1 00:00:05,440 --> 00:00:10,600 >> WELCOME TO TODAY'S COVID-19 2 00:00:10,600 --> 00:00:12,920 SIG SEMINAR. 3 00:00:12,920 --> 00:00:14,680 I'M AT FOOD AND DRUG 4 00:00:14,680 --> 00:00:15,040 ADMINISTRATION. 5 00:00:15,040 --> 00:00:16,680 IT GIVES ME GREAT PLEASURE TO 6 00:00:16,680 --> 00:00:22,360 INTRODUCE A PIONEER IN THE FIELD 7 00:00:22,360 --> 00:00:24,280 OF CORONAVIRUS, DR. MALIK PEIRIS 8 00:00:24,280 --> 00:00:26,760 FROM UNIVERSITY OF HONG KONG, 9 00:00:26,760 --> 00:00:35,720 DEGREE IN MEDICINE SRI LANKA, N 10 00:00:35,720 --> 00:00:39,400 2003 IN THE FIRST SARS OUTBREAK 11 00:00:39,400 --> 00:00:41,000 HE IDENTIFIED AND DISCOVERED THE 12 00:00:41,000 --> 00:00:44,680 NOVEL CORONAVIRUS KNOWN AS THE 13 00:00:44,680 --> 00:00:46,880 FIRST SARS CORONAVIRUS, DURING 14 00:00:46,880 --> 00:00:49,080 THE EPIDEMIC IN HONG KONG 15 00:00:49,080 --> 00:00:56,680 FOLLOWED BY CANADA. 16 00:00:56,680 --> 00:01:00,840 DURING THE COVID PANDEMIC, HE 17 00:01:00,840 --> 00:01:02,000 CONTRIBUTED SEMINAL FINDINGS IN 18 00:01:02,000 --> 00:01:04,360 UNDERSTANDING THE DISEASE AND 19 00:01:04,360 --> 00:01:08,240 LED STUDIES IN HONG KONG. 20 00:01:08,240 --> 00:01:11,000 HE HAS PUBLISHED IN TOP TIER 21 00:01:11,000 --> 00:01:12,840 JOURNALS WITH NUMEROUS AWARDS 22 00:01:12,840 --> 00:01:15,040 AND HONORS, HE'S VERY HUMBLE 23 00:01:15,040 --> 00:01:16,840 ABOUT HIS ACHIEVEMENTS AND 24 00:01:16,840 --> 00:01:18,880 SUPPORTS STUDENTS AND SCIENTISTS 25 00:01:18,880 --> 00:01:20,840 AROUND THE WORLD. 26 00:01:20,840 --> 00:01:22,400 TODAY HE WILL SHARE HIS 27 00:01:22,400 --> 00:01:24,040 EXPERIENCE AND STUDIES TO 28 00:01:24,040 --> 00:01:26,440 COMPARE DIFFERENT FORMS OF 29 00:01:26,440 --> 00:01:29,320 VACCINES INCLUDING mRNA COVID 30 00:01:29,320 --> 00:01:30,960 VACCINES IN HONG KONG. 31 00:01:30,960 --> 00:01:32,720 DR. MALIK, WELCOME. 32 00:01:32,720 --> 00:01:33,520 PLEASE TAKE IT AWAY. 33 00:01:33,520 --> 00:01:35,120 >> THANK YOU FOR THE KIND 34 00:01:35,120 --> 00:01:36,240 INTRODUCTION. I'LL 35 00:01:36,240 --> 00:01:39,320 TALK ABOUT OUR EXPERIENCE IN 36 00:01:39,320 --> 00:01:42,400 HONG KONG, OF THE RNA VACCINES 37 00:01:42,400 --> 00:01:47,760 IN COMPARISON WITH THE WHOLE 38 00:01:47,760 --> 00:01:49,480 VIRUS INACTIVATED VACCINES. 39 00:01:49,480 --> 00:01:55,640 CONFLICTS OF INTEREST, WE HAVE 40 00:01:55,640 --> 00:01:57,160 PATENTS ON USE ON SURVEILLANCE 41 00:01:57,160 --> 00:02:00,560 WITH THE UNIVERSITY AND NOT MY 42 00:02:00,560 --> 00:02:02,320 PERSONAL PROPERTY, SO TO SPEAK. 43 00:02:02,320 --> 00:02:05,600 I MIGHT AS WELL START WITH MY 44 00:02:05,600 --> 00:02:06,560 ACKNOWLEDGMENTS, FUNDING FROM 45 00:02:06,560 --> 00:02:10,280 THE HONG KONG UNIVERSITY GRANTS 46 00:02:10,280 --> 00:02:13,280 COMMITTEE, THE RESEARCH HEALTH 47 00:02:13,280 --> 00:02:17,760 BUREAU, ALSO FROM NIH. 48 00:02:17,760 --> 00:02:21,120 I'LL BE TALKING ABOUT A NUMBER 49 00:02:21,120 --> 00:02:24,080 OF COHORTS, PATIENT COHORTS, ONE 50 00:02:24,080 --> 00:02:27,360 GROUP OF THEM HAVE BEEN 51 00:02:27,360 --> 00:02:28,800 COORDINATED BY BEN, MY 52 00:02:28,800 --> 00:02:31,000 COLLEAGUE, WITH NANCY. 53 00:02:31,000 --> 00:02:33,040 ANOTHER CLINICAL COHORT BY DAVID 54 00:02:33,040 --> 00:02:35,560 HUI AT CHINESE UNIVERSITY OF 55 00:02:35,560 --> 00:02:37,200 HONG KONG, A NEIGHBOR 56 00:02:37,200 --> 00:02:37,640 UNIVERSITY. 57 00:02:37,640 --> 00:02:39,960 AND WE HAVE A PEDIATRIC COHORT I 58 00:02:39,960 --> 00:02:43,240 WON'T HAVE TIME TO TALK ABOUT 59 00:02:43,240 --> 00:02:43,720 TODAY. 60 00:02:43,720 --> 00:02:46,280 AND LABORATORY WORK BY TWO 61 00:02:46,280 --> 00:02:56,720 GRADUATE STUDENTS LARGELY. 62 00:02:58,480 --> 00:03:00,640 THE OUTLINE, I WILL TELL YOU 63 00:03:00,640 --> 00:03:04,840 ABOUT THE HONG KONG EXPERIENCE 64 00:03:04,840 --> 00:03:09,400 WITH COHORTS, RELEVANT TO WHAT 65 00:03:09,400 --> 00:03:12,480 FOLLOWS, BITE MAIN PART WILL BE 66 00:03:12,480 --> 00:03:14,120 COMPARISON OF -- BUT THE MAIN 67 00:03:14,120 --> 00:03:19,360 PART WILL BE COMPARISON. 68 00:03:19,360 --> 00:03:22,000 WHEN I TALK OF THE RNA VIRUS I'M 69 00:03:22,000 --> 00:03:31,960 TALKING ABOUT THE PFIZER 70 00:03:31,960 --> 00:03:33,280 BioNTech VACCINES, 71 00:03:33,280 --> 00:03:34,360 EFFECTIVENESS AND END WITH 72 00:03:34,360 --> 00:03:36,760 IMPLICATIONS FOR CORRELATES OF 73 00:03:36,760 --> 00:03:37,640 PROTECTION. 74 00:03:37,640 --> 00:03:39,920 I DON'T HAVE ANSWERS FOR THAT 75 00:03:39,920 --> 00:03:42,040 CORRELATES OF PROTECTION BUT I 76 00:03:42,040 --> 00:03:45,960 WILL MAYBE RAISE SOME QUESTIONS 77 00:03:45,960 --> 00:03:47,800 ABOUT CURRENT DOGMA REGARDING 78 00:03:47,800 --> 00:03:50,880 CORRELATES OF PROTECTION. 79 00:03:50,880 --> 00:03:55,280 HONG KONG IS A SPECIAL REGION OF 80 00:03:55,280 --> 00:03:59,520 CHINA, OFF THE COAST OF CHINA 81 00:03:59,520 --> 00:04:01,000 HERE, 7.3 MILLION POPULATION, 82 00:04:01,000 --> 00:04:03,680 AND RELEVANT TO THIS, THIS TALK, 83 00:04:03,680 --> 00:04:05,480 THE HEALTH CARE PARTICULARLY FOR 84 00:04:05,480 --> 00:04:06,880 NOVEL AND SEVERE INFECTIOUS 85 00:04:06,880 --> 00:04:08,880 DISEASES FOR THE WHOLE 86 00:04:08,880 --> 00:04:11,280 POPULATION WOULD BE PROVIDED BY 87 00:04:11,280 --> 00:04:13,920 A CENTRAL HOSPITAL AUTHORITY 88 00:04:13,920 --> 00:04:16,520 SYSTEM WITH CLINICAL DATA 89 00:04:16,520 --> 00:04:19,000 CENTRALLY ACCESSIBLE AND 90 00:04:19,000 --> 00:04:20,360 DIGITIZED, HIGHLY CONNECTED 91 00:04:20,360 --> 00:04:21,640 DENSE URBAN POPULATION, GLOBAL 92 00:04:21,640 --> 00:04:22,640 TRAVEL HUB. 93 00:04:22,640 --> 00:04:26,480 DURING COVID OF COURSE 94 00:04:26,480 --> 00:04:28,880 INTERNATIONAL TRAVEL WAS 95 00:04:28,880 --> 00:04:33,920 SEVERELY CURTAILED AND HAS 96 00:04:33,920 --> 00:04:36,120 EXCELLENT FOOD IF YOU WANT TO 97 00:04:36,120 --> 00:04:36,520 VISIT. 98 00:04:36,520 --> 00:04:39,320 THIS SUMMARIZES THE EXPERIENCE 99 00:04:39,320 --> 00:04:40,640 FROM COMMENCEMENT IN JANUARY 100 00:04:40,640 --> 00:04:40,840 2020. 101 00:04:40,840 --> 00:04:44,640 SO FOR TWO YEARS ESSENTIALLY WE 102 00:04:44,640 --> 00:04:46,200 HAD VERY LITTLE COVID, THIS 103 00:04:46,200 --> 00:04:48,080 SHOWS NOTHING BUT THAT IS NOT 104 00:04:48,080 --> 00:04:48,520 TRUE. 105 00:04:48,520 --> 00:04:52,520 JUST THAT THE SCALE IN RELATION 106 00:04:52,520 --> 00:04:54,840 TO THIS PEAK, THE SMALLER PEAKS 107 00:04:54,840 --> 00:04:59,680 YOU SEE HERE ARE INVISIBLE BUT 108 00:04:59,680 --> 00:05:02,000 ESSENTIALLY ALL INTRODUCTIONS 109 00:05:02,000 --> 00:05:03,040 ESSENTIALLY WERE CONTAINED 110 00:05:03,040 --> 00:05:04,400 THROUGH PUBLIC HEALTH MEASURES, 111 00:05:04,400 --> 00:05:07,440 ALTHOUGH WE NEVER HAD A COMPLETE 112 00:05:07,440 --> 00:05:08,040 LOCKDOWN. 113 00:05:08,040 --> 00:05:15,960 SO, BY THE END OF 2021, THE 114 00:05:15,960 --> 00:05:17,840 SEROPREVALENCE WAS WAY LESS THAN 115 00:05:17,840 --> 00:05:19,720 1%, AND THEN IT WAS OMICRON THAT 116 00:05:19,720 --> 00:05:22,920 HIT US AT THAT POINT IN TIME. 117 00:05:22,920 --> 00:05:27,960 INITIALLY IT WAS DELTA THAT WAS 118 00:05:27,960 --> 00:05:28,720 INTRODUCED THROUGH IMPORTED 119 00:05:28,720 --> 00:05:30,000 HAMSTERS, B1 THROUGH RETURNING 120 00:05:30,000 --> 00:05:32,840 AIR CREW, BUT THOSE WERE 121 00:05:32,840 --> 00:05:34,400 CONTAINED AS WELL, BUT IT WAS 122 00:05:34,400 --> 00:05:36,160 BA.2 LEAKING FROM A QUARANTINE 123 00:05:36,160 --> 00:05:38,040 HOTEL THAT LED TO THIS MAJOR 124 00:05:38,040 --> 00:05:38,480 OUTBREAK. 125 00:05:38,480 --> 00:05:41,600 BY THE END OF THAT PARTICULAR 126 00:05:41,600 --> 00:05:43,760 OUTBREAK ABOUT 45% OF THE 127 00:05:43,760 --> 00:05:46,080 POPULATION HAD BEEN INFECTED, 128 00:05:46,080 --> 00:05:47,720 BASED ON SEROPREVALENCE STUDIES 129 00:05:47,720 --> 00:05:48,840 AS WELL. 130 00:05:48,840 --> 00:05:50,720 AND RELEVANT AGAIN TO WHAT I'M 131 00:05:50,720 --> 00:05:55,960 GOING TO TALK ABOUT, MOST ST 132 00:05:55,960 --> 00:05:57,280 SPECIMENS FOR THE STUDIES WHY 133 00:05:57,280 --> 00:05:59,480 COLLECTED PRIOR TO THIS MAJOR 134 00:05:59,480 --> 00:06:02,440 PEAK, SO WHEN THERE WAS VERY 135 00:06:02,440 --> 00:06:03,960 LITTLE VIRUS CIRCULATION, SO 136 00:06:03,960 --> 00:06:06,040 THEREFORE THE DATA IS UNLIKELY 137 00:06:06,040 --> 00:06:09,080 TO BE CONFOUNDED BY UNSUSPECTED 138 00:06:09,080 --> 00:06:09,480 INFECTION. 139 00:06:09,480 --> 00:06:11,440 NOW, THE TWO VACCINES WE'RE 140 00:06:11,440 --> 00:06:15,120 TALKING ABOUT OF COURSE YOU'RE 141 00:06:15,120 --> 00:06:17,960 FAMILIAR WITH PFIZER 142 00:06:17,960 --> 00:06:22,040 BioNTech AND THE OTHER ONE 143 00:06:22,040 --> 00:06:27,840 WAS WHOLE VIRUS INACTIVATED 144 00:06:27,840 --> 00:06:28,520 VACCINE, SINOVAC. 145 00:06:28,520 --> 00:06:32,920 THESE ARE TWO OF THE MOST WIDELY 146 00:06:32,920 --> 00:06:38,480 USED VACCINES GLOBALLY. 147 00:06:38,480 --> 00:06:48,760 THESE ARE THE COHORTS. 148 00:06:48,760 --> 00:06:50,920 DEDICATED COHORTS WERE SET UP 149 00:06:50,920 --> 00:06:53,040 FOR COVID WITH MANY OF THEM WITH 150 00:06:53,040 --> 00:07:00,920 COLLECTING BLOOD SAMPLES, SOME 151 00:07:00,920 --> 00:07:02,440 PBMCs FOR STUDIES, AND TODAY I 152 00:07:02,440 --> 00:07:05,040 WILL BE REFERRING TO SOME OF 153 00:07:05,040 --> 00:07:06,160 THESE COHORTS, AND INCLUDING 154 00:07:06,160 --> 00:07:09,560 VERY BRIEFLY THE BLOOD DONOR 155 00:07:09,560 --> 00:07:10,320 COHORT AS WELL. 156 00:07:10,320 --> 00:07:16,000 THE METHODS WE WERE USING WAS 157 00:07:16,000 --> 00:07:25,760 SPIKE RECEPTOR BINDING DOMAIN 158 00:07:25,760 --> 00:07:27,400 ELISA, SURROGATE NEUTRALIZATION, 159 00:07:27,400 --> 00:07:33,320 BE FC GAMMA RECEPTOR 3 BINDING 160 00:07:33,320 --> 00:07:35,920 ANTIBODIES INDICATORS OF ADCC, 161 00:07:35,920 --> 00:07:44,880 RECEPTOR 2 ANTIBODIES, WHICH IS 162 00:07:44,880 --> 00:07:47,520 INDICATOR OF ADCP, ANTIBODY 163 00:07:47,520 --> 00:07:49,800 AVIDITY AND T-CELL RESPONSES. 164 00:07:49,800 --> 00:07:54,640 SO, VERY EARLY WITHIN A FEW 165 00:07:54,640 --> 00:08:00,000 MONTHS OF VACCINATION WHICH 166 00:08:00,000 --> 00:08:02,720 COMMENCED IN EARLY 2021 IN HONG 167 00:08:02,720 --> 00:08:10,840 KONG DATA SUGGESTED THE 168 00:08:10,840 --> 00:08:11,480 CORONACAV VACCINE PROVIDED 169 00:08:11,480 --> 00:08:13,680 HARDLY ANY RESPONSE, TWO DOSES 170 00:08:13,680 --> 00:08:15,520 HAD MARKED RESPONSE WHETHER 171 00:08:15,520 --> 00:08:18,920 NEUTRALIZATION ANTIBODY RECEPTOR 172 00:08:18,920 --> 00:08:22,200 BINDING DOMAIN, SPIKE ELISA OR 173 00:08:22,200 --> 00:08:25,560 NEUTRALIZATION COMPARED TO RNA 174 00:08:25,560 --> 00:08:26,440 BioNTech VACCINE. 175 00:08:26,440 --> 00:08:31,000 THIS IS A LARGER COHORT SHOWING 176 00:08:31,000 --> 00:08:32,920 THE SAME THING, BioNTech 177 00:08:32,920 --> 00:08:35,680 PROVIDING MUCH HIGHER LEVELS OF 178 00:08:35,680 --> 00:08:37,960 NEUTRALIZING ANTIBODY, AND ALSO 179 00:08:37,960 --> 00:08:41,240 OF COURSE GIVEN THE FACT YOU 180 00:08:41,240 --> 00:08:51,760 START AT LOWER LEVEL ANTIBODY 181 00:08:57,280 --> 00:08:57,640 . 182 00:08:57,640 --> 00:08:58,640 SOME COHORTS WERE CONVALESCENTS 183 00:08:58,640 --> 00:09:01,400 PATIENTS INITIALLY, WE LOOKED AT 184 00:09:01,400 --> 00:09:02,720 WANING ANTIBODY NEUTRALIZING 185 00:09:02,720 --> 00:09:04,120 ANTIBODY IN THESE COHORTS. 186 00:09:04,120 --> 00:09:06,520 AND INDEED PUBLISHED SOME OF THE 187 00:09:06,520 --> 00:09:08,280 EARLY DATA SUGGESTING THAT 188 00:09:08,280 --> 00:09:09,600 NEUTRALIZING ANTIBODY IS LONG 189 00:09:09,600 --> 00:09:11,920 LASTED AND NOT SHORT LASTED, AS 190 00:09:11,920 --> 00:09:14,520 WAS BEING REPORTED FROM SOME OF 191 00:09:14,520 --> 00:09:16,800 THE EARLY STUDIES USING 192 00:09:16,800 --> 00:09:17,720 PSEUDOTYPE NEUTRALIZATION, BUT 193 00:09:17,720 --> 00:09:24,960 THEN CRUCIALLY ARE THE TWO 194 00:09:24,960 --> 00:09:27,200 COHORTS, 350 EACH, NOT 195 00:09:27,200 --> 00:09:30,480 RANDOMIZED BUT BASED ON WHAT 196 00:09:30,480 --> 00:09:32,400 INDIVIDUALS DECIDED TO OPT FOR 197 00:09:32,400 --> 00:09:34,080 OF THE TWO VACCINES. 198 00:09:34,080 --> 00:09:36,000 NOW, BECAUSE THEY WERE NOT 199 00:09:36,000 --> 00:09:39,120 RANDOMIZED WE HAD A SUBSET OF 49 200 00:09:39,120 --> 00:09:41,240 FOR EACH VACCINE, WHICH WAS AGE 201 00:09:41,240 --> 00:09:44,600 MATCHED, AND YOU CAN SEE THE 202 00:09:44,600 --> 00:09:46,480 DEMOGRAPHICS OF THAT COHORT SO 203 00:09:46,480 --> 00:09:48,000 I'LL BE USING BOTH THESE. 204 00:09:48,000 --> 00:09:57,000 SO IF YOU TAKE THIS WHOLE COHORT 205 00:09:57,000 --> 00:09:57,360 COHORT 206 00:09:57,360 --> 00:09:59,600 350, YOU HAVE MARKED DIFFERENCE, 207 00:09:59,600 --> 00:10:02,680 ONE MONTH AFTER THE SECOND DOSE. 208 00:10:02,680 --> 00:10:05,760 AND NOW IF YOU USE THE AGE 209 00:10:05,760 --> 00:10:07,000 MATCHED COHORT ESSENTIALLY YOU 210 00:10:07,000 --> 00:10:10,360 HAVE THE SAME RESULTS. 211 00:10:10,360 --> 00:10:13,720 AND THIS IS NEUTRALIZING PRNT 50 212 00:10:13,720 --> 00:10:14,600 AND 90 LEVELS. 213 00:10:14,600 --> 00:10:18,320 AGAIN YOU CAN SEE SUPERIOR 214 00:10:18,320 --> 00:10:20,960 PERFORMANCE OF THE BioNTech 215 00:10:20,960 --> 00:10:21,320 VACCINE. 216 00:10:21,320 --> 00:10:25,000 WHAT DO THESE BLOOD PRODUCTION 217 00:10:25,000 --> 00:10:27,160 NEUTRALIZATION TEACHERS MEAN? 218 00:10:27,160 --> 00:10:31,440 WE USE THE DATA AND STUDIES FROM 219 00:10:31,440 --> 00:10:33,760 DAVENPORT AND OTHERS PUBLISHED 220 00:10:33,760 --> 00:10:37,480 IN 2021 AND SUBSEQUENTLY WHERE 221 00:10:37,480 --> 00:10:38,680 ESSENTIALLY ESTIMATED CORRELATE 222 00:10:38,680 --> 00:10:42,640 OF 50% PROTECTION FROM 223 00:10:42,640 --> 00:10:44,480 REINFECTION OR BREAKTHROUGH 224 00:10:44,480 --> 00:10:47,360 INFECTION WAS 20% OF THE 225 00:10:47,360 --> 00:10:49,520 CONVALESCENTS NEUTRALIZING 226 00:10:49,520 --> 00:10:50,840 ANTIBODY TITER. 227 00:10:50,840 --> 00:10:53,840 WE USED CONVALESCENT SERA AND ON 228 00:10:53,840 --> 00:10:57,120 THAT BASIS 50% PROTECTION THRESH 229 00:10:57,120 --> 00:11:00,320 ROLLED FOR PRNT 50 WAS 1 IN 26, 230 00:11:00,320 --> 00:11:05,360 AND 50% PROTECTION TITER FOR 231 00:11:05,360 --> 00:11:08,600 PRNT90 WAS 1 IN 8.8 OR 1 IN 9. 232 00:11:08,600 --> 00:11:11,040 I WILL USE THOSE AS THRESHOLDS 233 00:11:11,040 --> 00:11:12,680 OF PROTECTION AS WE GO ALONG. 234 00:11:12,680 --> 00:11:14,520 IF I APPLY THAT TO THE DATA THAT 235 00:11:14,520 --> 00:11:18,040 I SHOWED YOU, YOU CAN SEE THAT 236 00:11:18,040 --> 00:11:23,160 BOTH VACCINES DO BY AND LARGE 237 00:11:23,160 --> 00:11:25,040 LEAD TO NEUTRALIZING ANTIBODY 238 00:11:25,040 --> 00:11:31,720 TITERS ABOVE THRESHOLD OF 239 00:11:31,720 --> 00:11:34,440 PROTECTION PRNT 50 LIES HERE. 240 00:11:34,440 --> 00:11:37,280 THE FACT THE VACCINE IS AT LOWER 241 00:11:37,280 --> 00:11:40,600 LEVEL, THIS WOULD FALL BELOW 242 00:11:40,600 --> 00:11:42,800 THESE PROTECTIVE THRESHOLDS ONE 243 00:11:42,800 --> 00:11:49,440 WOULD EXPECT, FALL BELOW THESE 244 00:11:49,440 --> 00:11:49,840 . 245 00:11:49,840 --> 00:11:59,760 THIS IS THE ELISA, THE SPIKE, 246 00:11:59,760 --> 00:12:00,960 SAME DIFFERENCE AND SPIKE, A 247 00:12:00,960 --> 00:12:01,680 MARKED DIFFERENCE BETWEEN THE 248 00:12:01,680 --> 00:12:03,960 TWO VACCINES. 249 00:12:03,960 --> 00:12:11,160 IF YOU LOOK AT THE SPIKE FC 250 00:12:11,160 --> 00:12:12,120 GAMMA RECEPTOR 3A ANTIBODIES, 251 00:12:12,120 --> 00:12:13,760 AGAIN WE STILL SEE THIS 252 00:12:13,760 --> 00:12:14,800 DIFFERENCE, MARKED DIFFERENCE 253 00:12:14,800 --> 00:12:15,520 BETWEEN THE TWO VACCINES. 254 00:12:15,520 --> 00:12:19,360 BUT ON THE OTHER HAND IF YOU 255 00:12:19,360 --> 00:12:20,440 LOOK AT ANTIBODIES BINDING TO 256 00:12:20,440 --> 00:12:22,640 THE N PROTEIN AS ONE WOULD 257 00:12:22,640 --> 00:12:25,280 EXPECT, WE DO NOT HAVE A 258 00:12:25,280 --> 00:12:26,800 RESPONSE WITH THE RNA VACCINE, 259 00:12:26,800 --> 00:12:30,920 WHEREAS YOU DO HAVE A RESPONSE 260 00:12:30,920 --> 00:12:31,800 WITH THE INACTIVATED VACCINE, 261 00:12:31,800 --> 00:12:34,000 WHICH CONTAINS THE WHOLE VIRUS 262 00:12:34,000 --> 00:12:36,440 AND THEREFORE WILL CONTAIN OTHER 263 00:12:36,440 --> 00:12:39,240 PROTEINS OF THE VIRUS AS WELL. 264 00:12:39,240 --> 00:12:44,960 WHEN WE LOOK AT ANTIBODY AVIDITY 265 00:12:44,960 --> 00:12:48,320 WE SEE ADVANTAGE OF THE RNA 266 00:12:48,320 --> 00:12:52,040 VACCINE HERE, FOR THE FC GAMMA 267 00:12:52,040 --> 00:12:53,360 RECEPTOR 3 ANTIBODY HERE. 268 00:12:53,360 --> 00:12:57,280 THE BINDING AS WELL AS THE 269 00:12:57,280 --> 00:12:58,080 AVIDITY DIFFERENCE. 270 00:12:58,080 --> 00:13:02,360 IF YOU LOOK AT THE BINDING TO 271 00:13:02,360 --> 00:13:09,360 THE N PROTEIN, THEN AGAIN WE 272 00:13:09,360 --> 00:13:11,560 HAVE THE CORONAVAC VACCINE 273 00:13:11,560 --> 00:13:12,720 HAVING SOME ANTIBODY, NOT 274 00:13:12,720 --> 00:13:15,680 PRESENT IN THE RNA VACCINE. 275 00:13:15,680 --> 00:13:18,120 BECAUSE THE NEUTRALIZING 276 00:13:18,120 --> 00:13:21,960 ANTIBODY RESPONSES WITH THE 277 00:13:21,960 --> 00:13:23,560 CORONAVAC WAS RELATIVELY POOR, 278 00:13:23,560 --> 00:13:27,280 WE WERE CONCERNED ABOUT HOW WE 279 00:13:27,280 --> 00:13:33,080 CAN BOOST THAT AND WE TOOK A 280 00:13:33,080 --> 00:13:36,800 SUBSET OF THIS COHORT BASICALLY 281 00:13:36,800 --> 00:13:43,040 THOSE THAT HAVE LOWER ANTIBODY 282 00:13:43,040 --> 00:13:50,800 TITERS, AND RANDOMIZED THEM TO 283 00:13:50,800 --> 00:13:53,640 RECEIVE -- 40 TO RECEIVE 284 00:13:53,640 --> 00:13:54,880 CORONAVAC, 40 BioNTech, AGE 285 00:13:54,880 --> 00:13:57,720 MATCHED SUBSET OF THE WEAK 286 00:13:57,720 --> 00:14:01,440 RESPONDERS TO THE CORONACAV, A 287 00:14:01,440 --> 00:14:06,680 BOOSTER WITH THE SAME VACCINE, 288 00:14:06,680 --> 00:14:09,880 OR RNA VACCINE. 289 00:14:09,880 --> 00:14:12,960 OWN THESE WHO RECEIVED 290 00:14:12,960 --> 00:14:15,880 CORONAVAC, IF THEY GET BOOSTER 291 00:14:15,880 --> 00:14:18,360 THIRD DOSE YOU HAVE MARKED 292 00:14:18,360 --> 00:14:22,040 IMPROVEMENT, THIS IS TO THE 293 00:14:22,040 --> 00:14:23,880 ANCESTRAL VIRUS. 294 00:14:23,880 --> 00:14:26,480 THIS IS A DIFFERENT COHORT, NOW 295 00:14:26,480 --> 00:14:29,200 WE HAVE THE THIRD DOSE OF 296 00:14:29,200 --> 00:14:34,800 BioNTech, AGAIN YOU CAN SEE 297 00:14:34,800 --> 00:14:36,880 ANCESTRAL VIRUS, CORONAVAC AND 298 00:14:36,880 --> 00:14:39,520 BOOSTER IS PRETTY CLOSE TO THREE 299 00:14:39,520 --> 00:14:45,840 DOSES OF BioNTech, BUT THREE 300 00:14:45,840 --> 00:14:52,200 DOSES OF CORONAVAC IS LESS. 301 00:14:52,200 --> 00:14:56,240 SAME FOLLOWS WITH OMICRON 302 00:14:56,240 --> 00:14:57,360 VARIANT, THREE DOSES OF 303 00:14:57,360 --> 00:15:00,600 CORONAVAC LEADS TO VERY LITTLE 304 00:15:00,600 --> 00:15:01,960 NEUTRALIZING ANTIBODY. 305 00:15:01,960 --> 00:15:06,520 AND THIS POINT CONCLUSION WAS 306 00:15:06,520 --> 00:15:09,200 THAT BOOSTER OF BioNTech 307 00:15:09,200 --> 00:15:12,680 WITH TWO DOSES OF CORONAVAC WITH 308 00:15:12,680 --> 00:15:14,440 INTRODUCE HIGH NEUTRALIZING 309 00:15:14,440 --> 00:15:18,400 ANTIBODY AND CROSS-REACTION TO 310 00:15:18,400 --> 00:15:21,760 EMERGING VARIANTS SUCH AS 311 00:15:21,760 --> 00:15:22,000 OMICRON. 312 00:15:22,000 --> 00:15:23,120 LOOKING AT FURTHER VARIANTS, YOU 313 00:15:23,120 --> 00:15:27,560 CAN SEE AGAIN THREE DOSES OF 314 00:15:27,560 --> 00:15:28,440 BioNTech DOES PROVIDE 315 00:15:28,440 --> 00:15:30,000 CROSS-NEUTRALIZATION, EVEN TO 316 00:15:30,000 --> 00:15:35,920 THINGS LIKE BA.4 AND BA.5, 317 00:15:35,920 --> 00:15:38,840 CORONAVAC DOES NOT, BUT TWO 318 00:15:38,840 --> 00:15:40,400 DOSES OF CORONAVAC FOLLOWED BY 319 00:15:40,400 --> 00:15:43,480 BioNTech VERY SIMILAR IN 320 00:15:43,480 --> 00:15:44,880 PATTERN, MAYBE SLIGHTLY LOWER 321 00:15:44,880 --> 00:15:47,440 BUT SIMILAR IN PATTERN TO 322 00:15:47,440 --> 00:15:53,440 VARIANTS, TO THREE DOSES OF 323 00:15:53,440 --> 00:15:54,960 BioNTech. 324 00:15:54,960 --> 00:16:01,920 IN REGARDS TO REACTIVITY, IN 325 00:16:01,920 --> 00:16:07,360 RELATION TO THE SARS CoV 326 00:16:07,360 --> 00:16:09,400 VIRUS, YOU HAVE VARIANTS, 327 00:16:09,400 --> 00:16:16,880 OMICRON IN RECEPTOR BINDING 328 00:16:16,880 --> 00:16:24,000 DOMAIN HAS 93% SIMILARITY. 329 00:16:24,000 --> 00:16:26,720 THIS IS THE BAT CORONAVIRUS, 330 00:16:26,720 --> 00:16:29,920 EVEN MORE DISTANT THAN OMICRON, 331 00:16:29,920 --> 00:16:30,880 AND PANGOLIN, MORE DISTANT, AND 332 00:16:30,880 --> 00:16:33,080 WHEN YOU COME TO SARS 1, MORE 333 00:16:33,080 --> 00:16:35,480 DISTANCE TOO COMPARED TO 334 00:16:35,480 --> 00:16:41,040 ANCESTRAL SARS CORONAVIRUS. 335 00:16:41,040 --> 00:16:43,600 NOW, SOMEONE IN THE DUKE 336 00:16:43,600 --> 00:16:47,280 UNIVERSITY IN SINGAPORE HAD 337 00:16:47,280 --> 00:16:52,320 DEVELOPED A MULTIPLEX SURROGATE 338 00:16:52,320 --> 00:16:57,920 NEUTRALIZATION ASSAY, HE HAD THE 339 00:16:57,920 --> 00:17:00,320 RECEPTOR BINDING DOMAIN OF 340 00:17:00,320 --> 00:17:01,760 SARS-COV-2 VARIANTS AND RELATED 341 00:17:01,760 --> 00:17:06,560 TO BOTH SARS 1 AND SARS 2, ALSO 342 00:17:06,560 --> 00:17:08,880 SARS CORONAVIRUS 1. 343 00:17:08,880 --> 00:17:12,240 WHEN WE USED THAT, IF YOU FOCUS 344 00:17:12,240 --> 00:17:14,880 ON THE THREE DOSES OF 345 00:17:14,880 --> 00:17:18,920 BioNTech FOR EXAMPLE HERE, 346 00:17:18,920 --> 00:17:22,120 AND THAT WOULD BE THIS GROUP 347 00:17:22,120 --> 00:17:25,080 HERE, THESE DARK BARS, SO YOU 348 00:17:25,080 --> 00:17:27,360 CAN SEE THERE'S QUITE HIGH 349 00:17:27,360 --> 00:17:30,640 LEVELS OF SURROGATE NEUTRALIZING 350 00:17:30,640 --> 00:17:36,440 ANTIBODY TO THE ANCESTRAL VIRUS 351 00:17:36,440 --> 00:17:44,640 TO VARIANTS, INTERESTINGLY THE 352 00:17:44,640 --> 00:17:46,280 BAT RaTG13 AND PANGOLIN SARS 353 00:17:46,280 --> 00:17:48,000 CoV VIRUS DOES BETTER WITH 354 00:17:48,000 --> 00:17:49,680 THREE DOSES OF BioNTech IS 355 00:17:49,680 --> 00:17:52,440 NOT SO FAR AWAY FROM SOME OF 356 00:17:52,440 --> 00:17:53,960 THESE VARIANTS. 357 00:17:53,960 --> 00:17:56,120 SO INTERESTINGLY, OMICRON IS 358 00:17:56,120 --> 00:17:58,280 EVEN MORE DIVERGENT, ALTHOUGH IN 359 00:17:58,280 --> 00:18:01,160 TERMS OF SIMILARITY IT IS LESS 360 00:18:01,160 --> 00:18:03,920 DIVERGENT THAN THESE BAT AND 361 00:18:03,920 --> 00:18:06,040 PANGOLIN VIRUSES IN TERMS OF 362 00:18:06,040 --> 00:18:09,920 IMMUNE EVASION, IT IS MORE 363 00:18:09,920 --> 00:18:12,560 DIVERGENT. 364 00:18:12,560 --> 00:18:14,400 SUGGESTING REALLY THAT OMICRON 365 00:18:14,400 --> 00:18:20,320 HAS RISEN THROUGH IMMUNE 366 00:18:20,320 --> 00:18:20,680 EVASION. 367 00:18:20,680 --> 00:18:21,320 YEAH, RIGHT. 368 00:18:21,320 --> 00:18:28,520 AND AGAIN YOU CAN SEE THE 369 00:18:28,520 --> 00:18:30,080 CORONAVIRUS, THE CORONAVAC 370 00:18:30,080 --> 00:18:31,280 BOOSTED WITH BioNTech GIVES 371 00:18:31,280 --> 00:18:33,560 SIMILAR RESULTS. 372 00:18:33,560 --> 00:18:34,440 RIGHT. 373 00:18:34,440 --> 00:18:36,640 NOW, HERE THIS IS AGAIN SIMILAR 374 00:18:36,640 --> 00:18:39,800 RESULTS, NOW THIS IS WITH THREE 375 00:18:39,800 --> 00:18:42,520 DOSES OF BioNTech. 376 00:18:42,520 --> 00:18:44,560 TWO DOSES OF BioNTech HERE. 377 00:18:44,560 --> 00:18:48,440 AND THESE ARE PEOPLE WHO HAD 378 00:18:48,440 --> 00:18:50,400 RECOVERED FROM SARS WITH ONE 379 00:18:50,400 --> 00:18:52,280 DOSE OF BioNTech, AND YOU 380 00:18:52,280 --> 00:18:55,360 CAN SEE THAT JUST A SINGLE DOSE 381 00:18:55,360 --> 00:18:59,080 OF BioNTech INCREASES THE 382 00:18:59,080 --> 00:19:01,440 BREADTH OF PROTECTION ACROSS ALL 383 00:19:01,440 --> 00:19:05,640 THE VARIANTS BUT ALSO THESE BAT 384 00:19:05,640 --> 00:19:10,880 AND PANGOLIN PRECURSORS, SOME 385 00:19:10,880 --> 00:19:14,320 CROSS-REACTIVITY WITH SARS 386 00:19:14,320 --> 00:19:15,600 CORONAVIRUS 1 RELATED WITH SARS 387 00:19:15,600 --> 00:19:16,480 CORONAS WELL. 388 00:19:16,480 --> 00:19:18,760 WHEN WE LOOK AT THOSE WHO 389 00:19:18,760 --> 00:19:21,080 RECOVERED FROM SARS 1, AS YOU 390 00:19:21,080 --> 00:19:23,240 REMEMBER SARS 1 HIT HONG KONG IN 391 00:19:23,240 --> 00:19:27,280 2003, WE GOT SOME OF THOSE 392 00:19:27,280 --> 00:19:30,000 SURVIVORS FROM SARS 1 AND, YOU 393 00:19:30,000 --> 00:19:31,560 KNOW, GOT THEIR VACCINES IN DUE 394 00:19:31,560 --> 00:19:34,520 COURSE, AND YOU CAN SEE SARS 1 395 00:19:34,520 --> 00:19:37,160 EXPOSURE FOLLOWED BY TWO DOSES 396 00:19:37,160 --> 00:19:40,760 OF BioNTech GIVES YOU PRETTY 397 00:19:40,760 --> 00:19:45,040 BROAD COVERAGE ACROSS ALL THESE 398 00:19:45,040 --> 00:19:49,840 SARS VIRUSES INCLUDING BAT 399 00:19:49,840 --> 00:19:50,840 PANGOLN, BUT INDEED OMICRON IS 400 00:19:50,840 --> 00:19:59,160 THE ONE WITH THE WEAKEST 401 00:19:59,160 --> 00:19:59,480 RESPONSE. 402 00:19:59,480 --> 00:20:04,040 COMING BACK TO THE SITUATION AT 403 00:20:04,040 --> 00:20:06,920 THE END OF 2021, BECAUSE WE WERE 404 00:20:06,920 --> 00:20:11,000 QUITE FEARFUL WITH THE MODELS OF 405 00:20:11,000 --> 00:20:13,600 OMICRON THAT THIS GOING TO BREAK 406 00:20:13,600 --> 00:20:14,880 THROUGH INTO HONG KONG, ALTHOUGH 407 00:20:14,880 --> 00:20:17,000 FOR TWO YEARS HAD VERY ALSO 408 00:20:17,000 --> 00:20:18,000 INFECTION, THIS SUMMARIZES WHAT 409 00:20:18,000 --> 00:20:19,880 I TOLD YOU IN TERMS OF DIFFERENT 410 00:20:19,880 --> 00:20:21,880 DOSAGE SCHEDULES BUT IN RELATION 411 00:20:21,880 --> 00:20:24,240 TO OMICRON BA.1 AT THIS POINT IN 412 00:20:24,240 --> 00:20:26,960 TIME, YOU CAN SEE THAT THREE 413 00:20:26,960 --> 00:20:29,480 DOSES WOULD BE REQUIRED TO 414 00:20:29,480 --> 00:20:31,720 PROVIDE PROTECTIVE IMMUNITY, 415 00:20:31,720 --> 00:20:32,600 THREE DOSES OF CORONAVAC WOULD 416 00:20:32,600 --> 00:20:37,360 NOT DO THE JOB. 417 00:20:37,360 --> 00:20:42,040 TWO DOSES CORONAVAC WITH ONE 418 00:20:42,040 --> 00:20:43,160 DOSE OF BioNTech IS 419 00:20:43,160 --> 00:20:45,040 ADEQUATE, AND THOSE WHO 420 00:20:45,040 --> 00:20:46,200 RECOVERED FROM SARS CORONAVIRUS 421 00:20:46,200 --> 00:20:51,920 2 INFECTION A SINGLE DOSE WOULD 422 00:20:51,920 --> 00:20:52,920 GIVE GOOD PROTECTIVE 423 00:20:52,920 --> 00:20:53,760 NEUTRALIZING ANTIBODIES, AGAIN 424 00:20:53,760 --> 00:20:55,960 KEEPING IN MIND THIS IS THE 425 00:20:55,960 --> 00:20:58,400 THRESHOLD OF PROTECTION THAT I 426 00:20:58,400 --> 00:21:04,000 TALKED ABOUT, ARISING FROM MILES 427 00:21:04,000 --> 00:21:05,280 DAVENPORT'S STUDIES. 428 00:21:05,280 --> 00:21:10,000 NOW, IN THE DAVENPORT GROUP, 429 00:21:10,000 --> 00:21:11,520 PROTECTIVE THRESHOLD WAS AGAINST 430 00:21:11,520 --> 00:21:12,440 SYMPTOMATIC INFECTION. 431 00:21:12,440 --> 00:21:15,440 THEY DID TRY TO ESTABLISH 432 00:21:15,440 --> 00:21:19,200 PROTECTIVE THRESHOLD FOR SEVERE 433 00:21:19,200 --> 00:21:23,280 DISEASE BUT CONFIDENCE INTERVALS 434 00:21:23,280 --> 00:21:27,960 WITH LOAD, MAYBE AROUND 1 -- 435 00:21:27,960 --> 00:21:31,360 WERE LOW, 1 IN 3 OR 1 IN 4, YOU 436 00:21:31,360 --> 00:21:32,800 CANNOT ACCURATELY MEASURE IN 437 00:21:32,800 --> 00:21:33,760 NEUTRALIZING ASSAY. 438 00:21:33,760 --> 00:21:39,560 AT THE END OF 2021, WE WERE 439 00:21:39,560 --> 00:21:41,320 QUITE WORRIED BECAUSE A GOOD 440 00:21:41,320 --> 00:21:43,280 PART OF THE POPULATION HAD BEEN 441 00:21:43,280 --> 00:21:47,800 VACCINATED WITH TWO OR THREE 442 00:21:47,800 --> 00:21:51,480 DOSES OF CORONAVAC, AND EVEN IN 443 00:21:51,480 --> 00:21:53,680 SPITE OF THAT, PARTICULARLY THE 444 00:21:53,680 --> 00:21:57,320 OVER 60 AGE GROUP WAS EXTREMELY 445 00:21:57,320 --> 00:21:58,520 VACCINE HESITANT, AND COVERAGE 446 00:21:58,520 --> 00:22:02,640 OF EITHER VACCINE WAS QUITE LOW, 447 00:22:02,640 --> 00:22:13,200 AND INDEED FEARS WERE QUITE WELL 448 00:22:14,200 --> 00:22:16,760 FOUNDS, WHEN OMICRON HIT WE HAD 449 00:22:16,760 --> 00:22:18,280 HIGH LEVELS, PRIMARILY IN THOSE 450 00:22:18,280 --> 00:22:21,120 WHO RECEIVED NO VACCINE AT ALL. 451 00:22:21,120 --> 00:22:23,880 STUDIES WERE DONE DURING THE 452 00:22:23,880 --> 00:22:25,280 OMICRON BA.2 WAVE. 453 00:22:25,280 --> 00:22:27,680 YOU CAN SEE HERE IN TERMS OF 454 00:22:27,680 --> 00:22:31,960 MILD OR MODERATE DISEASE, TWO 455 00:22:31,960 --> 00:22:33,920 DOSES OF EITHER VACCINE 456 00:22:33,920 --> 00:22:35,040 PROVIDING RELATIVELY MODEST OR 457 00:22:35,040 --> 00:22:38,400 NO PROTECTION, BUT THREE DOSES 458 00:22:38,400 --> 00:22:42,040 OF BioNTech AS WE EXPECTED 459 00:22:42,040 --> 00:22:44,560 FROM NEUTRALIZATION STUDIES WAS 460 00:22:44,560 --> 00:22:46,080 PROVIDING REASONABLE PROTECTION 461 00:22:46,080 --> 00:22:48,600 AGAINST MILD INFECTION, BUT WHAT 462 00:22:48,600 --> 00:22:49,920 WAS SURPRISING WAS THAT 463 00:22:49,920 --> 00:22:52,120 CORONAVAC WAS NOT THAT FAR 464 00:22:52,120 --> 00:22:53,800 BEHIND, ALTHOUGH IF YOU'LL JUST 465 00:22:53,800 --> 00:22:54,640 LOOK AT THE NEUTRALIZING DATA 466 00:22:54,640 --> 00:22:59,360 YOU WOULD EXPECT IT TO BE MILES 467 00:22:59,360 --> 00:22:59,600 BEHIND. 468 00:22:59,600 --> 00:23:01,000 AND MOST HAPPILY, IN TERMS OF 469 00:23:01,000 --> 00:23:04,600 PEOPLE WHO HAD THREE DOSES OF 470 00:23:04,600 --> 00:23:06,760 EITHER VACCINE, EITHER 471 00:23:06,760 --> 00:23:08,640 BioNTech OR CORONACAV, THE 472 00:23:08,640 --> 00:23:11,040 PROTECTION FROM SEVERE OR FATAL 473 00:23:11,040 --> 00:23:13,800 DISEASE WAS EXCELLENT. 474 00:23:13,800 --> 00:23:15,120 SO THAT WAS VERY FORTUNATE. 475 00:23:15,120 --> 00:23:18,960 BUT AS I POINT OUT, THERE'S A 476 00:23:18,960 --> 00:23:21,240 MARKED DISCREPANCY BETWEEN THE 477 00:23:21,240 --> 00:23:23,400 VACCINE EFFECTIVENESS AND THE 478 00:23:23,400 --> 00:23:24,520 NEUTRALIZING ANTIBODY TITERS 479 00:23:24,520 --> 00:23:26,800 THAT WE SEE, THAT WAS ONE 480 00:23:26,800 --> 00:23:28,880 VACCINE EFFECTIVENESS STUDY 481 00:23:28,880 --> 00:23:30,360 WHICH IS RETROSPECTIVE STUDY 482 00:23:30,360 --> 00:23:35,800 BASICALLY BUT THIS IS A 483 00:23:35,800 --> 00:23:37,920 PROSPECTIVE COHORTS OF 8600 484 00:23:37,920 --> 00:23:40,520 INDIVIDUALS CONDUCTING WEEKLY 485 00:23:40,520 --> 00:23:43,120 RAPID ANTIGEN TESTS, A DESIGNED 486 00:23:43,120 --> 00:23:44,560 STUDY FROM OUR SCHOOL OF PUBLIC 487 00:23:44,560 --> 00:23:45,120 HEALTH. 488 00:23:45,120 --> 00:23:46,640 WHAT YOU CAN SEE AGAIN IS THREE 489 00:23:46,640 --> 00:23:50,480 DOSES OF BioNTech AND THREE 490 00:23:50,480 --> 00:23:52,920 DOSES OF CORONAVAC AND THIS IS 491 00:23:52,920 --> 00:23:54,560 AGAINST ANY INFECTION BECAUSE 492 00:23:54,560 --> 00:23:56,960 THIS WOULD DETECT NOT JUST 493 00:23:56,960 --> 00:24:00,880 SYMPTOMATIC INFECTION BUT ANY 494 00:24:00,880 --> 00:24:02,320 INFECTION, BioNTech IS 495 00:24:02,320 --> 00:24:03,760 BETTER THAN CORONAVAC BUT NOT BY 496 00:24:03,760 --> 00:24:04,080 MUCH. 497 00:24:04,080 --> 00:24:08,440 AGAIN IF YOU JUST LOOK AT THE 498 00:24:08,440 --> 00:24:09,320 NEUTRALIZATION DIFFERENCE, YOU 499 00:24:09,320 --> 00:24:10,720 SEE THIS HUGE DIFFERENCE BETWEEN 500 00:24:10,720 --> 00:24:11,840 THE TWO. 501 00:24:11,840 --> 00:24:13,920 SO YOU WOULD EXPECT A MUCH 502 00:24:13,920 --> 00:24:17,960 BIGGER DIFFERENCE IN VACCINE 503 00:24:17,960 --> 00:24:18,840 EFFECTIVENESS. 504 00:24:18,840 --> 00:24:23,440 A THIRD STUDY BASED ON 505 00:24:23,440 --> 00:24:25,200 POPULATION-BASED SEROLOGY 506 00:24:25,200 --> 00:24:27,040 COHORT, AGAIN COMES TO SIMILAR 507 00:24:27,040 --> 00:24:27,920 CONCLUSION. 508 00:24:27,920 --> 00:24:29,480 BOTH VACCINES WERE PROVIDING 509 00:24:29,480 --> 00:24:32,520 THREE DOSES OF EITHER VACCINE 510 00:24:32,520 --> 00:24:34,400 WAS PROVIDING SOME PROTECTION, 511 00:24:34,400 --> 00:24:37,280 AND IN THIS CASE IT IS AGAINST 512 00:24:37,280 --> 00:24:41,640 ANY FORM OF INFECTION AT ALL. 513 00:24:41,640 --> 00:24:45,040 NOT JUST SYMPTOMATIC OR SEVERE 514 00:24:45,040 --> 00:24:45,360 INFECTION. 515 00:24:45,360 --> 00:24:47,880 SO, OF COURSE WE WANTED TO LOOK 516 00:24:47,880 --> 00:24:51,920 AT T CELLS BECAUSE THAT ONE 517 00:24:51,920 --> 00:24:52,480 WOULD EXPECT BROADER 518 00:24:52,480 --> 00:24:53,440 CROSS-REACTIVITY, AND THESE ARE 519 00:24:53,440 --> 00:24:55,760 THE COHORTS THAT WE USE, AND 520 00:24:55,760 --> 00:24:58,920 JUST TO QUICKLY GO THROUGH THAT, 521 00:24:58,920 --> 00:25:02,640 WHAT YOU HAVE HERE IS THAT IN 522 00:25:02,640 --> 00:25:07,320 TERMS OF CD4 RESPONSES, BOTH 523 00:25:07,320 --> 00:25:14,880 VACCINES DO PROVIDE A RESPONSE 524 00:25:14,880 --> 00:25:16,120 TO SPIKE OVERLAPPING PEPTIDES, 525 00:25:16,120 --> 00:25:18,720 THERE'S A CD8 RESPONSE WITH 526 00:25:18,720 --> 00:25:20,720 BioNTech BUT NOT 527 00:25:20,720 --> 00:25:24,000 SIGNIFICANTLY SO WITH CORONAVAC. 528 00:25:24,000 --> 00:25:25,400 AND VERY IMPORTANTLY, THERE WAS 529 00:25:25,400 --> 00:25:29,240 NO MARKED DIFFERENCE BETWEEN THE 530 00:25:29,240 --> 00:25:32,080 T-CELL RESPONSES TO THE WILDTYPE 531 00:25:32,080 --> 00:25:34,720 SPIKE PEPTIDES OR OMICRON SPIKE 532 00:25:34,720 --> 00:25:35,240 PEPTIDES. 533 00:25:35,240 --> 00:25:39,840 AND IF YOU LOOK, ALTHOUGH BOTH 534 00:25:39,840 --> 00:25:42,680 VACCINES WERE PROVIDING FAIRLY 535 00:25:42,680 --> 00:25:45,480 CLEAR T-CELL RESPONSES, TO 536 00:25:45,480 --> 00:25:50,480 OMICRON, THE RNA VACCINE WAS 537 00:25:50,480 --> 00:25:52,240 SIGNIFICANTLY HIGHER. 538 00:25:52,240 --> 00:25:54,640 NOW, SINCE THE INACTIVATED 539 00:25:54,640 --> 00:25:55,600 VACCINE CONTAINS MULTIPLE 540 00:25:55,600 --> 00:25:57,040 PEPTIDES, OR MULTIPLE PROTEINS, 541 00:25:57,040 --> 00:25:59,000 NOT JUST SPIKE, WE ALSO LOOKED 542 00:25:59,000 --> 00:26:02,720 AT THE POOL OF OVERLAPPING 543 00:26:02,720 --> 00:26:04,920 PEPTIDES INCLUDING MMNE AND 544 00:26:04,920 --> 00:26:05,880 ESSENTIALLY RESULTS WERE 545 00:26:05,880 --> 00:26:11,480 ESSENTIALLY THE SAME. 546 00:26:11,480 --> 00:26:16,960 SO, RESPONSES TO CD8, TO BOTH 547 00:26:16,960 --> 00:26:18,280 WILDTYPE AND OMICRON AT QUITE A 548 00:26:18,280 --> 00:26:18,680 SUBSTANTIAL LEVEL. 549 00:26:18,680 --> 00:26:21,200 AND THEN IF YOU FOLLOW THESE 550 00:26:21,200 --> 00:26:24,360 PATIENTS UP, YOU SEE THAT AFTER 551 00:26:24,360 --> 00:26:27,920 TWO DOSES, AND THEN AFTER SOME 552 00:26:27,920 --> 00:26:29,240 MONTHS, THERE'S SOME REDUCTION 553 00:26:29,240 --> 00:26:32,760 IN THE T-CELL RESPONSES, AND A 554 00:26:32,760 --> 00:26:33,880 BOOSTER WILL BRING THIS BACK TO 555 00:26:33,880 --> 00:26:35,760 MORE OR LESS THE SAME LEVELS AS 556 00:26:35,760 --> 00:26:37,440 WAS FOUND AFTER THE TWO DOSES. 557 00:26:37,440 --> 00:26:40,200 IT DOESN'T SEEM TO GO MUCH 558 00:26:40,200 --> 00:26:42,600 HIGHER BUT IT JUST REVERSES THE 559 00:26:42,600 --> 00:26:43,800 WAITING THAT YOU SEE. 560 00:26:43,800 --> 00:26:48,800 AND THIS WAS TRUE FOR CD4 AND 561 00:26:48,800 --> 00:26:53,480 CD8 RESPONSES. 562 00:26:53,480 --> 00:26:55,280 AND BOTH VACCINES INDUCE THE 563 00:26:55,280 --> 00:26:56,240 PARTICULARLY T CELL EFFECTOR 564 00:26:56,240 --> 00:26:58,000 MEMORY. 565 00:26:58,000 --> 00:27:00,160 IF I JUST SUMMARIZE THIS PART OF 566 00:27:00,160 --> 00:27:10,800 IT, IN TERMS OF INUST NEUTRALIG 567 00:27:10,800 --> 00:27:11,960 ANTIBODY, COMPARED TO 568 00:27:11,960 --> 00:27:13,440 INACTIVATED VACCINE, THREE DOSES 569 00:27:13,440 --> 00:27:17,200 OF THE RNA VACCINE ELICITED GOOD 570 00:27:17,200 --> 00:27:18,040 CROSS-NEUTRALIZING ANTIBODY TO 571 00:27:18,040 --> 00:27:20,360 VARIANTS SUCH AS OMICRON, TWO 572 00:27:20,360 --> 00:27:24,000 DOSES OF CORONAVAC WITH RNA 573 00:27:24,000 --> 00:27:26,360 BOOSTER ELICITED A GOOD 574 00:27:26,360 --> 00:27:28,480 NEUTRALIZING ANTIBODY TO 575 00:27:28,480 --> 00:27:29,080 VARIANTS. 576 00:27:29,080 --> 00:27:30,640 HOWEVER, MULTIPLE FIELD STUDIES 577 00:27:30,640 --> 00:27:32,840 SUGGESTED THAT THREE DOSES OF 578 00:27:32,840 --> 00:27:35,240 EITHER VACCINE PROTECTS WELL 579 00:27:35,240 --> 00:27:37,640 FROM SEVERE DISEASE AND NOT 580 00:27:37,640 --> 00:27:40,480 GREATLY -- AND LEAVING ASIDE 581 00:27:40,480 --> 00:27:42,800 SEVERE DISEASE, THE VACCINE 582 00:27:42,800 --> 00:27:46,520 EFFECTIVENESS WAS NOT MARKEDLY 583 00:27:46,520 --> 00:27:49,440 DISSIMILAR EVEN FROM INFECTION. 584 00:27:49,440 --> 00:27:51,240 ALTHOUGH, AGAIN, AT THE 585 00:27:51,240 --> 00:27:52,240 NEUTRALIZING ANTIBODY LEVEL, 586 00:27:52,240 --> 00:27:54,520 THERE WAS A STARK DIFFERENCE 587 00:27:54,520 --> 00:27:57,920 BETWEEN THE TWO VACCINES. 588 00:27:57,920 --> 00:27:59,320 NOW BOTH VACCINES ELICITED 589 00:27:59,320 --> 00:28:00,440 T-CELL RESPONSES TO ANCESTRAL 590 00:28:00,440 --> 00:28:07,840 VIRUS AND TO THE OMICRON BA.1. 591 00:28:07,840 --> 00:28:10,160 BUT CORONAVAC ELICITS ALSO 592 00:28:10,160 --> 00:28:16,480 ANTIBODIES TO N, WHICH MAY 593 00:28:16,480 --> 00:28:18,240 CONTRIBUTE TO PROTECTION, SO WE 594 00:28:18,240 --> 00:28:20,400 NEED TO BETTER UNDERSTAND THE 595 00:28:20,400 --> 00:28:21,400 CORRELATES OF PROTECTION IS FROM 596 00:28:21,400 --> 00:28:24,840 SEVERE DISEASE OR EVEN FROM 597 00:28:24,840 --> 00:28:26,680 INFECTION, ASSOCIATED WITH 598 00:28:26,680 --> 00:28:27,640 INACTIVATED VACCINES, AT LEAST, 599 00:28:27,640 --> 00:28:33,320 BECAUSE IT APPEARS THAT THE 600 00:28:33,320 --> 00:28:34,680 INACTIVATED VACCINES ARE 601 00:28:34,680 --> 00:28:36,440 OPERATING THROUGH PROTECTIVE 602 00:28:36,440 --> 00:28:37,840 MECHANISMS WHICH CANNOT BE 603 00:28:37,840 --> 00:28:41,000 MEASURED COMPLETELY OR CAPTURED 604 00:28:41,000 --> 00:28:42,920 COMPLETELY BY NEUTRALIZING 605 00:28:42,920 --> 00:28:43,160 ANTIBODY. 606 00:28:43,160 --> 00:28:49,680 AS I SAID IN TERMS OF THE BROAD 607 00:28:49,680 --> 00:28:53,480 PROTECTION, IN PRIMED 608 00:28:53,480 --> 00:29:02,400 INDIVIDUALS ELICITS BROAD 609 00:29:02,400 --> 00:29:03,280 NEUTRALIZING ANTIBODY, ANOTHER 610 00:29:03,280 --> 00:29:05,320 RANDOMIZED COHORT, WE HAD PEOPLE 611 00:29:05,320 --> 00:29:08,480 WHO HAD BEEN VACCINATED WITH 612 00:29:08,480 --> 00:29:10,600 CORONAVAC OR BioNTech, FOR 613 00:29:10,600 --> 00:29:12,760 TWO DOSES, THEN RANDOMIZED TO 614 00:29:12,760 --> 00:29:14,640 RECEIVE EITHER THIRD DOSE OF 615 00:29:14,640 --> 00:29:16,920 CORONAVAC OR THIRD DOSE OF 616 00:29:16,920 --> 00:29:19,560 BioNTech. 617 00:29:19,560 --> 00:29:21,760 THOSE WHO HAD BioNTech 618 00:29:21,760 --> 00:29:23,840 RANDOMIZED TO RECEIVE A THIRD 619 00:29:23,840 --> 00:29:30,000 DOSE OF BioNTech OR 620 00:29:30,000 --> 00:29:33,960 CORONAVAC. 621 00:29:33,960 --> 00:29:37,280 BLOOD SAMPLES WERE COLLECTED. 622 00:29:37,280 --> 00:29:42,000 OMICRON WAVE HIT IN BETWEEN 623 00:29:42,000 --> 00:29:44,200 THESE TWO BLOOD COLLECTIONS. 624 00:29:44,200 --> 00:29:49,880 IT SHOWS THE NUMBERS AND 625 00:29:49,880 --> 00:29:53,360 RANDOMIZATION, THEN A SMALLER 626 00:29:53,360 --> 00:29:56,640 SUBSET WHICH WE TOOK FOR MORE 627 00:29:56,640 --> 00:30:01,800 DETAILS STUDY IN TERMS OF BLOOD 628 00:30:01,800 --> 00:30:06,080 NEUTRALIZING ANTIBODY AND T CELL 629 00:30:06,080 --> 00:30:07,040 RESPONSES. 630 00:30:07,040 --> 00:30:08,440 SIDE EFFECTS WERE COMPARISON, 631 00:30:08,440 --> 00:30:12,000 RNA VACCINES SLIGHTLY MORE SIDE 632 00:30:12,000 --> 00:30:13,960 EFFECTS, SUCH AS FEVER, ACHES, 633 00:30:13,960 --> 00:30:18,200 PAINS, CHILLS, AS ONE WOULD 634 00:30:18,200 --> 00:30:18,600 EXPECT. 635 00:30:18,600 --> 00:30:28,600 THIS AGAIN FROM THIS COHORT, 636 00:30:28,600 --> 00:30:31,360 SAME PATTERN OF INACTIVED, THOSE 637 00:30:31,360 --> 00:30:37,240 WHO HAD TWO DOSES OF 638 00:30:37,240 --> 00:30:39,000 BioNTech AND A DOSE OF 639 00:30:39,000 --> 00:30:40,520 CORONACAV, IT DOESN'T SEEM TO BE 640 00:30:40,520 --> 00:30:51,080 THE NUMBER BECAUSE THE CORONAVAC 641 00:30:56,920 --> 00:30:57,280 BOOSTER 642 00:30:57,280 --> 00:31:02,560 AGAIN AS BASED ON THIS ONE WOULD 643 00:31:02,560 --> 00:31:06,360 EXPECT THREE-DOSE CORONACAV AND 644 00:31:06,360 --> 00:31:07,920 TWO DOSE BioNTech WITH 645 00:31:07,920 --> 00:31:09,640 CORONAVAC BOOSTER TO HAVE POOR 646 00:31:09,640 --> 00:31:12,000 VACCINE EFFECTIVENESS. 647 00:31:12,000 --> 00:31:17,440 THIS COHORT WENT THROUGH THE BIG 648 00:31:17,440 --> 00:31:22,480 FIRST REAL BIG WAVE. 649 00:31:22,480 --> 00:31:27,120 IN THAT COHORT 58 SARS 650 00:31:27,120 --> 00:31:28,000 CORONAVIRUS IDENTIFIED WITHIN 4 651 00:31:28,000 --> 00:31:31,200 TO 6 MONTHS OF POST-BOOSTER, 652 00:31:31,200 --> 00:31:34,280 BOTTOM LINE THE VACCINE 653 00:31:34,280 --> 00:31:38,200 EFFECTIVENESS WAS NOT MARKEDLY 654 00:31:38,200 --> 00:31:38,560 DIFFERENT. 655 00:31:38,560 --> 00:31:42,480 SO AGAIN THE SAME STORY, THAT 656 00:31:42,480 --> 00:31:45,080 THE NEUTRALIZING ANTIBODY 657 00:31:45,080 --> 00:31:48,840 RESPONSES DID NOT REALLY PREDICT 658 00:31:48,840 --> 00:31:53,720 OBSERVED VACCINE EFFECTIVENESS. 659 00:31:53,720 --> 00:31:55,600 LOOKING AT THESE ANTIBODIES 660 00:31:55,600 --> 00:31:57,560 MEDIATING, AND ALSO ANTIBODY 661 00:31:57,560 --> 00:32:00,520 AVIDITY AND T CELL RESPONSES IN 662 00:32:00,520 --> 00:32:02,080 THESE COHORTS THESE ARE THE -- 663 00:32:02,080 --> 00:32:07,640 THIS IS THE IgB TO ANCESTRAL 664 00:32:07,640 --> 00:32:11,560 AND BA.2 SPOKE, AS EXPECTED. 665 00:32:11,560 --> 00:32:14,000 WE HAVE THE BioNTech BOOSTER 666 00:32:14,000 --> 00:32:17,680 DOING BETTER BUT EVEN THOSE WHO 667 00:32:17,680 --> 00:32:21,720 HAD CORONAVAC DO HAVE SOME 668 00:32:21,720 --> 00:32:23,240 RESPONSE TO OMICRON BA.2 669 00:32:23,240 --> 00:32:26,480 ALTHOUGH AT LOWER LEVEL. 670 00:32:26,480 --> 00:32:27,880 AGAIN, A MUCH MARKEDLY -- WELL, 671 00:32:27,880 --> 00:32:34,920 A SMALLER DIFFERENCE THAN WITH 672 00:32:34,920 --> 00:32:35,280 NEUTRALIZATION. 673 00:32:35,280 --> 00:32:41,680 RIGHT, SO IF YOU LOOK AT THE 674 00:32:41,680 --> 00:32:43,080 ADCC AND ADCP MEDIATING 675 00:32:43,080 --> 00:32:44,400 ANTIBODIES, THESE WERE THE 676 00:32:44,400 --> 00:32:50,200 RESPONSES IN THESE COHORTS TO 677 00:32:50,200 --> 00:32:51,200 BA.2 WHERE BioNTech BOOSED 678 00:32:51,200 --> 00:32:55,120 ONES HAD HIGHEST ANTIBODY 679 00:32:55,120 --> 00:32:57,520 RESPONSES BUT CORONAVAC GROUPS 680 00:32:57,520 --> 00:32:58,760 HAD SOME DETECTABLE RESPONSES 681 00:32:58,760 --> 00:33:03,880 AND WE DON'T KNOW WHAT CORRELATE 682 00:33:03,880 --> 00:33:05,320 OF PROTECTION, IF ANY, THESE 683 00:33:05,320 --> 00:33:05,520 CARRY. 684 00:33:05,520 --> 00:33:14,280 AND THIS IS THE SAME FOR THE FC 685 00:33:14,280 --> 00:33:15,120 RECEPTOR 2A ANTIBODIES. 686 00:33:15,120 --> 00:33:20,600 IN TERMS OF ANTIBODY AVIDITY, IF 687 00:33:20,600 --> 00:33:24,240 YOU LOOK AT ANTIBODY AVIDITY, 688 00:33:24,240 --> 00:33:27,440 AGAIN IT FOLLOWS THAT THE 689 00:33:27,440 --> 00:33:30,600 BioNTech BOOSTER GROUP HAVE 690 00:33:30,600 --> 00:33:35,640 HIGHER ANTIBODY AVIDITY THAN 691 00:33:35,640 --> 00:33:36,920 CORONAVIRUS BOOSTED GROUP 692 00:33:36,920 --> 00:33:40,240 CERTAINLY TO OMICRON. 693 00:33:40,240 --> 00:33:42,320 SINCE ACTIVATED FOLLICULAR T 694 00:33:42,320 --> 00:33:45,480 HELPER CELLS HELP B CELLS TO 695 00:33:45,480 --> 00:33:47,000 FORM TERMINAL CENTERS AND 696 00:33:47,000 --> 00:33:49,200 DRIVE -- BELIEVED TO DRIVE 697 00:33:49,200 --> 00:33:52,720 AVIDITY ANTIBODY RESPONSES WHAT 698 00:33:52,720 --> 00:33:56,240 YOU SEE HERE IS THE TFH 699 00:33:56,240 --> 00:33:57,880 RESPONSES TO THE THREE VACCINES, 700 00:33:57,880 --> 00:34:03,920 THIS IS NOT ANTIGEN SPECIFIC 701 00:34:03,920 --> 00:34:04,880 RESPONSES BUT OVERALL RESPONSES 702 00:34:04,880 --> 00:34:07,960 IN 7th DAY AFTER THE VACCINE, 703 00:34:07,960 --> 00:34:10,680 CAN YOU SEE CC-B GROUP HAS A 704 00:34:10,680 --> 00:34:13,760 VERY GOOD RESPONSE HERE AND BB-B 705 00:34:13,760 --> 00:34:15,320 GROUP HAS ALSO A REASONABLE 706 00:34:15,320 --> 00:34:15,600 RESPONSE. 707 00:34:15,600 --> 00:34:19,360 OVERALL IT SEEMS THAT THE 708 00:34:19,360 --> 00:34:22,560 ANTIBODY AVIDITY DOES CORRELATE 709 00:34:22,560 --> 00:34:28,000 WITH THIS TFH CELL RESPONSE THAT 710 00:34:28,000 --> 00:34:28,560 WE OBSERVED. 711 00:34:28,560 --> 00:34:31,040 THE N ANTIBODY BINDING IS SEEN 712 00:34:31,040 --> 00:34:35,840 HERE AS I SAID, IT'S ONLY THOSE 713 00:34:35,840 --> 00:34:40,040 WHO HAD CORONACAV AND BOOSTED BY 714 00:34:40,040 --> 00:34:42,280 CORONAVAC, INACTIVATED VACCINE 715 00:34:42,280 --> 00:34:45,040 BOOSTER WHO HAVE DETECTABLE 716 00:34:45,040 --> 00:34:48,440 ANTIBODY TITERS TO BINDING 717 00:34:48,440 --> 00:34:52,360 ASSAYS IN AVIDITY SAYS IN ADCC 718 00:34:52,360 --> 00:34:59,400 AND ADCP ANTIBODY ASSAYS AS 719 00:34:59,400 --> 00:34:59,600 WELL. 720 00:34:59,600 --> 00:35:01,720 NOW, IN ANTIBODIES, OF COURSE 721 00:35:01,720 --> 00:35:05,360 ARE NOT -- N ANTIBODIES ARE NOT 722 00:35:05,360 --> 00:35:09,240 THOUGHT ABOUT MUCH IN TERMS OF 723 00:35:09,240 --> 00:35:10,560 PROTECTIVE -- CONFERRING ANY 724 00:35:10,560 --> 00:35:13,640 PROTECTION, BUT THERE WAS THIS 725 00:35:13,640 --> 00:35:17,040 PAPER LAST YEAR WHERE THEY DID 726 00:35:17,040 --> 00:35:19,520 LOOK AT PASSIVE TRANSFER OF N 727 00:35:19,520 --> 00:35:24,720 ANTIBODIES, THIS IS IN A MOUSE 728 00:35:24,720 --> 00:35:27,080 STUDY, AND SHOWED THAT PASSIVE 729 00:35:27,080 --> 00:35:30,040 TRANSFER IN THE MOUSE MODEL DID 730 00:35:30,040 --> 00:35:32,920 LEAD TO REDUCTION IN VIRUS RNA 731 00:35:32,920 --> 00:35:35,400 COPIES IN THE LUNG, AND THEN 732 00:35:35,400 --> 00:35:36,480 THIS IS WITH POLYCLONAL 733 00:35:36,480 --> 00:35:38,920 TRANSFER, AND IF YOU DO THE SAME 734 00:35:38,920 --> 00:35:41,080 PASSIVE TRANSFER USING A 735 00:35:41,080 --> 00:35:43,720 MONOCLONAL ANTIBODY TO N, AGAIN 736 00:35:43,720 --> 00:35:45,600 THEY CAN DEMONSTRATE QUITE 737 00:35:45,600 --> 00:35:47,040 MARKED PROTECTIVE EFFECTS, AND 738 00:35:47,040 --> 00:35:49,880 THEY POSTULATE AND HAVE SHOWN 739 00:35:49,880 --> 00:35:55,720 THAT N PROTEIN IS PRESENT ON THE 740 00:35:55,720 --> 00:35:57,680 CELL -- INFECTED CELL SURFACE 741 00:35:57,680 --> 00:36:00,400 AND CAN MEDIATE ADCC SO ONE CAN 742 00:36:00,400 --> 00:36:05,680 WONDER WHETHER AT LEAST SOME OF 743 00:36:05,680 --> 00:36:07,520 THIS DISCREPANCY BETWEEN THE 744 00:36:07,520 --> 00:36:09,400 INACTIVATED VACCINES AND RNA 745 00:36:09,400 --> 00:36:17,640 VACCINES MAY BE MEDIATED BY N. 746 00:36:17,640 --> 00:36:18,320 T-CELL RESPONSES WERE COMPARABLE 747 00:36:18,320 --> 00:36:20,680 ACROSS THE GROUPS. 748 00:36:20,680 --> 00:36:23,240 THOSE THAT HAD THE BioNTech 749 00:36:23,240 --> 00:36:25,920 BASICALLY HAD MORE T-CELL 750 00:36:25,920 --> 00:36:28,120 RESPONSES TO THE SPIKE PROTEIN, 751 00:36:28,120 --> 00:36:32,040 AND THOSE WHO HAD CC-C, 752 00:36:32,040 --> 00:36:32,720 INACTIVATED VACCINE, HAD MORE 753 00:36:32,720 --> 00:36:34,400 BIAS TOWARDS THE OTHER PEPTIDES 754 00:36:34,400 --> 00:36:36,640 OF THE VIRUS AS ONE WOULD 755 00:36:36,640 --> 00:36:37,880 EXPECT. 756 00:36:37,880 --> 00:36:40,880 IF YOU LOOK AT T CELL QUALITY, 757 00:36:40,880 --> 00:36:42,680 ASSESSED BY POLY FUNCTIONALITY, 758 00:36:42,680 --> 00:36:52,040 IN TERMS OF MULTIPLE CYTOKINE 2, 759 00:36:52,040 --> 00:36:54,960 SHOWN HERE IN THE PEPTIDE POOLS, 760 00:36:54,960 --> 00:36:58,040 YOU CAN SEE THIS INACTIVATED 761 00:36:58,040 --> 00:36:59,920 VACCINE GROUP DOES SEEM TO HAVE 762 00:36:59,920 --> 00:37:05,280 A TREND TO HAVE STRONGER 763 00:37:05,280 --> 00:37:07,240 POLYFUNCTIONAL T-CELL RESPONSE. 764 00:37:07,240 --> 00:37:11,080 SO, JUST TO CONCLUDE THAT 765 00:37:11,080 --> 00:37:12,600 PARTICULAR STUDY, ESSENTIALLY 766 00:37:12,600 --> 00:37:14,200 WHAT WE SEE WAS THAT LOOKING AT 767 00:37:14,200 --> 00:37:17,720 THE FOUR ARMS OF THE RESPONSE, 768 00:37:17,720 --> 00:37:28,080 IN TERMS OF SPIKE IgG, 769 00:37:29,920 --> 00:37:34,360 NEUTRALIZATION, AND AVIDITY, 770 00:37:34,360 --> 00:37:44,800 C.C.-C AND CC-B HAVE THE 771 00:37:49,880 --> 00:37:50,080 RESPONSES. 772 00:37:50,080 --> 00:37:52,520 IN TERMS OF T CELLS, THEY ARE 773 00:37:52,520 --> 00:37:53,520 MORE OR LESS COMPARABLE ACROSS 774 00:37:53,520 --> 00:37:55,680 THE GROUPS. 775 00:37:55,680 --> 00:38:04,040 IN TERMS OF THE POLYFUNCTIONAL 776 00:38:04,040 --> 00:38:06,080 RESPONSES IT IS BEST IN -- 777 00:38:06,080 --> 00:38:07,880 CERTAINLY IN TERMS OF THE 778 00:38:07,880 --> 00:38:12,120 MULTIPLE PEPTIDES, IT IS BETTER 779 00:38:12,120 --> 00:38:15,600 IN THE CORONAVAC GROUP. 780 00:38:15,600 --> 00:38:16,920 TO SUMMARIZE ESSENTIALLY LASTING 781 00:38:16,920 --> 00:38:21,400 AND QUALITY T CELLS AGAINST THE 782 00:38:21,400 --> 00:38:26,240 SPIKE AND NEM, AND ANTIBODY 783 00:38:26,240 --> 00:38:28,840 RESPONSES IN CORONAVAC PRIMED 784 00:38:28,840 --> 00:38:30,400 DONORS MAY BE IMPORTANT SO I 785 00:38:30,400 --> 00:38:32,800 THINK WE DO NEED A BETTER 786 00:38:32,800 --> 00:38:35,280 UNDERSTANDING OF THE CORRELATES 787 00:38:35,280 --> 00:38:39,040 OF PROTECTION OF INACTIVATED 788 00:38:39,040 --> 00:38:40,680 VACCINES BECAUSE THE 789 00:38:40,680 --> 00:38:43,920 NEUTRALIZING DATA CERTAINLY DOES 790 00:38:43,920 --> 00:38:46,760 NOT RECORD WITH WHAT WE OBSERVED 791 00:38:46,760 --> 00:38:47,960 IN VACCINE EFFECTIVENESS 792 00:38:47,960 --> 00:38:49,440 STUDIES. 793 00:38:49,440 --> 00:38:52,000 AS I MENTIONED, PRIMING WITH 794 00:38:52,000 --> 00:38:54,800 SARS CORONAVIRUS 1 LEADS TO 795 00:38:54,800 --> 00:38:56,840 BROAD CROSS-PROTECTION, THIS MAY 796 00:38:56,840 --> 00:39:02,000 BE RELEVANT TO BROADLY 797 00:39:02,000 --> 00:39:02,920 CROSS-PROTECTIVE VACCINES. 798 00:39:02,920 --> 00:39:04,320 I WILL END. 799 00:39:04,320 --> 00:39:05,480 I'VE GIVEN MY ACKNOWLEDGMENTS. 800 00:39:05,480 --> 00:39:14,920 AND I'LL BE HAPPY TO TAKE ANY 801 00:39:14,920 --> 00:39:15,360 QUESTIONS. 802 00:39:15,360 --> 00:39:16,000 THANK YOU. 803 00:39:16,000 --> 00:39:17,120 >> THANK YOU, MALIK, FOR THIS 804 00:39:17,120 --> 00:39:18,360 LOVELY TALK. 805 00:39:18,360 --> 00:39:21,920 WE HAVE A FEW QUESTIONS. 806 00:39:21,920 --> 00:39:28,000 HOW DOES THIS DATA WITH THE 807 00:39:28,000 --> 00:39:32,560 CORONAVAC COMPARE TO ASTRAZENECA 808 00:39:32,560 --> 00:39:33,000 VACCINE OR NOVAVAX? 809 00:39:33,000 --> 00:39:33,760 >> RIGHT. 810 00:39:33,760 --> 00:39:36,720 SO I CANNOT REALLY COMMENT ON 811 00:39:36,720 --> 00:39:38,040 THAT BECAUSE WE REALLY DIDN'T 812 00:39:38,040 --> 00:39:39,240 USE ANY OF THOSE VACCINES IN 813 00:39:39,240 --> 00:39:42,840 HONG KONG. 814 00:39:42,840 --> 00:39:48,840 WE DON'T HAVE DATA OURSELVES. 815 00:39:48,840 --> 00:39:51,200 WE HAVE SOME RETURNING TRAVELERS 816 00:39:51,200 --> 00:39:57,720 VACCINATED WITH THESE BUT NOT 817 00:39:57,720 --> 00:39:59,800 ENOUGH FOR STUDIES, WE CAN'T 818 00:39:59,800 --> 00:40:04,000 COMMENT ON ADENOVIRUS OR PROTEIN 819 00:40:04,000 --> 00:40:04,240 VACCINES. 820 00:40:04,240 --> 00:40:04,720 >> OKAY. 821 00:40:04,720 --> 00:40:07,640 AND SO LET'S SEE. 822 00:40:07,640 --> 00:40:08,520 QUITE A FEW QUESTIONS. 823 00:40:08,520 --> 00:40:12,000 >> SO I THINK JUST ONE THING 824 00:40:12,000 --> 00:40:14,680 REGARDING THE ADENOVIRUS VECTOR 825 00:40:14,680 --> 00:40:21,160 VACCINES OR ASTRAZENECA, ONE 826 00:40:21,160 --> 00:40:23,120 POINT, AT A RECENT MEETING ON 827 00:40:23,120 --> 00:40:25,640 THIS, IT WAS POINTED OUT THAT IN 828 00:40:25,640 --> 00:40:28,560 THE U.K. AS YOU REMEMBER THEY 829 00:40:28,560 --> 00:40:30,160 GAVE SINGLE DOSE AND THEY DID 830 00:40:30,160 --> 00:40:32,880 NOT GIVE THE SECOND DOSE BECAUSE 831 00:40:32,880 --> 00:40:34,000 OF INITIAL SHORTAGE OF VACCINE 832 00:40:34,000 --> 00:40:34,400 SUPPLY. 833 00:40:34,400 --> 00:40:36,800 BUT AS SHE POINTED OUT, THAT 834 00:40:36,800 --> 00:40:40,240 SINGLE DOSE DID SEEM TO CONFER 835 00:40:40,240 --> 00:40:41,640 SOMETHING LIKE 70% VACCINE 836 00:40:41,640 --> 00:40:42,840 EFFECTIVENESS OVER THE PERIOD OF 837 00:40:42,840 --> 00:40:45,880 ABOUT FOUR OR FIVE MONTHS, AS 838 00:40:45,880 --> 00:40:47,520 SHE SAYS, THIS WAS IN THE 839 00:40:47,520 --> 00:40:49,920 ABSENCE IN THAT VACCINE IN THE 840 00:40:49,920 --> 00:40:55,880 ABSENCE OF ANY DETECTABLE OR 841 00:40:55,880 --> 00:40:57,920 SIGNIFICANT NEUTRALIZING 842 00:40:57,920 --> 00:41:00,760 ANTIBODY RESPONSES. 843 00:41:00,760 --> 00:41:09,080 THERE ARE SOME DISCREPANCIES IN 844 00:41:09,080 --> 00:41:10,040 HOW VACCINES PROTECT. 845 00:41:10,040 --> 00:41:12,560 >> SINCE AGING CAN PLAY A ROLE 846 00:41:12,560 --> 00:41:14,680 IN ANTIBODY AVIDITY DO YOU SEE 847 00:41:14,680 --> 00:41:17,640 DIFFERENCES IN ANTIBODY AVIDITY 848 00:41:17,640 --> 00:41:22,200 BETWEEN DIFFERENT AGE GROUPS, 849 00:41:22,200 --> 00:41:23,200 BETWEEN THE INACTIVATED 850 00:41:23,200 --> 00:41:24,720 CORONAVAC VAC AND mRNA 851 00:41:24,720 --> 00:41:24,960 VACCINE? 852 00:41:24,960 --> 00:41:30,000 >> YEAH, SO I MEAN WE DON'T HAVE 853 00:41:30,000 --> 00:41:34,160 ENOUGH NUMBERS THAT WE'VE DONE 854 00:41:34,160 --> 00:41:39,520 AVIDITY STUDIES ON, TO 855 00:41:39,520 --> 00:41:41,040 CONFIDENTLY SHOW AGE-RELATED 856 00:41:41,040 --> 00:41:43,600 EFFECTS, BUT I DO TAKE YOUR 857 00:41:43,600 --> 00:41:48,280 POINT ABOUT THE ROLE OF AGING IN 858 00:41:48,280 --> 00:41:50,800 THESE ANTIBODY RESPONSES. 859 00:41:50,800 --> 00:41:51,160 YEAH, UH-HUH. 860 00:41:51,160 --> 00:41:53,080 >> SURRENDER HAS A QUESTION. 861 00:41:53,080 --> 00:41:55,920 ANY AGE DIFFERENCES ALSO FOR 862 00:41:55,920 --> 00:42:00,200 ADCC OR ADCP ACTIVITY BETWEEN 863 00:42:00,200 --> 00:42:00,960 mRNA VERSUS INACTIVATED 864 00:42:00,960 --> 00:42:01,240 VACCINES? 865 00:42:01,240 --> 00:42:02,720 >> YEAH, SO WE HAVE THE SAME 866 00:42:02,720 --> 00:42:05,560 PROBLEM IN THE NUMBERS THAT WE 867 00:42:05,560 --> 00:42:05,720 USE. 868 00:42:05,720 --> 00:42:07,440 WE USED AGE-MATCHED GROUPS BUT 869 00:42:07,440 --> 00:42:09,320 THE NUMBERS WERE NOT SUFFICIENT 870 00:42:09,320 --> 00:42:14,200 FOR US TO LOOK AT THE IMPACT OF 871 00:42:14,200 --> 00:42:18,520 AGE ON THE RESPONSES PER SE. 872 00:42:18,520 --> 00:42:20,000 >> GENERAL QUESTION, SO GIVEN 873 00:42:20,000 --> 00:42:23,920 WHAT YOU'VE SHOWN US TODAY, IT 874 00:42:23,920 --> 00:42:27,240 SOUNDS LIKE T-CELL RESPONSES ARE 875 00:42:27,240 --> 00:42:32,160 A BETTER GAUGE OF LONG-TERM 876 00:42:32,160 --> 00:42:33,040 PROTECTION THAN NEUTRALIZING 877 00:42:33,040 --> 00:42:33,440 TITERS. 878 00:42:33,440 --> 00:42:35,120 IS THAT HOW YOU WOULD SORT OF 879 00:42:35,120 --> 00:42:39,160 FRAME IT BASED ON WHAT YOU'VE 880 00:42:39,160 --> 00:42:39,400 LEARNED? 881 00:42:39,400 --> 00:42:43,840 >> WELL, I WOULD SAY THAT AT 882 00:42:43,840 --> 00:42:45,400 LEAST FOR THE INACTIVATED 883 00:42:45,400 --> 00:42:46,800 VACCINES, I DON'T THINK 884 00:42:46,800 --> 00:42:48,920 NEUTRALIZING ANTIBODY IS TELLING 885 00:42:48,920 --> 00:42:50,600 US THE WHOLE STORY. 886 00:42:50,600 --> 00:42:53,160 NOW, THAT MAY ALSO BE TRUE FOR 887 00:42:53,160 --> 00:42:54,680 THE OTHER VACCINES, BUT TO A 888 00:42:54,680 --> 00:42:55,800 LESSER EXTENT. 889 00:42:55,800 --> 00:42:57,200 I MEAN, IN OTHER STUDIES DONE BY 890 00:42:57,200 --> 00:43:01,680 A NUMBER OF STUDIES, I MEAN, 891 00:43:01,680 --> 00:43:08,520 ONES DONE BY THE AUSTRALIAN 892 00:43:08,520 --> 00:43:10,120 GROUP, MILES DAVENPORT AND 893 00:43:10,120 --> 00:43:11,960 OTHERS, THEY FOUND CLEAR 894 00:43:11,960 --> 00:43:14,480 CORRELATION IN PUBLISHED 895 00:43:14,480 --> 00:43:16,360 CLINICAL TRIALS, CLEAR 896 00:43:16,360 --> 00:43:17,880 CORRELATION BETWEEN NEUTRALIZING 897 00:43:17,880 --> 00:43:19,760 TITERS AND PROTECTION. 898 00:43:19,760 --> 00:43:21,400 THAT SEEMED TO BE A GOOD 899 00:43:21,400 --> 00:43:22,240 CORRELATE OF PROTECTION AND 900 00:43:22,240 --> 00:43:25,200 THAT'S HOW THEY CAME UP WITH 901 00:43:25,200 --> 00:43:25,880 THESE THRESHOLDS. 902 00:43:25,880 --> 00:43:29,560 AND THIS WAS ALSO TRUE FOR 903 00:43:29,560 --> 00:43:33,760 VARIANTS, WHICH THEY DID LATER. 904 00:43:33,760 --> 00:43:41,720 BUT LIKE I SAY, I MEAN, I 905 00:43:41,720 --> 00:43:44,360 WOULDN'T COMPLETELY DISMISS IS 906 00:43:44,360 --> 00:43:46,600 NEUTRALIZING ANTIBODY FOR RNA 907 00:43:46,600 --> 00:43:54,760 VACCINES, FOR THE ADENOVIRUS 908 00:43:54,760 --> 00:43:56,040 VECTORED VACCINE, CORRELATIVE 909 00:43:56,040 --> 00:43:56,800 EVIDENCE THERE, BUT WHAT I'M 910 00:43:56,800 --> 00:43:58,120 BEGINNING TO THINK AND WHAT MY 911 00:43:58,120 --> 00:43:59,560 COLLEAGUES ARE BEGINNING TO 912 00:43:59,560 --> 00:44:03,720 THINK IS THAT CERTAINLY FOR 913 00:44:03,720 --> 00:44:05,760 INACTIVATED VACCINES THAT IS NOT 914 00:44:05,760 --> 00:44:07,560 THE ONLY PART OF THE STORY. 915 00:44:07,560 --> 00:44:11,480 SO I THINK, YEAH, WE HAVE TO 916 00:44:11,480 --> 00:44:13,680 LOOK WIDER THAN THAT. 917 00:44:13,680 --> 00:44:16,400 >> WHAT IS YOUR VIEW ON 918 00:44:16,400 --> 00:44:19,160 PERSISTENT RESERVOIRS OF THE 919 00:44:19,160 --> 00:44:22,200 VIRUS BEING PRESENT IN THESE 920 00:44:22,200 --> 00:44:23,320 INDIVIDUALS THAT HAVE BEEN -- 921 00:44:23,320 --> 00:44:28,120 THAT COULD BE BOOSTING THE 922 00:44:28,120 --> 00:44:31,720 IMMUNE RESPONSE OVER TIME? 923 00:44:31,720 --> 00:44:33,040 >> WE DON'T REALLY SEE A BOOST 924 00:44:33,040 --> 00:44:36,880 OF IMMUNE RESPONSE OVER TIME, IN 925 00:44:36,880 --> 00:44:38,440 THE ABSENCE OF REPEATED 926 00:44:38,440 --> 00:44:43,760 INFECTION, BECAUSE IN THOSE THAT 927 00:44:43,760 --> 00:44:45,080 WE HAVE FOLLOWED, YOU KNOW, WHAT 928 00:44:45,080 --> 00:44:47,280 WE DO SEE IS WANING ANTIBODY. 929 00:44:47,280 --> 00:44:49,120 OF COURSE THERE MAY BE SOME 930 00:44:49,120 --> 00:44:51,880 INDIVIDUALS WHERE THERE'S VIRUS 931 00:44:51,880 --> 00:45:00,320 PERSISTENCE AND BOOSTING, AFTER 932 00:45:00,320 --> 00:45:01,720 BREAK THROUGH INFECTIONS? 933 00:45:01,720 --> 00:45:02,600 >> AFTER BREAKTHROUGH 934 00:45:02,600 --> 00:45:03,160 INFECTION, YEAH. 935 00:45:03,160 --> 00:45:08,080 >> I KNOW THE DATA ON 936 00:45:08,080 --> 00:45:08,840 PERSISTENCE IN THE 937 00:45:08,840 --> 00:45:09,680 GASTROINTESTINAL TRACT AND 938 00:45:09,680 --> 00:45:11,920 THINGS LIKE THAT, OF COURSE THE 939 00:45:11,920 --> 00:45:14,880 WHOLE STORY ABOUT LONG COVID AND 940 00:45:14,880 --> 00:45:16,960 PROLONGED COMPLICATIONS OF 941 00:45:16,960 --> 00:45:17,480 COVID. 942 00:45:17,480 --> 00:45:20,680 AND BUT I MEAN ESSENTIALLY, WHAT 943 00:45:20,680 --> 00:45:27,400 WE DO SEE IS WANING ANTIBODY, 944 00:45:27,400 --> 00:45:31,520 BUT LIKE I SAY, I CAN'T EXPLORE 945 00:45:31,520 --> 00:45:33,920 THE POSSIBILITY THAT SOME MINOR 946 00:45:33,920 --> 00:45:36,680 SUBPOPULATION DOES HAVE, YOU 947 00:45:36,680 --> 00:45:42,240 KNOW, A BOOST FROM PERSISTENT 948 00:45:42,240 --> 00:45:42,840 VIRUS ACTIVITY. 949 00:45:42,840 --> 00:45:44,320 >> RIGHT. 950 00:45:44,320 --> 00:45:46,640 THERE'S A QUESTION REGARDING 951 00:45:46,640 --> 00:45:48,920 THE -- BASED ON EMERGENTS OF NEW 952 00:45:48,920 --> 00:45:51,760 VARIANTS, WHAT IS THE STRAIN 953 00:45:51,760 --> 00:45:52,880 COMPOSITION FOR VACCINES IN 954 00:45:52,880 --> 00:45:58,440 CONGRESS -- HONG KONG, FOR FAL, 955 00:45:58,440 --> 00:45:59,480 DO YOU HAVE THOUGHTS? 956 00:45:59,480 --> 00:46:03,920 >> PFIZER/BIONTECH, WE SWITCHED 957 00:46:03,920 --> 00:46:10,160 TO BIVALENT WITH ANCESTRAL AND 958 00:46:10,160 --> 00:46:14,080 BA.5, USED CURRENTLY, BUT IF 959 00:46:14,080 --> 00:46:18,760 THERE IS AN UPDATED VACCINE THAT 960 00:46:18,760 --> 00:46:19,760 BECOMES AVAILABLE, CLEARLY HONG 961 00:46:19,760 --> 00:46:20,880 KONG WOULD CONSIDER USING THAT 962 00:46:20,880 --> 00:46:24,120 AS WELL. 963 00:46:24,120 --> 00:46:25,480 NOW, THE INACTIVATED VACCINES 964 00:46:25,480 --> 00:46:30,800 ALSO HAVE -- ARE COMING UP WITH 965 00:46:30,800 --> 00:46:32,040 OMICRON-BASED INACTIVATED 966 00:46:32,040 --> 00:46:33,560 VACCINE BUT I HAVEN'T REALLY 967 00:46:33,560 --> 00:46:36,280 SEEN ANY CLINICAL DATA ON THAT, 968 00:46:36,280 --> 00:46:37,720 SO THAT'S SOMETHING THAT WE 969 00:46:37,720 --> 00:46:39,520 MIGHT ALSO NEED TO CONSIDER. 970 00:46:39,520 --> 00:46:41,440 AND THEN THE OTHER THING ON THE 971 00:46:41,440 --> 00:46:42,520 HORIZON OF COURSE AT LEAST IN 972 00:46:42,520 --> 00:46:45,600 THIS PART OF THE WORLD IS THIS 973 00:46:45,600 --> 00:46:48,000 INTRANASAL VACCINE COMING FROM 974 00:46:48,000 --> 00:46:53,480 MAINLAND CHINA, WHICH IS ADENO5 975 00:46:53,480 --> 00:46:54,120 VECTORED VACCINE GIVEN 976 00:46:54,120 --> 00:46:56,320 INTRANASALLY, ON THE BASIS OF 977 00:46:56,320 --> 00:46:58,520 EARLY CLINICAL TRIALS RESULTS 978 00:46:58,520 --> 00:47:00,040 THAT THEY ARE SHOWING SEEMS 979 00:47:00,040 --> 00:47:04,640 QUITE PROMISING, SEARCH IN TERMS 980 00:47:04,640 --> 00:47:05,960 OF IMMUNOGENICITY, I DON'T THINK 981 00:47:05,960 --> 00:47:08,040 THERE IS GOOD VACCINE 982 00:47:08,040 --> 00:47:09,160 EFFECTIVENESS DATA YET SO THAT'S 983 00:47:09,160 --> 00:47:11,560 ANOTHER THING THAT CERTAINLY WE 984 00:47:11,560 --> 00:47:12,800 WOULD CONSIDER. 985 00:47:12,800 --> 00:47:17,680 >> ANY THOUGHTS ON TRANSMISSION 986 00:47:17,680 --> 00:47:17,960 BLOCKING? 987 00:47:17,960 --> 00:47:19,320 >> CLEARLY THERE'S NO EVIDENCE 988 00:47:19,320 --> 00:47:20,400 OF IT. 989 00:47:20,400 --> 00:47:23,800 IT'S VERY CHALLENGING TO LOOK AT 990 00:47:23,800 --> 00:47:25,320 TRANSMISSION BLOCKING, BUT, 991 00:47:25,320 --> 00:47:26,960 YEAH, CLEARLY THAT WOULD BE -- 992 00:47:26,960 --> 00:47:29,400 YEAH, THAT WOULD BE THE MAJOR 993 00:47:29,400 --> 00:47:32,760 INTEREST IN SUCH A VACCINE 994 00:47:32,760 --> 00:47:34,880 BECAUSE ON THE IMMUNOGENICITY 995 00:47:34,880 --> 00:47:37,040 STUDIES INDUCING GOOD INTRANASAL 996 00:47:37,040 --> 00:47:40,760 IMMUNITY BUT ALSO QUITE 997 00:47:40,760 --> 00:47:43,360 SURPRISINGLY QUITE GOOD SYSTEMIC 998 00:47:43,360 --> 00:47:45,160 ANTIBODY RESPONSES AS WELL, 999 00:47:45,160 --> 00:47:49,440 WHICH IS SURPRISING FOR ME 1000 00:47:49,440 --> 00:47:49,680 ANYWAY. 1001 00:47:49,680 --> 00:47:52,040 >> THANK YOU SO MUCH FOR YOUR 1002 00:47:52,040 --> 00:47:53,240 TALK. 1003 00:47:53,240 --> 00:47:54,240 AND THIS ENDS TODAY'S SEMINAR. 1004 00:47:54,240 --> 00:00:00,000 >> THANK YOU.