680
DEFINED T-CELL POPULATIONS.

4725
02:55:30,680 --> 02:55:32,200
HERE YOU GET POPULATIONS, YOU

4726
02:55:32,200 --> 02:55:33,760
ARE NOT EXPECTING WE DON'T KNOW

4727
02:55:33,760 --> 02:55:35,840
EXACTLY WHAT THEY ARE, WE DON'T

4728
02:55:35,840 --> 02:55:38,640
KNOW WHAT MANY OF THEM ARE

4729
02:55:38,640 --> 02:55:39,160
DOING.

4730
02:55:39,160 --> 02:55:43,840
JUST CURIOUS, T-CELLS THROUGH

4731
02:55:43,840 --> 02:55:45,720
SINGLE CELL RNA SEQUENCING AND

4732
02:55:45,720 --> 02:55:46,840
HAVE SOME WAY TO CAM PAIR THE

4733
02:55:46,840 --> 02:55:49,440
TISSUE AND I'M -- COMPARE THE

4734
02:55:49,440 --> 02:55:49,960
TISSUES.

4735
02:55:49,960 --> 02:55:51,440
SOUND LIKE NO ONE HAS DONE THAT.

4736
02:55:51,440 --> 02:55:54,040
THERE ARE PUBLISHED PAPERS ON

4737
02:55:54,040 --> 02:55:57,440
COVID PNEUMONIA SHOWING BRON

4738
02:55:57,440 --> 02:55:58,200
KEOGH LAR LAVAGE FOR MILD AND

4739
02:55:58,200 --> 02:55:58,960
SEVERE SO YOU CAN GET

4740
02:55:58,960 --> 02:56:03,920
COMPARISONS AT THE CELLS THERE.

4741
02:56:03,920 --> 02:56:05,920
BUT DON'T MEAN TO BELABOR.

4742
02:56:05,920 --> 02:56:08,040
>> NO, THEY GOOD QUESTIONS,

4743
02:56:08,040 --> 02:56:09,880
DEFINITELY STUDIES DONE STRAIGHT

4744
02:56:09,880 --> 02:56:14,840
ON BLOOD OF ANTIGEN SPECIFIC

4745
02:56:14,840 --> 02:56:19,880
CELLS FROM SIMILAR LAYER AT

4746
02:56:19,880 --> 02:56:20,280
THIS.

4747
02:56:20,280 --> 02:56:22,920
(INAUDIBLE) HAS DONE SOME OF

4748
02:56:22,920 --> 02:56:28,080
THOSE AND THE -- FROM MY

4749
02:56:28,080 --> 02:56:29,480
PERSPECTIVE STUDIES CHALLENGING

4750
02:56:29,480 --> 02:56:31,200
TO INTERPRET FOR COUPLE OF

4751
02:56:31,200 --> 02:56:32,920
REASONS, ONE, TO LACK OF

4752
02:56:32,920 --> 02:56:34,320
KNOWLEDGE ABOUT ANTIGEN

4753
02:56:34,320 --> 02:56:35,960
SPECIFICITY YOU ARE SEEING SHOW

4754
02:56:35,960 --> 02:56:39,840
UP AT INFLAMMATORY SITE AND ARE

4755
02:56:39,840 --> 02:56:41,240
THEY SHOWING UP BECAUSE THEY ARE

4756
02:56:41,240 --> 02:56:42,720
NOT ANTIGEN SPECIFIC CELLS?

4757
02:56:42,720 --> 02:56:45,240
INFLAMMATION KEEPS GOING.

4758
02:56:45,240 --> 02:56:46,840
ARE THEY TON OF ANTIGEN SPECIFIC

4759
02:56:46,840 --> 02:56:47,840
CELLS AND THE OTHER IS YOU

4760
02:56:47,840 --> 02:56:50,120
CHICKEN AND EGG PROBLEM.

4761
02:56:50,120 --> 02:56:52,880
THEY FREQUENTLY THESE PEOPLE ARE

4762
02:56:52,880 --> 02:56:55,360
SAMPLES ALREADY EXTREMELY ILL SO

4763
02:56:55,360 --> 02:56:59,040
WHAT ARE YOU OBSERVING IS CAUSE

4764
02:56:59,040 --> 02:57:00,840
AND EFFECT THAT IS A BIG

4765
02:57:00,840 --> 02:57:02,360
CHALLENGE WITH HUMAN IMMUNOLOGY

4766
02:57:02,360 --> 02:57:04,800
IF YOU CAN'T DO, THAT'S WHERE

4767
02:57:04,800 --> 02:57:08,120
LONGITUDINAL STUDIES COME IN.

4768
02:57:08,120 --> 02:57:08,960
WITH GREAT STRENGTH THERE.

4769
02:57:08,960 --> 02:57:12,760
IT WAS A LITTLE BIT OF THAT FROM

4770
02:57:12,760 --> 02:57:14,240
CHICAGO GROUP BUT NOT MUCH

4771
02:57:14,240 --> 02:57:15,400
BECAUSE IT WAS EXTREMELY HARD TO

4772
02:57:15,400 --> 02:57:20,440
DO.

4773
02:57:20,440 --> 02:57:23,640
>> I WAS REALLY STRUCK BY

4774
02:57:23,640 --> 02:57:27,040
JULIE'S POPULATION HAVING 32%

4775
02:57:27,040 --> 02:57:29,840
LONG HAULERS.

4776
02:57:29,840 --> 02:57:32,040
I WAS WONDERING IF WE CAN CIRCLE

4777
02:57:32,040 --> 02:57:33,880
BACK AND TALK -- IS THERE A

4778
02:57:33,880 --> 02:57:37,520
CONSENSUS THEN GROWING CONSENSUS

4779
02:57:37,520 --> 02:57:39,520
ON WHAT IS GOING ON, DEPOT OF

4780
02:57:39,520 --> 02:57:42,440
ANTIGEN, HOW DOES THE FIELD

4781
02:57:42,440 --> 02:57:43,880
GOING TO PURSUE UNDERSTANDING

4782
02:57:43,880 --> 02:57:47,440
THIS PROBLEM?

4783
02:57:47,440 --> 02:57:49,800
>> THIS IS JULIE.

4784
02:57:49,800 --> 02:57:51,200
I WILL START BUT OTHERS HAVE

4785
02:57:51,200 --> 02:57:53,280
OPINIONS.

4786
02:57:53,280 --> 02:57:58,680
>> I THINK THAT IT IS TAKEN

4787
02:57:58,680 --> 02:58:00,600
NUMBER -- A YEAR TO FIGURE OUT

4788
02:58:00,600 --> 02:58:06,440
WHAT CAN BE DEFINITION.

4789
02:58:06,440 --> 02:58:09,560
OF THIS BECAUSE THE WAY THEY

4790
02:58:09,560 --> 02:58:16,080
MANIFEST ARE MULTIPLE SYSTEMS.

4791
02:58:16,080 --> 02:58:18,480
WHO MARRY CARD YES VAS QUEUE

4792
02:58:18,480 --> 02:58:20,160
LAWYER NEUROLOGIC, THERE ARE A

4793
02:58:20,160 --> 02:58:20,920
LOT OF THEM.

4794
02:58:20,920 --> 02:58:24,400
THEY VARY BY SEVERITY OF THOSE

4795
02:58:24,400 --> 02:58:25,040
SYMPTOMS.

4796
02:58:25,040 --> 02:58:27,400
SOME ARE NOT NECESSARILY -- SOME

4797
02:58:27,400 --> 02:58:28,680
ARE PERSISTENT FROM ORIGINAL

4798
02:58:28,680 --> 02:58:29,520
INFECTION AND SOME START ALL

4799
02:58:29,520 --> 02:58:33,160
OVER.

4800
02:58:33,160 --> 02:58:34,880
ONCE PERSON HAS SEEMINGLY

4801
02:58:34,880 --> 02:58:36,240
RECOVERED.

4802
02:58:36,240 --> 02:58:39,360
SO I THINK THOSE -- THE ANSWER

4803
02:58:39,360 --> 02:58:42,640
TO YOUR QUESTION MY VIEW WILL

4804
02:58:42,640 --> 02:58:46,840
COME BUT IT IS STILL TAKING SOME

4805
02:58:46,840 --> 02:58:49,840
TIME TO UNDERSTAND WHAT IS THIS

4806
02:58:49,840 --> 02:58:51,240
DISEASE OR THIS DISEASE GROUP.

4807
02:58:51,240 --> 02:58:53,240
AND HOW BEST CAN WE STUDY

4808
02:58:53,240 --> 02:58:57,240
BECAUSE OTHERWISE I THINK IT'S

4809
02:58:57,240 --> 02:58:59,840
GOING TO GETS A VARIETY OF

4810
02:58:59,840 --> 02:59:01,440
THINGS THAT MAY NOT PAN OUT.

4811
02:59:01,440 --> 02:59:02,600
THERE ARE OBVIOUSLY GOOD PAPERS

4812
02:59:02,600 --> 02:59:06,040
COMING OUT THAT ARE LOOKING AT

4813
02:59:06,040 --> 02:59:08,040
THAT EVEN JUST OVER THE LAST

4814
02:59:08,040 --> 02:59:09,280
WEEK TO TRY TO TEASE THAT APART

4815
02:59:09,280 --> 02:59:12,520
MORE.

4816
02:59:12,520 --> 02:59:15,000
BUT I THINK IT IS GOING TO TAKE

4817
02:59:15,000 --> 02:59:15,520
MORE TIME.

4818
02:59:15,520 --> 02:59:16,720
THAT IS MY VIEW.

4819
02:59:16,720 --> 02:59:21,360
SO IN OUR GROUP IT WAS ABOUT 30%

4820
02:59:21,360 --> 02:59:23,440
AND THERE'S SOME THAT WERE

4821
02:59:23,440 --> 02:59:24,560
REALLY SICK AND THERE'S SOME

4822
02:59:24,560 --> 02:59:27,680
THAT ARE REALLY KIND OF MILDLY

4823
02:59:27,680 --> 02:59:32,120
SICK AND EVENTUALLY GOING TO GET

4824
02:59:32,120 --> 02:59:32,360
BETTER.

4825
02:59:32,360 --> 02:59:34,120
>> TO FOLLOW JUDY, ONE OF THE

4826
02:59:34,120 --> 02:59:39,080
QUESTIONS WILL BE ADDRESSING

4827
02:59:39,080 --> 02:59:42,360
FUTURE WORK IN THIS COHORT OF

4828
02:59:42,360 --> 02:59:43,840
460 PATIENTS AND 30% REPORTING

4829
02:59:43,840 --> 02:59:46,760
(INAUDIBLE).

4830
02:59:46,760 --> 02:59:48,800
IS THERE ANY CORRELATION WITH

4831
02:59:48,800 --> 02:59:52,240
ADAPTIVE IMMUNE RESPONSE,

4832
02:59:52,240 --> 02:59:54,760
BECAUSE WE HAVE DOING A DEEP

4833
02:59:54,760 --> 02:59:58,440
DIVE ON ALL ASPECTS OF THE

4834
02:59:58,440 --> 03:00:00,520
PROCESS.

4835
03:00:00,520 --> 03:00:03,920
WE (INAUDIBLE) DETAIL DATA ON

4836
03:00:03,920 --> 03:00:07,880
ADAPTIVE IMMUNITY AND LONG COVID

4837
03:00:07,880 --> 03:00:09,920
SYMPTOMS.

4838
03:00:09,920 --> 03:00:13,000
>> HOW ABOUT ALL ANTIBODY

4839
03:00:13,000 --> 03:00:13,360
RESPONSES.

4840
03:00:13,360 --> 03:00:15,360
>> THAT WOULD BE GOOD.

4841
03:00:15,360 --> 03:00:19,840
THANK YOU FOR REMIND MEG.

4842
03:00:19,840 --> 03:00:22,520
WOULD BE CHECKING TO SEE IF

4843
03:00:22,520 --> 03:00:26,440
THERE IS ANY OF THESE ANY

4844
03:00:26,440 --> 03:00:28,240
CHANGES IN POTENTIAL

4845
03:00:28,240 --> 03:00:28,640
AUTOREACTION.

4846
03:00:28,640 --> 03:00:30,680
>> DO YOU SUSPECT FROM ALL OF

4847
03:00:30,680 --> 03:00:31,920
YOUR I'M ASKING EVERYONE THAT

4848
03:00:31,920 --> 03:00:36,240
THERE IS AN ELEMENT OF DEBATED

4849
03:00:36,240 --> 03:00:39,520
HERE GOING ON LIKE MOLECULAR

4850
03:00:39,520 --> 03:00:41,120
MIMICRY OR REACH OF PERIPHERAL

4851
03:00:41,120 --> 03:00:41,840
TOLERANCE>>

4852
03:00:41,840 --> 03:00:46,560
IS THERE ANY SENSE?

4853
03:00:46,560 --> 03:00:51,680
>> I WOULD AGAINST BREATH OF

4854
03:00:51,680 --> 03:00:52,400
AUTOANTIBODIES OF COVID, THERE

4855
03:00:52,400 --> 03:00:55,680
IS MOLECULAR MEMICRIES ANYWAYS.

4856
03:00:55,680 --> 03:00:56,880
WE CAN SEARCH THE GENOME AND

4857
03:00:56,880 --> 03:01:00,040
LOOK FOR SIMILARITIES THAT ARE

4858
03:01:00,040 --> 03:01:01,520
FIVE AMAY KNOW ACIDS LON.

4859
03:01:01,520 --> 03:01:04,960
THERE'S NO WAY, THAT'S GOT TO BE

4860
03:01:04,960 --> 03:01:06,520
LOSS OF TOLERANCE.

4861
03:01:06,520 --> 03:01:09,040
I DON'T KNOW THERE'S ANY WAY TO

4862
03:01:09,040 --> 03:01:09,560
EXPLAIN.

4863
03:01:09,560 --> 03:01:14,680
>> YOU WOULD WITHOUT INVOKING

4864
03:01:14,680 --> 03:01:18,560
ANTIGEN RECOGNITION ACROSS

4865
03:01:18,560 --> 03:01:20,120
ACTIVITY YOU CAN GET

4866
03:01:20,120 --> 03:01:24,480
INFLAMMATION, INFLAMMATORY

4867
03:01:24,480 --> 03:01:29,400
EFFECTS MODIFY (INAUDIBLE) THAT

4868
03:01:29,400 --> 03:01:33,040
PRE-EXISTING AUTOREACTANTS.

4869
03:01:33,040 --> 03:01:37,240
POTENTIAL TO HAVE MIMICRY.

4870
03:01:37,240 --> 03:01:39,000
IT IS MUCH WORSE ONE CAN

4871
03:01:39,000 --> 03:01:43,400
IMAGINE.

4872
03:01:43,400 --> 03:01:47,000
>> ALL DEPENDS WHAT HAPPENS WHEN

4873
03:01:47,000 --> 03:01:48,880
THAT REAL INFORMATION --

4874
03:01:48,880 --> 03:01:50,000
>> I THINK WHAT (INAUDIBLE) IS

4875
03:01:50,000 --> 03:01:51,720
SO IMPORTANT IS KEY FOR THIS, WE

4876
03:01:51,720 --> 03:01:53,480
LOOKED ACROSS MULTIPLE

4877
03:01:53,480 --> 03:01:55,520
INDIVIDUALS AND WILL IS A LOT OF

4878
03:01:55,520 --> 03:01:56,200
HETEROGENEITY IN THE RESPONSE WE

4879
03:01:56,200 --> 03:02:00,440
ARE SEEING AND WE HAVEN'T SEEN

4880
03:02:00,440 --> 03:02:01,440
ANY ONE PARTICULAR SIGNATURE

4881
03:02:01,440 --> 03:02:05,160
JUMP OUT AT US.

4882
03:02:05,160 --> 03:02:06,840
HA IS GOING TO BE KEY GETTING

4883
03:02:06,840 --> 03:02:10,240
BACK TO WHAT'S GOING ON.

4884
03:02:10,240 --> 03:02:12,240
>> FINDING THESE INFLAMMATORY

4885
03:02:12,240 --> 03:02:13,640
MONOCYTES THAT PERSIST FOR

4886
03:02:13,640 --> 03:02:15,640
SEVERAL MONTHS.

4887
03:02:15,640 --> 03:02:16,480
>> SO EXACTLY.

4888
03:02:16,480 --> 03:02:18,440
I WOULD RATHER YOUR QUESTIONS IS

4889
03:02:18,440 --> 03:02:20,200
AN IMPORTANT ONE BUT CLEARLY THE

4890
03:02:20,200 --> 03:02:22,160
WHOLE INNATE ADAPTIVE IMMUNE

4891
03:02:22,160 --> 03:02:23,720
SYSTEM IS COMPLETELY

4892
03:02:23,720 --> 03:02:24,720
DISREGULATED WITH SOMETHING LIKE

4893
03:02:24,720 --> 03:02:26,440
COVID INFECTION.

4894
03:02:26,440 --> 03:02:30,480
SO THE OUTPUT OF THAT COULD BE

4895
03:02:30,480 --> 03:02:33,200
GENERATION OF AUTOANTIBODIES OF

4896
03:02:33,200 --> 03:02:37,640
SOME KIND BECAUSE TNT IL 6

4897
03:02:37,640 --> 03:02:39,440
INFLAMMATORY CYTOKINES THAT

4898
03:02:39,440 --> 03:02:40,880
AFFECT HOW LYMPHOCYTES

4899
03:02:40,880 --> 03:02:41,440
DIFFERENTIATE.

4900
03:02:41,440 --> 03:02:42,480
AND HOW LONG THEY DIFFERENTIATE

4901
03:02:42,480 --> 03:02:47,040
FOR.

4902
03:02:47,040 --> 03:02:49,360
HOW LONG ANTIBODIES MAINTAIN,

4903
03:02:49,360 --> 03:02:50,640
WHETHER YOU FIND BONE MARROW

4904
03:02:50,640 --> 03:02:52,400
PLASMA CELLS THAT SECRETE

4905
03:02:52,400 --> 03:02:53,400
AUTOANTIBODIES FOR A LONG TIME

4906
03:02:53,400 --> 03:02:57,440
OR IS IT JUST EPISODIC, IT GOES

4907
03:02:57,440 --> 03:02:58,200
AWAY?

4908
03:02:58,200 --> 03:03:05,160
SO IT IS VERY MURKY IN TERMS OF

4909
03:03:05,160 --> 03:03:05,640
WHAT PATHWAY.

4910
03:03:05,640 --> 03:03:07,680
>> RAFI MENTIONED THE INNATE

4911
03:03:07,680 --> 03:03:09,440
CELLS WE CANNOT FORGET BECAUSE

4912
03:03:09,440 --> 03:03:12,120
WE ALSO STUDY THEM IN SEPSIS, MY

4913
03:03:12,120 --> 03:03:13,680
OWN GROUP WHEN MY HUSBAND IS

4914
03:03:13,680 --> 03:03:15,400
ANOTHER -- AND OTHER COLLEAGUES.

4915
03:03:15,400 --> 03:03:19,240
AND THEY CAN BE ESPECIALLY THE

4916
03:03:19,240 --> 03:03:19,880
INTERMEDIATE MONOCYTES ARE

4917
03:03:19,880 --> 03:03:22,120
PRETTY INTERESTING IN TERMS OF

4918
03:03:22,120 --> 03:03:24,160
WHAT THEY UNLEASH.

4919
03:03:24,160 --> 03:03:26,640
>> IT DOES SEEM LIKE SOME OF THE

4920
03:03:26,640 --> 03:03:27,840
LONG HAULERS DON'T NECESSARILY

4921
03:03:27,840 --> 03:03:30,640
RESULT FROM SEVERE INFECTION.

4922
03:03:30,640 --> 03:03:34,160
SO DO WE THINK REALLY A MASSIVE

4923
03:03:34,160 --> 03:03:35,480
BURST OF CYTOKINES MIGHT BE THE

4924
03:03:35,480 --> 03:03:35,680
CASE.

4925
03:03:35,680 --> 03:03:36,960
>> I THINK THAT IS A GOOD

4926
03:03:36,960 --> 03:03:38,240
QUESTION.

4927
03:03:38,240 --> 03:03:41,520
WHEN I THINK THE PERSISTENCE OF

4928
03:03:41,520 --> 03:03:44,920
VIRAL RNA INSIDE A BODY IS

4929
03:03:44,920 --> 03:03:45,720
POORLY UNDERSTAND THE

4930
03:03:45,720 --> 03:03:50,720
PERSISTENCE AND IMPACT OF VIRAL

4931
03:03:50,720 --> 03:03:53,120
RNA HOW LONG IT LASTS WHEN DOES

4932
03:03:53,120 --> 03:03:54,880
ITALIAN AND THE THE IMPACT, WHAT

4933
03:03:54,880 --> 03:03:56,440
INNATE PATHWAYS DOES IT ACTIVATE

4934
03:03:56,440 --> 03:03:59,000
AND THE WHAT IS THE CONCEPT OF

4935
03:03:59,000 --> 03:04:00,240
PERSISTENT INNATE ACTIVATION.

4936
03:04:00,240 --> 03:04:01,640
THAT IS I THINK NEEDS TO BE

4937
03:04:01,640 --> 03:04:04,840
STUDIED AND I THINK IT COULD

4938
03:04:04,840 --> 03:04:06,120
EXPLAIN SOME OF THE LONG HAULER

4939
03:04:06,120 --> 03:04:09,400
PHENOTYPES.

4940
03:04:09,400 --> 03:04:10,480
>> ROSS, QUESTION.

4941
03:04:10,480 --> 03:04:13,000
>> ONE FOR JULIE AND ONE FOR

4942
03:04:13,000 --> 03:04:13,880
EVERYBODY.

4943
03:04:13,880 --> 03:04:15,640
THE LOUNGE HAULER QUESTION I WAS

4944
03:04:15,640 --> 03:04:17,200
STRUCK ON THE DATA THAT THE

4945
03:04:17,200 --> 03:04:20,840
DOMINANT ANTIGEN FOR CD8

4946
03:04:20,840 --> 03:04:24,440
RESPONSES U IS DIRECTED, IF I

4947
03:04:24,440 --> 03:04:27,040
REMEMBER THIS CORRECTLY, ONCE

4948
03:04:27,040 --> 03:04:29,840
IMMUNIZED THAT SUBSEQUENT

4949
03:04:29,840 --> 03:04:31,400
INFECTION, IT WAS DOMINATED BY

4950
03:04:31,400 --> 03:04:32,360
SPIKE BUT WHICH HAS OBVIOUS

4951
03:04:32,360 --> 03:04:33,160
REASONS FOR IT.

4952
03:04:33,160 --> 03:04:36,640
IS THERE ANY -- THERE'S

4953
03:04:36,640 --> 03:04:38,080
ANECDOTAL THOUGHT THAT LONG

4954
03:04:38,080 --> 03:04:41,000
COVID PEOPLE GOT VACCINES WERE

4955
03:04:41,000 --> 03:04:42,360
NOW -- WE ARE SEEING SOME

4956
03:04:42,360 --> 03:04:43,680
BENEFIT FROM THAT IN TERMS OF

4957
03:04:43,680 --> 03:04:45,120
LONG COVID SYMPTOMS.

4958
03:04:45,120 --> 03:04:46,200
ANY THOUGHT -- DO YOU HAVE

4959
03:04:46,200 --> 03:04:48,440
THOUGHTS ABOUT THAT SWITCH IN

4960
03:04:48,440 --> 03:04:49,600
DOMINANT CD8 RESPONSE BETWEEN

4961
03:04:49,600 --> 03:04:51,760
JUST INFECTED VERSUS INFECTIONED

4962
03:04:51,760 --> 03:04:53,280
WITH VACCINE AND WHETHER THAT

4963
03:04:53,280 --> 03:04:53,880
HAS A ROLE?

4964
03:04:53,880 --> 03:04:54,360
IT?

4965
03:04:54,360 --> 03:04:55,840
>> IT'S A GOOD QUESTION.

4966
03:04:55,840 --> 03:05:02,480
AND IN OUR EXPERIENCE WE HAVE

4967
03:05:02,480 --> 03:05:07,760
HAD MEEK DOTELY PEOPLE SAY THEY

4968
03:05:07,760 --> 03:05:08,800
CAN SMELL WHEN GETTING

4969
03:05:08,800 --> 03:05:09,840
ADVANTAGENATED WHEN BEFORE THEY

4970
03:05:09,840 --> 03:05:11,240
COULDN'T FROM THEIR INFECTION.

4971
03:05:11,240 --> 03:05:12,840
AND WE HAVE EVEN HAD PEOPLE WHO

4972
03:05:12,840 --> 03:05:15,000
HAVE GOTTEN THE VACCINE THOUGH

4973
03:05:15,000 --> 03:05:16,640
WHO SAID THEY ARE HAVING

4974
03:05:16,640 --> 03:05:18,920
PROBLEMS WITH THEIR SMELL SO I

4975
03:05:18,920 --> 03:05:20,520
-- IT IS REALLY -- TO ME IT IS

4976
03:05:20,520 --> 03:05:22,360
STILL UP IN THE AIR ABOUT THAT.

4977
03:05:22,360 --> 03:05:26,480
BUT ONE THING I WILL ADD THAT I

4978
03:05:26,480 --> 03:05:28,240
THINK IS ALSO MORE FOOD FOR

4979
03:05:28,240 --> 03:05:29,680
THOUGHT IS WE ARE BEGINNING TO

4980
03:05:29,680 --> 03:05:32,280
LOOK AT THE BREAK THROUGH

4981
03:05:32,280 --> 03:05:34,360
INFECTIONS, WE ARE ALSO SEEING

4982
03:05:34,360 --> 03:05:39,960
JUST BEGINNING TO SEE PERSISTENT

4983
03:05:39,960 --> 03:05:41,320
SYMPTOMS AFTER 60 DAYS.

4984
03:05:41,320 --> 03:05:43,640
THESE ARE ONES THAT WERE NOT

4985
03:05:43,640 --> 03:05:44,280
NECESSARILY INFECTED WITH

4986
03:05:44,280 --> 03:05:46,840
OMICRON BUT FROM THE PAST, WHO

4987
03:05:46,840 --> 03:05:52,160
WERE VACCINATED AND THEN ARE NOW

4988
03:05:52,160 --> 03:05:54,320
DISPLAYING THIS LOUNGE HAUL

4989
03:05:54,320 --> 03:05:54,600
PHENOTYPE.

4990
03:05:54,600 --> 03:05:55,920
SO I'M NOT SURE THE VACCINATION

4991
03:05:55,920 --> 03:06:00,240
IS GOING TO PREVENT IT BUT MAYBE

4992
03:06:00,240 --> 03:06:03,360
IT WILL DECREASE THE OCCURRENCE

4993
03:06:03,360 --> 03:06:04,120
OF IT.

4994
03:06:04,120 --> 03:06:06,440
IT IS STILL WITH US AND I THINK

4995
03:06:06,440 --> 03:06:09,400
THOSE QUESTIONS THAT ARE BEING

4996
03:06:09,400 --> 03:06:10,760
ADDRESSED HERE AND MENTIONED

4997
03:06:10,760 --> 03:06:12,200
HERE ARE GOING TO BE REALLY

4998
03:06:12,200 --> 03:06:12,440
IMPORTANT.

4999
03:06:12,440 --> 03:06:14,240
TO TRY TO --

5000
03:06:14,240 --> 03:06:17,120
>> MAYBE I COULD ASK A QUICK

5001
03:06:17,120 --> 03:06:18,040
QUESTION TO THE GROUP, SOMETHING

5002
03:06:18,040 --> 03:06:20,920
SIMILAR TO THE LONG HAULER

5003
03:06:20,920 --> 03:06:22,400
PHENOTYPES WE SEE WITH COVID,

5004
03:06:22,400 --> 03:06:24,240
HAS THAT BEEN SEEN WITH ANY

5005
03:06:24,240 --> 03:06:25,440
OTHER INFECTIOUS DISEASE?

5006
03:06:25,440 --> 03:06:26,920
THIS IS AN ACUTE VIRAL

5007
03:06:26,920 --> 03:06:27,520
INFECTION.

5008
03:06:27,520 --> 03:06:29,200
WE BELIEVE THE VIRUS IS CLEARED

5009
03:06:29,200 --> 03:06:32,040
QUITE QUICKLY THOUGH RNA MIGHT

5010
03:06:32,040 --> 03:06:32,440
PERSIST.

5011
03:06:32,440 --> 03:06:34,520
>> CHICKEN GUNIA COMES TO MIND.

5012
03:06:34,520 --> 03:06:34,920
>> RIGHT.

5013
03:06:34,920 --> 03:06:36,440
>> BUT ALSO EBV.

5014
03:06:36,440 --> 03:06:39,360
>> EBV.

5015
03:06:39,360 --> 03:06:43,240
>> MONONUCLEOSIS TYPE.

5016
03:06:43,240 --> 03:06:46,240
>> (INAUDIBLE) QUITE SEVERE,

5017
03:06:46,240 --> 03:06:47,520
MASSIVE (INAUDIBLE) (OVERLAPPING

5018
03:06:47,520 --> 03:06:47,800
SPEAKERS)

5019
03:06:47,800 --> 03:06:51,160
>> DURING THE ACUTE PHASE.

5020
03:06:51,160 --> 03:06:53,840
>> ESPECIALLY FOR THE ELDERLY,

5021
03:06:53,840 --> 03:06:55,800
FLU IS (OVERLAPPING SPEAKERS)

5022
03:06:55,800 --> 03:07:01,640
>> EVEN FOR THE YOUNG.

5023
03:07:01,640 --> 03:07:03,320
-- REASONABLE PROBABILITY THAT

5024
03:07:03,320 --> 03:07:06,040
YOU GET MASSIVE INFECTION AND

5025
03:07:06,040 --> 03:07:09,240
HUGE EXPANSION OF ANTIGEN

5026
03:07:09,240 --> 03:07:10,560
SPECIFIC (INAUDIBLE).

5027
03:07:10,560 --> 03:07:12,800
T-CELL RESPONSE DURING IM, 50%

5028
03:07:12,800 --> 03:07:15,240
OF CD8 T-CELLS.

5029
03:07:15,240 --> 03:07:16,720
>> IT WILL BE INTERESTING TO

5030
03:07:16,720 --> 03:07:18,240
CLASSIFY THE VIRUS AS BASED ON

5031
03:07:18,240 --> 03:07:20,040
WHICH ONES TYPICALLY SHOWN TO

5032
03:07:20,040 --> 03:07:21,360
HAVE SOME SORT OF LONG HAULER

5033
03:07:21,360 --> 03:07:22,840
AND WHAT ARE THE PROPERTIES OF

5034
03:07:22,840 --> 03:07:29,280
THESE VIRUSES AND WHY -- I THINK

5035
03:07:29,280 --> 03:07:29,440
--

5036
03:07:29,440 --> 03:07:32,680
>> ON CHICKEN GUNIA YOU HAVE

5037
03:07:32,680 --> 03:07:35,240
PERSISTENCE OF RNA LIKE TALKING

5038
03:07:35,240 --> 03:07:38,600
ABOUT BALI BUT YOU DON'T HAVE

5039
03:07:38,600 --> 03:07:41,120
ANY CULTURABLE VIRUS BUT YOU DO

5040
03:07:41,120 --> 03:07:43,120
HAVE PERSISTENCE OF MESSENGER

5041
03:07:43,120 --> 03:07:45,720
RNA, RNA IN THE TISSUE AND

5042
03:07:45,720 --> 03:07:48,240
RHEUMATOID ARTHRITIS TYPE

5043
03:07:48,240 --> 03:07:50,200
SYMPTOMS WHICH CAN GO ON QUITE

5044
03:07:50,200 --> 03:07:50,920
SOME TIME.

5045
03:07:50,920 --> 03:07:52,880
>> SHANE DID YOU HAVE A

5046
03:07:52,880 --> 03:07:53,640
QUESTION?

5047
03:07:53,640 --> 03:07:54,520
YOU HAND YOUR HAND UP.

5048
03:07:54,520 --> 03:07:58,080
>> I WAS GOING TO SAY TO ME FROM

5049
03:07:58,080 --> 03:07:59,200
THE COVID-19 PERSPECTIVE THE

5050
03:07:59,200 --> 03:08:02,200
MOST STRIKING DATA I HAVE SEEN

5051
03:08:02,200 --> 03:08:07,600
ON IT IS DEATH BIOPSY DATA, 90

5052
03:08:07,600 --> 03:08:08,360
DAYS OUT FROM NON-(INAUDIBLE)

5053
03:08:08,360 --> 03:08:10,280
CASES AND MAJORITY OF PEOPLE

5054
03:08:10,280 --> 03:08:12,200
STILL HAD BOTH VIRAL RNA AND

5055
03:08:12,200 --> 03:08:14,840
VIRAL PROTEIN, THESE ARE IN

5056
03:08:14,840 --> 03:08:17,720
SMALL GUT BIOPSIES OF VERY TINY

5057
03:08:17,720 --> 03:08:20,120
SECTION OF GUT WHICH SUGGESTED

5058
03:08:20,120 --> 03:08:22,120
THREE MONTHS OUT THE VIRUS IS

5059
03:08:22,120 --> 03:08:23,800
STILL EASILY DETECTABLE IN

5060
03:08:23,800 --> 03:08:27,680
MAJORITY OF PEOPLE AND

5061
03:08:27,680 --> 03:08:28,960
INDEPENDENT OF LONG COVID

5062
03:08:28,960 --> 03:08:30,480
SUGGESTING JUST LOOK AT ONE

5063
03:08:30,480 --> 03:08:31,800
TISSUE IT IS DIFFICULT TO

5064
03:08:31,800 --> 03:08:33,320
COMPLETELY ELIMINATE ALL VIRAL

5065
03:08:33,320 --> 03:08:37,280
MATERIAL WHICH I FINE PERPLEXING

5066
03:08:37,280 --> 03:08:38,040
AND I WOULDN'T FEEL LIKE YOU

5067
03:08:38,040 --> 03:08:39,880
WOULD HAVE TO INVOKE MUCH ELSE

5068
03:08:39,880 --> 03:08:42,840
TO SAY YEAH, YOU COULD HAVE

5069
03:08:42,840 --> 03:08:44,440
SEQUELAE FOR A LONG TIME IF

5070
03:08:44,440 --> 03:08:46,960
THERE IS STILL MATERIAL THERE.

5071
03:08:46,960 --> 03:08:49,440
SO I WOULD LOVE TO SEE A STUDY

5072
03:08:49,440 --> 03:08:51,960
TRACKING STOOL SAMPLES FROM A

5073
03:08:51,960 --> 03:08:54,040
LOT OF PEOPLE LONG TERM, WE KNOW

5074
03:08:54,040 --> 03:08:56,840
IT IS A SENSITIVE WAY TO DETECT

5075
03:08:56,840 --> 03:09:01,000
THE VIRUS AND YET I HAVEN'T SEEN

5076
03:09:01,000 --> 03:09:03,720
STUDIES THAT HAVE TRACKED THOSE

5077
03:09:03,720 --> 03:09:06,640
WITH ALONG WITH IMMUNE RESPONSES

5078
03:09:06,640 --> 03:09:09,960
TO SEE GOING BACK TO THIS --

5079
03:09:09,960 --> 03:09:13,680
CHICKEN GUNIA CULTURABLE VERSUS

5080
03:09:13,680 --> 03:09:14,280
NON-CULTURABLE.

5081
03:09:14,280 --> 03:09:15,720
IT IS A SIMPLE WAY TO DETECT IT.

5082
03:09:15,720 --> 03:09:21,440
I HAVEN'T SEEN IT FOLLOWED UP

5083
03:09:21,440 --> 03:09:21,640
MUCH.

5084
03:09:21,640 --> 03:09:25,120
>> PAPERS THAT CAME OUT FROM

5085
03:09:25,120 --> 03:09:27,240
WUHAN, THEY REPORTING POSITIVE

5086
03:09:27,240 --> 03:09:27,400
--

5087
03:09:27,400 --> 03:09:29,640
>> YES SO I JUST MEANT MORE

5088
03:09:29,640 --> 03:09:30,760
RECENTLY LIKE LONG TERM.

5089
03:09:30,760 --> 03:09:31,720
>> LONG TERM.

5090
03:09:31,720 --> 03:09:35,640
>> AND COMPARED TO IMMUNE

5091
03:09:35,640 --> 03:09:36,360
RESPONSES.

5092
03:09:36,360 --> 03:09:41,560
>> IN GENERAL TO BRING UP THIS

5093
03:09:41,560 --> 03:09:46,080
ISSUE FINDING VIRUS IN THE GUT.

5094
03:09:46,080 --> 03:09:49,400
SO WHEN THE CDC KID (INAUDIBLE)

5095
03:09:49,400 --> 03:09:52,720
STUDY SHARE -- DID (INAUDIBLE)

5096
03:09:52,720 --> 03:09:55,920
SHARED -- THE EXPERT LOOKING FOR

5097
03:09:55,920 --> 03:09:57,360
VIRUS IN TISSUES.

5098
03:09:57,360 --> 03:09:59,400
HE FOUND INFECTION WAS

5099
03:09:59,400 --> 03:10:02,880
PREDOMINANTLY (INAUDIBLE).

5100
03:10:02,880 --> 03:10:05,480
DID NOT FIND VIRUS IN OTHER

5101
03:10:05,480 --> 03:10:05,920
TISSUES.

5102
03:10:05,920 --> 03:10:11,520
BUT THE MASSIVE INFECTION AND

5103
03:10:11,520 --> 03:10:13,840
(INAUDIBLE) PUZZLE BY WHY IT IS

5104
03:10:13,840 --> 03:10:15,280
NOT THE SITE OF THE PRIMARY

5105
03:10:15,280 --> 03:10:16,440
INFECTION.

5106
03:10:16,440 --> 03:10:21,360
WHY WOULD IT PERSIST IN A SITE

5107
03:10:21,360 --> 03:10:25,320
WHERE -- JUST DOESN'T ADD UP.

5108
03:10:25,320 --> 03:10:27,360
>> IS IT POSSIBLE CIRCULATING

5109
03:10:27,360 --> 03:10:28,640
CELLS LIKE MONOCYTES IN THE LUNG

5110
03:10:28,640 --> 03:10:28,800
--

5111
03:10:28,800 --> 03:10:29,560
>> THAT IS POSSIBLE.

5112
03:10:29,560 --> 03:10:30,440
THAT IS POSSIBLE.

5113
03:10:30,440 --> 03:10:34,840
THE OTHER POSSIBILITY IS THAT

5114
03:10:34,840 --> 03:10:37,400
ALSO VIREMIA IN SARS COV-2

5115
03:10:37,400 --> 03:10:39,760
PATIENTS WAS PARTICULARLY LOW

5116
03:10:39,760 --> 03:10:42,840
BUT IN FEW CASES IT WAS SEEN AND

5117
03:10:42,840 --> 03:10:46,080
IT WAS USUALLY SEEN IN THE MOST

5118
03:10:46,080 --> 03:10:46,840
(INAUDIBLE) CASES.

5119
03:10:46,840 --> 03:10:48,840
ONE OF THE HYPOTHESIS AT THAT

5120
03:10:48,840 --> 03:10:50,840
TIME WAS THAT USUALLY FROM

5121
03:10:50,840 --> 03:10:51,880
SOMETHING GROWING IN THE LUNG

5122
03:10:51,880 --> 03:10:54,240
DOESN'T NECESSARILY COME OUT IN

5123
03:10:54,240 --> 03:10:55,320
THE BLOOD.

5124
03:10:55,320 --> 03:10:57,840
DAMAGE TO THE LUNG THAT VIRUS

5125
03:10:57,840 --> 03:10:59,920
WOULD COME OUT.

5126
03:10:59,920 --> 03:11:02,160
MORE (INAUDIBLE) COME OUT

5127
03:11:02,160 --> 03:11:02,680
CIRCULATION.

5128
03:11:02,680 --> 03:11:06,280
IN THAT CASE, THAT COULD HAVE

5129
03:11:06,280 --> 03:11:08,520
RESULTED IN SOME SEEDING IN

5130
03:11:08,520 --> 03:11:10,120
DIFFERENT CASES.

5131
03:11:10,120 --> 03:11:11,600
BUT AGAIN IT WOULD BE SOMETHING

5132
03:11:11,600 --> 03:11:12,680
THAT WOULDN'T NECESSARILY BE

5133
03:11:12,680 --> 03:11:17,160
PICKED UP IN IF AUTOPSY BECAUSE

5134
03:11:17,160 --> 03:11:19,120
THE RANGE OF TISSUE THAT WOULD

5135
03:11:19,120 --> 03:11:20,080
BE THE LUNG SPIKE.

5136
03:11:20,080 --> 03:11:22,240
>> IT'S TRUE BUT SUCCESS IN

5137
03:11:22,240 --> 03:11:24,440
TRACKING THE VIRUS IN WASTE

5138
03:11:24,440 --> 03:11:25,720
WATER AND VARIOUS PLACES MEANS

5139
03:11:25,720 --> 03:11:28,920
THERE IS A HECK OF A LOT GETTING

5140
03:11:28,920 --> 03:11:31,160
THROUGH THE GUT PRETTY QUICKLY

5141
03:11:31,160 --> 03:11:32,240
AND --

5142
03:11:32,240 --> 03:11:35,320
>> AGAIN THERE COULD BE SOME

5143
03:11:35,320 --> 03:11:36,840
SITE (INAUDIBLE) GET CORONA

5144
03:11:36,840 --> 03:11:39,960
VIRUSES IN ANIMAL MODELS, AND

5145
03:11:39,960 --> 03:11:42,040
RECUR DAY TWO INFECT.

5146
03:11:42,040 --> 03:11:44,960
>> HAVE TO LOOK WHERE ACE 2 IS

5147
03:11:44,960 --> 03:11:45,880
RECEPTOR.

5148
03:11:45,880 --> 03:11:50,120
>> (OVERLAPPING SPEAKERS)

5149
03:11:50,120 --> 03:11:54,440
>> SOME RESERVOIR (INAUDIBLE).

5150
03:11:54,440 --> 03:11:57,640
I THINK WE ARE QUITE A BIT OVER.

5151
03:11:57,640 --> 03:12:00,040
SO DONNA, SHOULD WE END THE

5152
03:12:00,040 --> 03:12:02,000
SESSION AND THANK THE -- OUR

5153
03:12:02,000 --> 03:12:02,720
WONDERFUL SPEAKERS?

5154
03:12:02,720 --> 03:12:07,440
>> I THINK ARE THERE ANY LAST

5155
03:12:07,440 --> 03:12:07,920
QUESTIONS?

5156
03:12:07,920 --> 03:12:10,520
I THINK WE HAVE A LOT TO SOLVE.

5157
03:12:10,520 --> 03:12:13,680
I THINK REALLY ALSO JUST

5158
03:12:13,680 --> 03:12:15,680
DEFINING WHAT IS PROTECTION FROM

5159
03:12:15,680 --> 03:12:16,400
ILLNESS TOO BECAUSE I DON'T

5160
03:12:16,400 --> 03:12:18,040
THINK WE ARE THERE.

5161
03:12:18,040 --> 03:12:19,920
WE KNOW IT IS PROTECTION FROM

5162
03:12:19,920 --> 03:12:21,440
DEATH BUT THE VACCINE BUT

5163
03:12:21,440 --> 03:12:22,840
PROTECTION FROM ILLNESS I THINK

5164
03:12:22,840 --> 03:12:25,440
THAT'S LIKE THE FINER LEVEL WE

5165
03:12:25,440 --> 03:12:29,680
NEED TO GET TO.

5166
03:12:29,680 --> 03:12:31,920
ANY LAST COMMENTS ON --

5167
03:12:31,920 --> 03:12:33,720
>> THANKS TO ALL THE SPEAKERS

5168
03:12:33,720 --> 03:12:35,240
AND I THINK GREAT DISCUSSION AND

5169
03:12:35,240 --> 03:12:36,480
GREAT SESSION.

5170
03:12:36,480 --> 03:12:38,400
>> THANK YOU.

5171
03:12:38,400 --> 03:12:40,640
THANKS EVERYONE.

5172
03:12:40,640 --> 03:12:41,440
>>

5173
03:12:41,440 --> 03:12:42,560
>> THANK YOU, ALISON.

5174
03:12:42,560 --> 03:12:44,560
IN YOUR HANDS NOW.

5175
03:12:44,560 --> 03:12:47,360
>> THANK YOU, ALL THE SPEAKERS

5176
03:12:47,360 --> 03:12:51,160
AND DONNA AND RAFI FOR SHARING

5177
03:12:51,160 --> 03:12:52,560
THIS -- CHAIRING THIS SESSION,

5178
03:12:52,560 --> 03:12:55,840
IT'S BEEN A TERRIFIC SESSION.

5179
03:12:55,840 --> 03:12:57,520
WE BEEN WELL WORTH GOING OVER

5180
03:12:57,520 --> 03:13:02,640
THE TIME BUT WE DO NEED NOW TO

5181
03:13:02,640 --> 03:13:04,000
HAVE COUNCIL MEMBERS STAY ON AND

5182
03:13:04,000 --> 03:13:08,160
ANYBODY ELSE IS WELCOME TO, TO

5183
03:13:08,160 --> 03:13:13,000
HEAR THE CONCEPT CLEARANCE

5184
03:13:13,000 --> 03:13:14,560
PROPOSAL THAT KENTNER IS GOING

5185
03:13:14,560 --> 03:13:16,000
TO PRESENT WHILE HE'S GETTING

5186
03:13:16,000 --> 03:13:20,480
HIS SLIDES UP REMIND YOU THAT

5187
03:13:20,480 --> 03:13:24,800
OCCASIONALLY COUNCIL WE HAVE

5188
03:13:24,800 --> 03:13:26,840
CONCEPT CLEARANCE FOR SMALL

5189
03:13:26,840 --> 03:13:28,120
BUSINESS APPLICATIONS THAT WE

5190
03:13:28,120 --> 03:13:30,040
DON'T DISCUSS BUT WE JUST NEED

5191
03:13:30,040 --> 03:13:32,080
TO BRING TO THE PUBLIC'S

5192
03:13:32,080 --> 03:13:34,760
ATTENTION AND WE WILL HAVE THREE

5193
03:13:34,760 --> 03:13:37,280
OF THOSE I WILL MENTION NOW, ONE

5194
03:13:37,280 --> 03:13:40,240
IS ON ADJUVANT DISCOVERY FOR

5195
03:13:40,240 --> 03:13:42,640
VACCINES AND INFECTIOUS IMMUNE

5196
03:13:42,640 --> 03:13:44,520
MEDIATED DISEASES.

5197
03:13:44,520 --> 03:13:47,560
A SECOND IS SIMILAR ADJUVANT

5198
03:13:47,560 --> 03:13:49,240
DEVELOPMENT FOR SAME TOPICS.

5199
03:13:49,240 --> 03:13:53,280
AND A THIRD IS DEVELOPMENT OF

5200
03:13:53,280 --> 03:13:55,280
REAGENTS FOR IMMUNOLOGIC

5201
03:13:55,280 --> 03:13:58,040
ANALYSIS OF NON-MAMMALIAN AND

5202
03:13:58,040 --> 03:13:59,400
UNDER-REPRESENTED MAMMALIAN

5203
03:13:59,400 --> 03:13:59,800
MODELS.

5204
03:13:59,800 --> 03:14:02,440
SO THOSE ARE OUT IN THE PUBLIC

5205
03:14:02,440 --> 03:14:06,240
DOMAIN NOW AND THEY WILL BE

5206
03:14:06,240 --> 03:14:09,080
FUTURE SOLICITATIONS FOR THAT.

5207
03:14:09,080 --> 03:14:12,520
LET'S GO ON NOW TO KENTNER'S

5208
03:14:12,520 --> 03:14:14,840
PRESENTATION THEN WE'LL ASK FOR

5209
03:14:14,840 --> 03:14:18,760
COUNCIL DISCUSSION AND HOPEFULLY

5210
03:14:18,760 --> 03:14:25,040
APPROVAL OF THIS TO GO FORWARD.

5211
03:14:25,040 --> 03:14:29,080
U

5212
03:14:29,080 --> 03:14:32,400
>> I'M PRESENTING CONCEPT FOR FY

5213
03:14:32,400 --> 03:14:32,920
23 KNISH INEFFECTIVE.

5214
03:14:32,920 --> 03:14:35,160
WOULD LIKE THE MOVE FORWARD WITH

5215
03:14:35,160 --> 03:14:36,480
THIS INITIATIVE WHICH IS

5216
03:14:36,480 --> 03:14:39,640
SUPPORTING THE NIAID ADJUVANT

5217
03:14:39,640 --> 03:14:40,480
DEVELOPMENT PROGRAM.

5218
03:14:40,480 --> 03:14:42,440
SO ABOUT 20 YEARS AGO NIAID

5219
03:14:42,440 --> 03:14:44,600
CREATED A PROGRAM TO SUPPORT

5220
03:14:44,600 --> 03:14:45,960
RESEARCH ON VACCINE ADJUVANTS.

5221
03:14:45,960 --> 03:14:50,440
THE REASON FOR THIS, WHILE

5222
03:14:50,440 --> 03:14:51,560
GROUPS ENGAGE IN VACCINE

5223
03:14:51,560 --> 03:14:52,560
DEVELOPMENT RESEARCH EFFORTS

5224
03:14:52,560 --> 03:14:54,640
WERE FOCUSED ON ANTIGEN

5225
03:14:54,640 --> 03:14:57,040
COMPONENT SO THERE IS A REAL

5226
03:14:57,040 --> 03:14:58,720
NEED TO SUPPORT WORK

5227
03:14:58,720 --> 03:15:00,840
SPECIFICALLY ON THE VACCINE

5228
03:15:00,840 --> 03:15:01,680
ADJUVANT SPACE.

5229
03:15:01,680 --> 03:15:04,440
SO IN RESPONSE WE CREATED THE

5230
03:15:04,440 --> 03:15:05,960
ADJUVANT PROGRAM, WHERE THERE IS

5231
03:15:05,960 --> 03:15:07,400
FOUR OBJECTIVES WHICH I LISTED

5232
03:15:07,400 --> 03:15:07,920
HERE.

5233
03:15:07,920 --> 03:15:12,240
THE FIRST IS DISCOVERY, WE NEED

5234
03:15:12,240 --> 03:15:15,120
PA PIPELINE TO EXPAND AND

5235
03:15:15,120 --> 03:15:16,560
BROADEN THE ADJUVANTS FOR NEW

5236
03:15:16,560 --> 03:15:18,160
ADJUVANTS AN EXPLORATION OF

5237
03:15:18,160 --> 03:15:20,240
COMBINATION ADJUVANTS.

5238
03:15:20,240 --> 03:15:21,520
BASIC RESEARCH, THE GOAL HERE IS

5239
03:15:21,520 --> 03:15:23,560
TO BUILD A FOUNDATION SO THAT

5240
03:15:23,560 --> 03:15:25,720
VACCINE DEVELOPERS SELECT BEST

5241
03:15:25,720 --> 03:15:28,160
ADJUVANT FOR THE VACCINE.

5242
03:15:28,160 --> 03:15:29,720
BASED ON THE TARGET.

5243
03:15:29,720 --> 03:15:31,880
GOALS AND PATIENT POPULATION.

5244
03:15:31,880 --> 03:15:34,040
THE THIRD IS PRE-CLINICAL

5245
03:15:34,040 --> 03:15:35,800
DEVELOPMENT, IT TAKES LOT OF

5246
03:15:35,800 --> 03:15:37,160
PRE-CLINICAL DEVELOPMENT WORK TO

5247
03:15:37,160 --> 03:15:38,640
BRING SAFE EFFECTIVE VACCINES

5248
03:15:38,640 --> 03:15:42,040
AND ADJUVANTS TO THE CLINIC.

5249
03:15:42,040 --> 03:15:43,720
INCLUDES FORMULATION STUDIES

5250
03:15:43,720 --> 03:15:45,840
TOXICOLOGY, MANUFACTURING, AND

5251
03:15:45,840 --> 03:15:47,760
THEN PRE-CLINICAL EFFICACY

5252
03:15:47,760 --> 03:15:48,200
STUDIES.

5253
03:15:48,200 --> 03:15:49,840
THERE IS ALSO A NEED TO SUPPORT

5254
03:15:49,840 --> 03:15:51,240
HEAD TO HEAD COMPARISON OF

5255
03:15:51,240 --> 03:15:52,560
VACCINE ADJUVANTS AND

5256
03:15:52,560 --> 03:15:53,400
PRE-CLINICAL MODELS.

5257
03:15:53,400 --> 03:15:54,960
BOTH FOR THE PURPOSE OF DOWN

5258
03:15:54,960 --> 03:15:57,640
SELECTION BUT ALSO TO GOALS

5259
03:15:57,640 --> 03:15:59,320
OUTLINED WITH PAY SICK RESEARCH.

5260
03:15:59,320 --> 03:16:00,640
-- BASIC RESEARCH.

5261
03:16:00,640 --> 03:16:03,040
FINALLY, TO EXPAND ACCESS.

5262
03:16:03,040 --> 03:16:05,040
WE AIM TO ACTIVELY LEVERAGE

5263
03:16:05,040 --> 03:16:07,160
ADJUVANT PROGRAM TO ADVANCE

5264
03:16:07,160 --> 03:16:09,040
NIAID MISSION TOWARD A PROVEN

5265
03:16:09,040 --> 03:16:09,520
GLOBAL HEALTH.

5266
03:16:09,520 --> 03:16:11,520
THIS IS DONE INTERNALLY, BY

5267
03:16:11,520 --> 03:16:15,240
INTERACTING WITH OTHER NIAID NIH

5268
03:16:15,240 --> 03:16:18,880
SUPPORTED PROGRAM BUT EXTERNALLY

5269
03:16:18,880 --> 03:16:21,480
THROUGH INTERACTIONS WITH

5270
03:16:21,480 --> 03:16:22,120
NON-PROFIT ORGANIZATIONS WITHIN

5271
03:16:22,120 --> 03:16:22,880
THE RESEARCH COMMUNITY.

5272
03:16:22,880 --> 03:16:25,080
SO HERE IS HOW WE ARE

5273
03:16:25,080 --> 03:16:26,840
ACCOMPLISHING THESE GOALS.

5274
03:16:26,840 --> 03:16:28,200
UNDER EACH HEADING IS A LIST OF

5275
03:16:28,200 --> 03:16:29,720
NIAID PROGRAMS THAT ADVANCE

5276
03:16:29,720 --> 03:16:32,640
GOALS, ALONG WITH WHEN

5277
03:16:32,640 --> 03:16:34,280
SOLICITATIONS ARE ISSUED OR

5278
03:16:34,280 --> 03:16:35,280
ACTIVITIES CONDUCTED.

5279
03:16:35,280 --> 03:16:38,720
SO IN ADDITION TO THIS SOLICITOR

5280
03:16:38,720 --> 03:16:41,000
PROGRAMS HERE WE HAVE AN ACTIVE

5281
03:16:41,000 --> 03:16:42,240
PORTFOLIO OF GRANTS REWARDED TO

5282
03:16:42,240 --> 03:16:45,920
THE PARENTS RO1 R21 RO 3 AND

5283
03:16:45,920 --> 03:16:47,960
SBIR GRANT MECHANISMS.

5284
03:16:47,960 --> 03:16:49,960
SO FOR DISCOVERY WE HAVE THE

5285
03:16:49,960 --> 03:16:51,200
ADJUVANT DISCOVERY PROGRAM THIS

5286
03:16:51,200 --> 03:16:53,880
IS OUR LONGEST RUNNING ADJUVANT

5287
03:16:53,880 --> 03:16:55,240
PROGRAM.

5288
03:16:55,240 --> 03:16:57,040
BASIC RESEARCH WE HAVE MOLECULAR

5289
03:16:57,040 --> 03:16:58,280
MECHANISMS OF COMBINATION

5290
03:16:58,280 --> 03:16:59,840
ADJUVANT PROGRAM, THIS IS

5291
03:16:59,840 --> 03:17:01,440
RECENTLY RECOMPETED IN A SECOND

5292
03:17:01,440 --> 03:17:02,520
ITERATION WHICH LAUNCHED THIS

5293
03:17:02,520 --> 03:17:04,600
PAST YEAR.

5294
03:17:04,600 --> 03:17:06,840
FOR PRE-CLINICAL DEVELOPMENT THE

5295
03:17:06,840 --> 03:17:08,240
FLAGSHIP PROGRAM IS ADJUVANT

5296
03:17:08,240 --> 03:17:09,840
DEVELOPMENT PROGRAM AND H IS THE

5297
03:17:09,840 --> 03:17:11,560
PROGRAM THAT I'M ASKING THAT WE

5298
03:17:11,560 --> 03:17:12,120
RENEW.

5299
03:17:12,120 --> 03:17:13,800
WE ARE ALSO IN THE PROCESS OF

5300
03:17:13,800 --> 03:17:15,120
LAUNCHING TWO NEW PROGRAMS TO

5301
03:17:15,120 --> 03:17:16,560
SUPPORT THE HEAD TO HEAD

5302
03:17:16,560 --> 03:17:20,120
COMPARISON OF VACCINE ADJUVANTS.

5303
03:17:20,120 --> 03:17:23,440
FINALLY FOR THE EXPANDED --

5304
03:17:23,440 --> 03:17:24,640
EXPANDING ACCESS WE HAVE

5305
03:17:24,640 --> 03:17:25,880
PUBLISHED THE NIAID STRATEGIC

5306
03:17:25,880 --> 03:17:29,240
PLAN FOR RESEARCH ON VACCINE

5307
03:17:29,240 --> 03:17:30,400
ADJUVANTS THIS IS AVAILABLE ON

5308
03:17:30,400 --> 03:17:33,320
OUR WEBSITE, AND ALSO SHOWS UP

5309
03:17:33,320 --> 03:17:34,760
THROUGH WEB SEARCH BUT ALSO

5310
03:17:34,760 --> 03:17:36,680
WITHIN THE PAST YEAR WE LAUNCHED

5311
03:17:36,680 --> 03:17:38,520
THE VACCINE ADJUVANT COMPENDIUM

5312
03:17:38,520 --> 03:17:40,040
WHICH IS ONLINE DATABASE

5313
03:17:40,040 --> 03:17:41,640
DESIGNED TO PROVIDE INFORMATION

5314
03:17:41,640 --> 03:17:42,840
ON ADJUVANTS THAT IS RAILABLE TO

5315
03:17:42,840 --> 03:17:46,000
THE RESEARCH COMMUNITY.

5316
03:17:46,000 --> 03:17:47,720
NOW FOR THE NEXT FEW SLIDES I

5317
03:17:47,720 --> 03:17:49,520
WILL FOCUS FAR MORE JUST ON THE

5318
03:17:49,520 --> 03:17:50,720
ADJUVANT DEVELOPMENT PROGRAM,

5319
03:17:50,720 --> 03:17:52,360
THAT IS THE PROGRAM WE ARE

5320
03:17:52,360 --> 03:17:53,000
ASKING FOB RENEWED.

5321
03:17:53,000 --> 03:17:54,800
SO THE ADJUVANT DEVELOPMENT

5322
03:17:54,800 --> 03:17:56,400
PROGRAM IS EXTREMELY PRODUCTIVE

5323
03:17:56,400 --> 03:17:59,280
WE HAVE MADE SOME VERY NOTABLE

5324
03:17:59,280 --> 03:18:00,400
ACCOMPLISHMENTS THE PAST FEW

5325
03:18:00,400 --> 03:18:01,240
YEARS.

5326
03:18:01,240 --> 03:18:02,720
WE HAVE SUPPORTED THE

5327
03:18:02,720 --> 03:18:05,080
PRE-CLINICAL DEVELOPMENT OF 14

5328
03:18:05,080 --> 03:18:06,680
ADJUVANTS SIX ARE ABOUT 40%

5329
03:18:06,680 --> 03:18:08,040
CURRENTLY SUPPORTED BY THE

5330
03:18:08,040 --> 03:18:11,800
PROGRAM THAT RUNS FROM 2018 TO

5331
03:18:11,800 --> 03:18:12,040
2023.

5332
03:18:12,040 --> 03:18:13,880
SO YOU CAN SEE HERE THAT WE HAVE

5333
03:18:13,880 --> 03:18:15,880
CAST QUITE A WIDE NET OVER THE

5334
03:18:15,880 --> 03:18:21,720
ADJUVANT INCLUDES TLR AGONIST

5335
03:18:21,720 --> 03:18:26,400
NANO EMULSIONS AND CAR E BOW

5336
03:18:26,400 --> 03:18:27,360
HYDRATES AND VERSUS VESICLES.

5337
03:18:27,360 --> 03:18:29,800
50% ENTERED PHASE 1 FIRST IN

5338
03:18:29,800 --> 03:18:30,280
HUMAN CLINICAL TRIALS.

5339
03:18:30,280 --> 03:18:32,880
THE OTHERS ARE WORKING TOWARDS

5340
03:18:32,880 --> 03:18:34,000
THE GOALS, SEVERAL ARE PREPARING

5341
03:18:34,000 --> 03:18:38,200
TO SUBMIT IND PACKAGES TO THE

5342
03:18:38,200 --> 03:18:39,640
FDA IN THE FUTURE SO WE EXPECT

5343
03:18:39,640 --> 03:18:40,200
IT TO INCREASE.

5344
03:18:40,200 --> 03:18:42,040
THEY ARE TESTED IN OVER 25

5345
03:18:42,040 --> 03:18:45,560
CLINICAL TRIALS THAT HAS RANGED

5346
03:18:45,560 --> 03:18:47,640
FROM ALLO IMMUNOTHERAPY, TO

5347
03:18:47,640 --> 03:18:50,240
INFECTIOUS DISEASE, INFLUENZA,

5348
03:18:50,240 --> 03:18:53,640
HIV HEP V E. COLI AND SARS

5349
03:18:53,640 --> 03:18:54,240
COV-2.

5350
03:18:54,240 --> 03:18:56,280
TWO ADJUVANTS TO HIGHLIGHT.

5351
03:18:56,280 --> 03:18:57,720
WHICH ARE BOTH IDENTIFIED

5352
03:18:57,720 --> 03:18:59,040
THROUGH DISCOVERY PROGRAM AND

5353
03:18:59,040 --> 03:19:00,120
ALSO CURRENTLY BEING SUPPORTED

5354
03:19:00,120 --> 03:19:03,240
BY THE DEVELOPMENT PROGRAM OR IN

5355
03:19:03,240 --> 03:19:07,640
COVID VACCINE WITH EUA STATUS.

5356
03:19:07,640 --> 03:19:12,080
FIRST IS HYDROXYQUINN 2 FROM DR.

5357
03:19:12,080 --> 03:19:16,760
DAVID IT IS A TLR 78 AGONIST IN

5358
03:19:16,760 --> 03:19:17,280
KOVAXIN.

5359
03:19:17,280 --> 03:19:20,240
IT WAS DEVELOPED BY A BIOTECH

5360
03:19:20,240 --> 03:19:23,840
APPROVED BY THE WHO AND IS IN

5361
03:19:23,840 --> 03:19:26,120
USE IN 13 COUNTRIES.

5362
03:19:26,120 --> 03:19:27,600
THE COLLABORATION BETWEEN THAT

5363
03:19:27,600 --> 03:19:29,680
AND BROAD BIOTECH WAS CATALYZED

5364
03:19:29,680 --> 03:19:31,200
BY OUTREACH EFFORTS WE MADE

5365
03:19:31,200 --> 03:19:33,600
UNDER THE ENDOUS VACCINE ACTION

5366
03:19:33,600 --> 03:19:34,360
PROGRAM.

5367
03:19:34,360 --> 03:19:38,640
SO THE SECOND IS ADVIX CPG FROM

5368
03:19:38,640 --> 03:19:42,040
DR. NICK PETROSKI.

5369
03:19:42,040 --> 03:19:46,400
A TLR 9 AGONIST USED IN THE

5370
03:19:46,400 --> 03:19:47,000
COVID VACCINE SPIKE GENE WHICH

5371
03:19:47,000 --> 03:19:48,080
IS ACTIVELY USED IN THE MIDDLE

5372
03:19:48,080 --> 03:19:49,600
EAST.

5373
03:19:49,600 --> 03:19:53,240
THE ADJUVANT DEVELOPMENT PROGRAM

5374
03:19:53,240 --> 03:19:55,160
HAS BEEN VERY -- VERY ACTIVELY

5375
03:19:55,160 --> 03:19:58,920
USE THIS TO SUPPORT OTHER NIH

5376
03:19:58,920 --> 03:19:59,640
NIAID PROGRAMS.

5377
03:19:59,640 --> 03:20:01,080
SO WITH WORK WITH NIAID

5378
03:20:01,080 --> 03:20:02,520
COLLEAGUES TO LEVERAGE THE

5379
03:20:02,520 --> 03:20:06,080
PROGRAM, TO ADVANCE THERAPEUTICS

5380
03:20:06,080 --> 03:20:08,200
AND AL LOW GENE THERAPY AND

5381
03:20:08,200 --> 03:20:10,640
DEVELOPMENT OF VACCINES TO TREAT

5382
03:20:10,640 --> 03:20:12,320
OR PREVENT DISEASE, WE USE THIS

5383
03:20:12,320 --> 03:20:13,800
PROGRAM TO SUPPORT EFFORTS

5384
03:20:13,800 --> 03:20:15,560
OUTSIDE OF THE NIAID.

5385
03:20:15,560 --> 03:20:17,240
SO WE HAVE A VERY CLOSE

5386
03:20:17,240 --> 03:20:18,680
COLLABORATION WITH THE NATIONAL

5387
03:20:18,680 --> 03:20:19,640
INSTITUTE OF DRUG ABUSE, OR

5388
03:20:19,640 --> 03:20:21,360
ADJUVANT THERE PROGRAM ARE BEING

5389
03:20:21,360 --> 03:20:23,240
USED FOR THE DEVELOPMENT OF

5390
03:20:23,240 --> 03:20:25,440
VACCINES TO TRY SUBSTANCE USE

5391
03:20:25,440 --> 03:20:26,000
DISORDER.

5392
03:20:26,000 --> 03:20:27,400
WE ALSO COLLABORATE WITH THE

5393
03:20:27,400 --> 03:20:29,240
NATIONAL CANCER INSTITUTE TO

5394
03:20:29,240 --> 03:20:30,200
ADVANCE WORK ON THERAPEUTIC

5395
03:20:30,200 --> 03:20:32,440
CANCER VACCINES.

5396
03:20:32,440 --> 03:20:34,240
FOR THE LAST SLIDE REALLY ABOUT

5397
03:20:34,240 --> 03:20:36,480
THE FY 23 INITIATIVE THAT I

5398
03:20:36,480 --> 03:20:37,520
WOULD LIKE TO CONTINUE.

5399
03:20:37,520 --> 03:20:39,760
THIS IS OUR FLAGSHIP INITIATIVE

5400
03:20:39,760 --> 03:20:41,760
FOR THE ADJUVANT DEVELOPMENT

5401
03:20:41,760 --> 03:20:42,160
PROGRAM.

5402
03:20:42,160 --> 03:20:43,800
ONE CHANGE WE WOULD LIKE TO MAKE

5403
03:20:43,800 --> 03:20:46,720
IS HISTORICALLY THE SOLICITATION

5404
03:20:46,720 --> 03:20:49,000
IS FOCUSED ON DEVELOPMENT OF

5405
03:20:49,000 --> 03:20:50,560
ADJUVANTS WITHIN VACCINES OR

5406
03:20:50,560 --> 03:20:51,280
INFECTIOUS DISEASE.

5407
03:20:51,280 --> 03:20:52,800
FOR THIS ITERATION WE LIKE TO

5408
03:20:52,800 --> 03:20:56,480
OPEN THAT UP TO ALSO ALLOW

5409
03:20:56,480 --> 03:20:57,720
PROPOSALS DEVELOP ADJUVANTS

5410
03:20:57,720 --> 03:20:59,640
WITHIN CONTEXT OF IMMUNE

5411
03:20:59,640 --> 03:21:00,440
MEDIATED DISEASE.

5412
03:21:00,440 --> 03:21:02,440
AS BEFORE, WE WOULD LIKE TO

5413
03:21:02,440 --> 03:21:03,800
SUPPORT THE PRE-CLINICAL

5414
03:21:03,800 --> 03:21:05,240
DEVELOPMENT AND OPTIMIZATION OF

5415
03:21:05,240 --> 03:21:07,640
VACCINE ADJUVANTS NO CHANGES

5416
03:21:07,640 --> 03:21:07,840
HERE.

5417
03:21:07,840 --> 03:21:09,720
WE WOULD ALSO LIKE TO CONTINUE

5418
03:21:09,720 --> 03:21:11,640
TO USE CONTRACT MECHANISM ALLOWS

5419
03:21:11,640 --> 03:21:14,640
GREATER OVERSIGHT AND INCREASE

5420
03:21:14,640 --> 03:21:15,000
FLEXIBILITY.

5421
03:21:15,000 --> 03:21:16,440
THE PERIOD OF PERFORMANCE FOR

5422
03:21:16,440 --> 03:21:18,240
THE CONTRACTS, FIVE YEARS, SO

5423
03:21:18,240 --> 03:21:20,240
THERE'S REALLY NO CHANGE FROM

5424
03:21:20,240 --> 03:21:22,080
THE CURRENT PROGRAM.

5425
03:21:22,080 --> 03:21:23,600
SO I HOPE WE ARE ABLE TO

5426
03:21:23,600 --> 03:21:24,840
CONTINUE WITH THIS PROGRAM, IT

5427
03:21:24,840 --> 03:21:27,320
IS HIGHLY SUCCESSFUL AND REALLY

5428
03:21:27,320 --> 03:21:28,240
QUITE EXCITED TO SEE WHAT IS

5429
03:21:28,240 --> 03:21:29,720
GOING TO HAPPEN WITHIN THE NEXT

5430
03:21:29,720 --> 03:21:30,920
FIVE YEARS.

5431
03:21:30,920 --> 03:21:32,800
SO I'M HAPPY TO ANSWER ANY

5432
03:21:32,800 --> 03:21:33,520
QUESTIONS PEOPLE MIGHT HAVE.

5433
03:21:33,520 --> 03:21:51,000
THANK YOU.

5434
03:21:51,000 --> 03:21:57,040
MARVELOUS, THANK YOU.

5435
03:21:57,040 --> 03:21:58,240
BALI, LOOKED LIKE YOU MIGHT HAVE

5436
03:21:58,240 --> 03:21:58,640
BEEN SPEAKING.

5437
03:21:58,640 --> 03:22:01,240
>> I WAS SPEAKING TO MYSELF.

5438
03:22:01,240 --> 03:22:03,560
>> OKAY.

5439
03:22:03,560 --> 03:22:04,840
WE HAVE ANY OTHER COMMENTS OR

5440
03:22:04,840 --> 03:22:05,680
QUESTIONS?

5441
03:22:05,680 --> 03:22:09,760
>> SEEMS LIKE A WINNER.

5442
03:22:09,760 --> 03:22:10,240
>> APPROVE.

5443
03:22:10,240 --> 03:22:11,000
>> AGREE.

5444
03:22:11,000 --> 03:22:11,880
>> GREAT PROGRAM.

5445
03:22:11,880 --> 03:22:13,360
>> OKAY.

5446
03:22:13,360 --> 03:22:16,360
IN THAT CASE, IN THE INTEREST OF

5447
03:22:16,360 --> 03:22:20,120
TIME LET'S JUST MOVE ON UNLESS

5448
03:22:20,120 --> 03:22:24,040
THERE ARE QUESTIONS TO A MOTION

5449
03:22:24,040 --> 03:22:25,960
TO APPROVE THIS MOVING FORWARD

5450
03:22:25,960 --> 03:22:26,760
IN A SECOND.

5451
03:22:26,760 --> 03:22:27,640
>> SO MOVED.

5452
03:22:27,640 --> 03:22:30,840
>> SECOND.

5453
03:22:30,840 --> 03:22:31,760
>> GREAT.

5454
03:22:31,760 --> 03:22:32,520
THANK YOU ALL.

5455
03:22:32,520 --> 03:22:36,320
THAT LETS US WRAP UP NOW.

5456
03:22:36,320 --> 03:22:39,760
AND I WANT TO ONCE AGAIN THANK

5457
03:22:39,760 --> 03:22:44,480
THE SPEAKERS TODAY FOR JUST A

5458
03:22:44,480 --> 03:22:47,800
REALLY TERRIFIC SET OF

5459
03:22:47,800 --> 03:22:49,400
PRESENTATIONS AND PANEL

5460
03:22:49,400 --> 03:22:51,320
DISCUSSION WHICH WAS REALLY

5461
03:22:51,320 --> 03:22:51,800
NICE.

5462
03:22:51,800 --> 03:22:53,480
>> DAN, IF I COULD ASK THE

5463
03:22:53,480 --> 03:22:55,760
COUNCIL MEMBERS TO VOTE IN THE

5464
03:22:55,760 --> 03:22:56,880
ELECTRONIC COUNCIL BOOK TO

5465
03:22:56,880 --> 03:22:58,600
APPROVE THAT RESEARCH CONCEPT

5466
03:22:58,600 --> 03:22:59,440
CLEARANCE.

5467
03:22:59,440 --> 03:23:02,600
>> JUST TO ADD IF WE COULD ALSO

5468
03:23:02,600 --> 03:23:05,480
APPROVE THE THREE SBIR TOPICS AS

5469
03:23:05,480 --> 03:23:05,680
WELL.

5470
03:23:05,680 --> 03:23:09,400
>> COULD YOU REMIND US WHERE WE

5471
03:23:09,400 --> 03:23:10,520
ACCESS VOTING FOR THOSE?

5472
03:23:10,520 --> 03:23:11,640
I DON'T SEE IT.

5473
03:23:11,640 --> 03:23:14,240
>> IT SHOULD BE THE VOTING

5474
03:23:14,240 --> 03:23:17,000
MATERIALS UNDER THE OPEN SESSION

5475
03:23:17,000 --> 03:23:17,240
SECTION.

5476
03:23:17,240 --> 03:23:19,760
YOU SEE THAT, VOTE ON DOCUMENTS.

5477
03:23:19,760 --> 03:23:20,960
>> OPEN SESSION.

5478
03:23:20,960 --> 03:23:22,600
>> UH-HUH.

5479
03:23:22,600 --> 03:23:25,640
>> OKAY.

5480
03:23:25,640 --> 03:23:27,880
>> WHEN YOU OPEN THE THINGS THAT

5481
03:23:27,880 --> 03:23:29,360
CONTAIN IT IS TEXT BUT NOT WHERE

5482
03:23:29,360 --> 03:23:31,840
TO VOTE.

5483
03:23:31,840 --> 03:23:33,840
>> SHOULD BE TOWARDS TOP OF THE

5484
03:23:33,840 --> 03:23:36,320
PAGE.

5485
03:23:36,320 --> 03:23:38,240
>> ARE OTHERS SEEING IT?

5486
03:23:38,240 --> 03:23:44,320
>> I'M NOT SEEING ALSO.

5487
03:23:44,320 --> 03:23:46,000
>> IF THAT CONTINUES TO BE A

5488
03:23:46,000 --> 03:23:49,040
PROBLEM CAN WE JUST HAVE EMAILS

5489
03:23:49,040 --> 03:23:52,400
SENT TO YVETTE.

5490
03:23:52,400 --> 03:23:52,720
>>

5491
03:23:52,720 --> 03:23:54,120
>> ABSOLUTELY.

5492
03:23:54,120 --> 03:23:56,360
YOU GOT IT.

5493
03:23:56,360 --> 03:24:01,400
>> UNDERSTOOD.

5494
03:24:01,400 --> 03:24:03,360
ANY COMMENTS YOU HAVE AS WELL,

5495
03:24:03,360 --> 03:24:05,000
THOSE COULD ALSO BE CAPTURED BY

5496
03:24:05,000 --> 03:24:07,160
EMAIL.

5497
03:24:07,160 --> 03:24:07,560
GREAT.

5498
03:24:07,560 --> 03:24:08,840
THANK YOU SO MUCH.

5499
03:24:08,840 --> 03:24:12,920
>> LET'S JUST PLAN ON EMAIL TO

5500
03:24:12,920 --> 03:24:14,200
YVETTE, EVERYONE HAS HER ADDRESS

5501
03:24:14,200 --> 03:24:16,320
BUT IF THERE ARE ANY QUESTIONS

5502
03:24:16,320 --> 03:24:18,640
YOU CAN SEND REMINDER IF YOU

5503
03:24:18,640 --> 03:24:19,560
DON'T HEAR FROM ANYBODY.

5504
03:24:19,560 --> 03:24:20,040
>> I WILL.

5505
03:24:20,040 --> 03:24:24,760
>> DID YOU SEE APPROVAL OF THE

5506
03:24:24,760 --> 03:24:25,360
PRE-SBIRs?

5507
03:24:25,360 --> 03:24:29,480
>> THE THREE THAT WAS PREVIOUSLY

5508
03:24:29,480 --> 03:24:30,040
MENTIONED?

5509
03:24:30,040 --> 03:24:32,040
>> WE WOULD LIKE AN OFFICIAL

5510
03:24:32,040 --> 03:24:34,040
VOTE ON THE THREE SBIR TOPICS AS

5511
03:24:34,040 --> 03:24:34,560
WELL.

5512
03:24:34,560 --> 03:24:35,120
>> RIGHT.

5513
03:24:35,120 --> 03:24:40,400
>> MOVE TO APPROVE.

5514
03:24:40,400 --> 03:24:40,880
SPEAKER5: (INAUDIBLE).

5515
03:24:40,880 --> 03:24:41,040
>>

5516
03:24:41,040 --> 03:24:42,520
>> CORRECT.

5517
03:24:42,520 --> 03:24:44,120
>> APPROVAL.

5518
03:24:44,120 --> 03:24:46,880
>> I HAVE TROUBLE WITH THE

5519
03:24:46,880 --> 03:24:50,880
RANKING ONLINE SO I SET MY

5520
03:24:50,880 --> 03:24:51,600
RANKING TO (INAUDIBLE).

5521
03:24:51,600 --> 03:24:54,440
>> THAT'S FINE.

5522
03:24:54,440 --> 03:24:55,840
>> SEND AN EMAIL.

5523
03:24:55,840 --> 03:24:56,720
>> I DID AS WELL.

5524
03:24:56,720 --> 03:25:02,440
SO I WILL DO THAT NOW.

5525
03:25:02,440 --> 03:25:04,600
>> WE SENT FEW MORE TO AMY.

5526
03:25:04,600 --> 03:25:06,000
>> YOU CAN ESSENTIAL TO ME, IF

5527
03:25:06,000 --> 03:25:07,720
YOU SENT TO AMY, IT IS NOT --

5528
03:25:07,720 --> 03:25:10,360
YOU CAN SEND TO ME, IF YOU SENT

5529
03:25:10,360 --> 03:25:11,680
TO AMY THAT IS NOT A PROBLEM.

5530
03:25:11,680 --> 03:25:13,680
WE ALL WORK TOGETHER.

5531
03:25:13,680 --> 03:25:15,520
>> ALL RIGHT.

5532
03:25:15,520 --> 03:25:16,760
THAT'S TERRIFIC.

5533
03:25:16,760 --> 03:25:19,760
THEN THAT ALLOWS US TO WRAP UP

5534
03:25:19,760 --> 03:25:21,160
AND GET ON TO THE REST OF THE

5535
03:25:21,160 --> 03:25:21,600
DAY.

5536
03:25:21,600 --> 03:25:24,040
THANK YOU SO MUCH.

5537
03:25:24,040 --> 03:25:24,520
BYE-BYE

5538
03:25:24,520 --> 03:25:33,640
>> THANK YOU.