>>MY NAME IS STEVE HOLLAND
I'M VERY VOICE CHALLENGED
RIGHT NOW BUT DON'T WANT IT TO
GET IN THE WAY OF TELLING YOU
ABOUT THIS EXTRAORDINARY YOUNG
SCIENTIST THAT I'M REALLY
LOOKING FORWARD TO SHOWING SOME
OF THE WORK THAT VINCENT HAS
DONE. SORRY. I WAS HAVING SOME
TECHNICAL DIFFICULTIES.
DR. MUNSTER IS CURRENTLY THE
CHIEF OF THE VIRUS ECOLOGY UNIT
IN THE LABORATORY OF VIROLOGY AT
ROCKY MOUNTAIN LABS. OF COURSE,
HE DIDN'T START THERE. DR.
MUNSTER COMES FROM THE
NETHERLANDS AND MOST DON'T CARE
MUCH ABOUT THE GEOGRAPHY ABOUT
THE NETHERLANDS BUT IF YOUR NAME
IS HOLLAND YOU CARE ABOUT THE
GEOGRAPHY OF THE NETHERLANDS HE
WENT NOT TO FAR TO ROTTER DAMN
DOING FIRST HIS MASTERS THEN PHD
AND AFTER A PERIOD OF POST
DOCTORAL WORK THERE IN ROTTER
DAMN HE MADE THE BOLD AND FOR US
TREMENDOUSLY FELICITOUS DECISION
TO GO TO MONTANA IN 2009 WHERE
HE STAYED FOR MANY YEARS AND
SINCE 2009 AND HAS BECOME
TENURED IN THE CHIEF OF HIS OWN
SECTION.
OF COURSE, THIS BUG, AS IT WERE,
THAT HAS STARTED HIM TRAVELING
TO MONDAY TANNA HASN'T STOPPED.
HE HAS MANY EXTRAORDINARY
ACTIVITIES IN AFRICA THAT YOU
CAN SEE HERE WITH SITES IN CONGO
AND LIEBERIA ANDGANA AND MALI
AND THERE IS A SITE OPENING IN
UGANDA IN THE NEXT YEAR WHERE I
THINK THAT VINCENT WILL HAVE
LOTS OF ACCESS TO VIEFRUSES IN
THAT ROO EDGEON AND HIS WORK IN
JORDAN AND MIDDLE EAST IN MRS IS
AT THE FOREFRONT IN THE FIELD
AND SETD THE STAGE FOR BEING
ABLE TO TAKE ON MORE MODERN
CORONAVIRUSES NOT TO BE OUTDONE
IN TRAVELS WEST HE HAS ALSO
ENGAGED WORK ON HEN DROE VIRUS
IN AUSTRALIA THAT IS EXTREMELY
SUCCESSFUL AND DON'T TAKE MY
WORD FOR ALL OF THIS IN 2020
ALONG WITH EMI DEWITT VINCENT
WAS THE RECIPIENT OF THE GOLDEN
GOOSE AWARD AND NORMAN SALSMAN
GRADUATE STUDENT AWARD IN BASIC
CLINICAL VIROLOGY AND TO HAVE IT
THAT KIND OF SKILL TO DO BOTH
SCIENCE AND EDUCATION AND FIELD
WORK IS RARE INDEED.
I HAVE TO SAY THAT VINCENT HAD
HIS BSC REVIEW LAST MONTH. I
WAS INJURED IN THE PROCESS SO
WHEN THE BSC GAVE THE REPORT IT
WAS SO GLOWING I GOT SUNBURNED.
IT HAS REALLY CRIPPLED ME A
LITTLE BIT.
IT IS A GREAT PLEASURE TO
INTRODUCE VINCENT MUNSTER TO
YOU. HE HAS DONE A SPECTACULAR
JOB AND KNOW HE WILL SHOW YOU
THAT NOW. THANKS. VINCENT,
TAKE IT AWAY.
>> THANK YOU, STEVE. REALLY
GREAT INTRODUCTION AND THANKING
KENNY KUMAR WHO IS HELPING TO
FACILITATE AND ORGANIZE THIS
ZOOM CAST AND ALSO PUTTING UP A
PICTURE OF PROBABLY MORE THAN 10
YEARS AGO THAT TRICKED DR.
HOLLAND CALLING ME THAT I THINK
EVERYBODY CAN SEE NOT THAT YOUNG
AND AGED OVER TIME HERE AND AT
ROCKY MOUNTAIN LABS HERE IN
HAMILTON MONTANA. I WILL TAKE
YOU THROUGH SOME DATA WE HAVE
BEEN WORKING ON AND SPECIFICALLY
I WILL TALK ABOUT CORONAVIRUSES
THAT I THINK HIGHLIGHTS WHAT MY
LAB IS INTERESTED IN. I AM ALSO
TRYING TO REALLY MAKE A POINT
THAT OBVIOUSLY I'M NOW HERE.
LET'S SAY THE PI OF THIS WORK
AND WHATEVER YOU ARE TRYING TO
HIGHLIGHT THAT THIS IS ALL OF
THE WORK OF A WHOLE SET OF VERY
DEDICATED AND VERY TALENTED POST
DOCS AND PHD STUDENTS AND
TECHNICIANS AND POST BACKS AND
TRYING TO DRIVE THAT SCIENCE
HOME NOWADAYS IS REALLY TEAM
WORK. I MIGHT BE AGING FIGURE
HAT BUT THESE PEOPLE DRIVE THE
RESEARCH IN MY LAB. I WOULD
LIKE TO POINT OUT A COUPLE
THINGS ON THIS SLIDE. THIS IS A
SLIDE THAT I START MY LONGER
PRESENTATIONS WITH. IT REALLY
HIGHLIGHTS WHAT MY LAB IS
INTERESTED IN. ON ONE HAND,
UNDERSTANDING WHERE THESE
VIRUSES COME FROM AND CIRCLE
LIKE AND WE CALL THEM NATURAL
RESERVE VOYEURS AND
UNDERSTANDING DYNAMICS IN
NATURAL RESERVE ORS AND FOCUS
AND SPILL OVER OF VIRUSES CORONA
AND NIPPO VIRUSES AND TRYING TO
LAY DOWN MORE ON THE
EXPERIMENTAL LEVEL WHICH OF
THESE FACTORS ACTUALLY
FACILITATE TRANSMISSION SO THAT
COULD BE VERY MOLECULAR. I WILL
TALK ABOUT THAT, WHICH RECEPTOR
THESE VIRUSES USE AND WHAT IS
THE DEGREE OF COMMONALITIES
BETWEEN THESE RECEPTORS FOR
INSTANCE IN THE PAT RESERVE
WOIRS AND HUMANS AND PREVALENCE
AND HOW DOES PREVALENCE IN
RESERVE OOIRS
RESERVOIRS.
AT THIS MOMENT WE ARE HAVING
REALLY BIG EMERGING INFECTIOUS
DISEASE AND WE HAVE COV2
PANDEMIC AND SPILLOVER OF H5 AND
1 PREDOMINANTLY IN POPULATIONS
IN EUROPE AND NORTHERN AMERICA
THAT IS A BIG PROBLEM AND
OBVIOUSLY NOW QUITE RECENTLY
EMERGENCE OF EXTENSIVE MONKEY
POX CIRCULATION AND FISH
TRANSMISSION AND LAYING IT OUT
IT IS NOT JUST SARSCOV2 WE HAVE
TO BE VIJ LENTD FOR A NUMBER OF
THESE EMERGING INFECTIOUS
DISEASES AND I CAME TO THE
CORONAVIRUS GAME AFTER SARZ COV
AND AT THAT TIME I WAS DOING P.
HD IN THE NETHERLANDS ON
INFLUENZA AND SARSCOV EMERGED IN
2022 AND BACK AND WE KNOW THERE
ARE SARSCOV CIRCULATING IN
VIRUSES AND BATS PARTICULARLY IN
SOUTHEAST ASIA AND THINK THE
VIRUSES SPILLED OVER FROM HORSE
SHOE BAT IN WILDLIFE MARKETS AND
RACCOON DOCS AND FROM THAT WE
SAW A COUPLE SPILLOVER EVENTS
JUST A VERY FEW SPILLOVER EVENTS
CIRCULATING IN THE EU POPULATION
AND CIRCULATED 10% FATALITY RATE
CASES AND IN 2012 WE HAD THE
SPILLOVER EVENT WITH THIS CASE
SPILLOVER WITH CORONAVIRUS AND I
STARTED TO WORK ON CORONAVIRUS
AND JUST STARTED MY LAB AND WE
TRACED IT BACK ON THE NATURAL
RESERVE OR BEING DRAM ADAIRY
CAMELS AND AS A RESULT WE SEE
CONTINUOUS SPILLOVER IN THE
HUMAN POPULATION AND SEE MRSLIKE
VIRUSES IN BAT POPULATIONS THAT
ARE REALLY SUGGESTING THAT
ANCESTRAL SOURCE OF CORONAVIRUS
IS BATS THAT I WILL GET BACK TO
A LITTLE LATER IN MY
PRESENTATION AND LOOKING AT
COMMONALITIES WE SEE QUITE SOME
COMMONALITIES AND CASE FIDELITY
RATE IS SLIGHTLY HIGH WITH MRSCV
AND DON'T SEE THAT TRANSMISSION
UNLESS YOU GET INTO NOZIOCOMIO
SITUATIONS AND THESE VIRUSES ARE
FAVORED BY HOSPITAL HUMAN TO
HUMAN TRANSMISSION AND
COMMONALITIES WITH OTHER
EMERGING INFECTIOUS DISEASES AND
NORMAL HUMAN TO HUMAN
TRANSMISSION IN THE POPULATION
MIGHT BE RELATIVELY RARE AND
THAT TRANSMISSION REALLY
FACILITATED EXTENSIVE HUMAN
TRANSMISSIONS.
OBVIOUSLY, WE CURRENTLY HAVE
SARSCOV2 WHERE LOTS OF DATA
POINTS TO POTENTIAL EMERGENCE IN
WUHAN SEAFOOD MARKET AND DON'T
HAVE ENOUGH INFORMATION WITH
SARSCOV OR [INAUDIBLE]
CORONAVIRUS TO MAKE COHESIVE
STATEMENTS THERE AND LOOKING AT
BAT VIRUS DIVERSITY, YOU SEE
REALLY THAT A COUPLE OF THINGS
REALLY STAND OUT. ONE A MASSIVE
AMOUNT OF VIRUS DIVERSITY ARE
CORONAVIRUSES THAT ARE BASICALLY
ALL OF THE DIFFERENT VIRUSES
THAT PEOPLE HAVE DETECTED IN
BATS AND MAJORITY IS
CORONAVIRUSES.
WE ARE TALKING ABOUT ALPHA AND
BETA CORONAVIRUSES AND PARAMIXER
VIER YUGSS THAT INCLUDE FOR
INSTANCE HENDRA MIX VIRUSES AND
[INAUDIBLE] THAT INCLUDES EBOLA
AND [INAUDIBLE] VIRUSES AND
RABIUS AND SHOWING THAT USED
DIVERSITY OF CORONAVIRUSES WERE
ALREADY DETECTED IN DIFFERENT
BATS ACROSS THE WORLD AND
LOOKING A LITTLE MORE CLOSER
THERE IS A PHYLOGENETIC MAP AND
TREE ON THIS END AND ALPHA
CORONAVIRUS AND BETA CORONAVIRUS
AND SEE A NUMBER OF DIFFERENT
BAT SPECIES AND BAT FAMILIES ARE
BEING THE HOST OF THE BATS YOU
CAN ALSO SEE SOME VIRUSES FOR
INSTANCE SARBACO VIRUS INCLUDES
SARS AND SARS COV2 AND IN BATS
AND PANGALINS AND THAT DETECTION
IN HOST IS SUGGESTIVE OF BROAD
HOST POTENTIAL OF THESE VIRUSES
SARBACO VIRUSES GRABBED
ATTENTION EXTENSIVELY WITH
EMERGENCE OF ORIGINAL SARS AND
SARS2 AND GOING TO TOP DOWN,
THIS PLACE, BAT SPECIES
DIVERSITY ACROSS THE WORLD AND
MORE BAT SPECIES IN A SPECIFIC
AREA, MORE YELLOW IT IS HIGHER
BAT SPECIES DIVERSITY WE SEE
HERE IN SOUTH AMERICA AND
TYPICALLY IN SUBIS A HAIRANT
AFRICA FROM THE BASIN AND IN
SOUTHEAST ASIA AND ROUGHLY 1400
DIFFERENT SPECIES OF BATS ACROSS
THE WORLD THAT DISTRIBUTED ALL
OVER THE WORLD IN EACH COUNTRY
AND CONTINENT EXCEPT ANTARC KA
AND OVERLAYING THAT WHERE THESE
ANIMALS GET SAMPLED, WE SEE
AGAIN A HIGH DEGREE OF ANIMALS
BEING SAMPLED WHERE WE SEE
HIGHEST BAT DIVERSITY AND WE
PREVIOUSLY HAVE OUTBREAKS IN
BOTH ORIGINAL SARS AROUND
OUTBREAKS IN SOUTHEAST ASIA AND
SPARK TREMENDOUS SAMPLING OF
THESE BAT SPECIES AND GOING
WHERE WE DETECT THESE
CORONAVIRUSES AND WHERE ARE IN
ALL THESE DIFFERENT BAT SPECIES
AND IN SAMPLES WHERE WE SEE
HIGHEST DEGREE OF CORONAVIRUS
HOST WE SEE THEM IN SOUTHEAST
ASIA THAT ARE REALLY SUGGESTING
THAT LOTS OF CORONAVIRUSES
CIRCULATED IN BAT SPECIES IN
SOUTHEAST ASIA AND AS I SAID MY
WORK ON CORONAVIRUS STARTED WITH
MIDDLE EAST CORONAVIRUS THAT WAS
FIRST DESCRIBED IN 2012 BY GROUP
OF RON FUGAY AT A MEDICAL CENTER
AND CLUSTERS WITH BETA
CORONAVIRUSES REMINISCIENT OF
SARS AND PEOPLE WERE ON LOOKOUT
FOR THESE VIRUSS WHAT WOULD
HAPPEN AND WE KNOW THEY HAVE
POTENTIAL AND [INAUDIBLE]
DISEASE IN HUMANS.
SO, FROM OUR END WHAT WE STARTED
WITH IS TRYING TO FULFILL
[INAUDIBLE] AND TYPICALLY WHAT
WE DO IS USE PRIVATE MODEL FOR
THIS AND WE INOCULATED THIS
MIDDLE EAST CENTERED KOR ONA
VIRUS FROM MEDICAL SCHOOL AND
THAT WAS FROM INITIAL INDEX CASE
AND CULTIVATED VIRUS AND DID
COMBINED INOCULATION IN THE
ANIMALS AND TYPICALLY DO ORAL
AND INTRANASAL AND INTRAKINNEAL
AND WE SEE OVER TIME BRONXIAL
PNEUMONIA DEVELOPING ON X-RAYS
IN ANIMALS AND IF WE THEN LOOK
ON CELLULAR LEVEL, WE SEE
REPLICATION IN TYPE 1 AND TYPE 2
SITES.
WHY IS THIS IMPORTANT? I HAVE A
NICE LAYOUT OF LOWER TRACK WHERE
WE SEE TRACEA AND BRONCHIO LI
AND LUNGS AND ALVEOLI AND THIS
IS MADE UP OF TYPE 1 AND TYPE 2
PNEUMOCITES TAKING PLACE IN TYPE
1 PNEUMOCITES AND MACROPHAGES
AND WE HAVE OBVIOUSLY VIRUS
REPLICATING HERE AND THIS IS
QUITE EXTENSIVE AND CAN HAVE
POTENTIAL TO CAUSE QUITE
EXTENSIVE DAMAGE AND IS ONE
REASON WHY WE ARE INTERESTED IN
THAT AND ON A DISEASE
PERSPECTIVE, WE WERE VERY
INTERESTED AND WE HAVE
NOZEOKOMIO OUTBREAKS IN
POPULATIONS AND SOMETHING THAT
DEFINES OF COURSE HOSPITAL
POPULATION WE HAVE A VAST DEGREE
OF DIFFERENT KIND OF IMMUNE
COMPETENT PEOPLE AND PEOPLE
HAVING A VARIETY OF BEING
IMMUNOSUPPRESSED AND DID AN
EXPERIMENT DOING RESIS MODEL AND
AGAIN WE DID INOCULATION AND WE
COMPARED THE IMMUNOSUPPRESSED
ANIMALS WITH NONIMMUNOSUPPRESSED
ANIMALS AND INTERESTINGLY ABOUT
YOU NOT UNEXPECTEDLY WE SEE HIGH
REPLICATION AND MORE SHEDDING
FROM IMMUNOSUPPRESSED ANIMALS
AND SEE HIGHER VIRAL LOADS IN
LOWER TRACT AND SUGGESTING WE
SEE EXTENSIVE REPLICATION IN
IMMUNOSUPPRESSED ANIMALS AND
OBSERVED WE SEE WAY LESS OF THEM
AND LOGICAL LESIONS IN THE LUNGS
AND CONTROL ANIMALS WE SEE OVER
HERE EXTENSIVE LEGIONS CLASSIC
CORONAVIRUS LEGIONS YOU SEE
EDEMA AND INFILTRATES AND TYPE 2
HYPOMRASHIA AND SEE IN ABSENCE
OF IMMUNOSUPPRESS THE ANIMALS
AND IN HINDSIGHT IT IS
INTERESTING DECHLO METHO ZONE IS
A DRUG USE THE IN SARS COV2
PATIENT TO SUPPRESS IMMUNE
RESPONSE AND THIS IS FIRST DATA
ON CORONAVIRUS SHOWING
IMMUNOSUPPRESSANT MODEL TO HAVE
AN EFFECT ON THE DISEASE
OUTCOME.
SO, AT THAT TIME I HAD POST DOC
STARTING IN MY LAB [INAUDIBLE]
WHO IS AN ASSOCIATE SCIENTIST IN
MY LAB AND HE WENT THROUGH THE
WHOLE TRAJECTORY OF POST DOC AND
NOW A SCIENTIST AND HE WAS VERY
INTERESTED IN WELL WHERE DOES
THE VIRUS COME FROM?
THIS WAS STILL IN THE BEGINNING
OF WHEN WE JUST IDENTIFIED
MIDDLE EAST [INAUDIBLE]
CORONAVIRUS AND RECEPTIVE VIRUS
WAS IDENTIFIED VERY RAPIDLY BY
THE GROUP OF [INAUDIBLE] ALSO RA
SP US MEDICAL CENTER AND THEY
ACTUALLY PUBLISHED A NICE
CO-CRYSTALLIZATION MODEL BETWEEN
MIDDLE EAST SYNDROME SPIKE AND
RECEPTOR D BEFORE AND AT THAT
TIME WE TALKED TO JENG ZU AT
SCRIPPS AND MODEL EXCHANGED IN
SILICO IN ALL DIFFERENT SPECIES
AND CALCULATE BINDING POE
10TIALITY TO POINT US TO
POTENTIALLY THE RESERVE OR FOR
THIS VIRUS HE SAID I COULD GIVE
IT A TRY AND ON ACCESS MORE
NEGATIVE BINDING ENERGY MORE
INDICATIVE IT IS FOR EFFICIENT
BINDING WE SEE EFFICIENT BINDING
FOR MIDDLE EAST SYNDROME SPIKE
IN HUMAN RESIS BEFORE AND NOT SO
MUCH IN COMMON ANIMAL MODELS AND
VERY GOOD BINDING TO COMMON
LIVESTOCK SPECIES IN THE MIDDLE
EAST AND WE CAN ACTUALLY GO BACK
TO THE LAB AND ACTUALLY PROVE
THAT BY EXPRESSING THE RECEPTORS
AND [INAUDIBLE] RECEPTORS ON THE
CELLS WHO DON'T EXPRESS
RECEPTORS AND WE DID IT WITH
RESIS AND MOUSE AND CAMEL AND
GOAT AND SHEEP AND MIDDLE EAST
VIRUS IS EFFICIENTLY ABLE TO
UTILIZE RESISD BEFORE AND CAMEL
AND SPECIES NOT SO MUCH AND
POINTS TO WHAT IS THE ROLE OF
CAMEL IN THE CIRCULATION OF THIS
PARTICULAR VIRUS? SO, DATA CAME
OUT ACTUALLY QUITE -- WHAT I DID
SURVEY STUDIES IN DRAM ADEAR
CAMELS IN NORTH AFRICA AND SAW
VERY HIGH PREVALENCE IN
DROMADARY CAMELS THEY ARE
EXPERIENCING IN MIDDLE EAST
CORONAVIRUS AND KNOWING WHAT
VIRUS WOULD DO IN DRAM ADAIRY
CAMELS AND TENURE TRACK YOU GET
CERTAIN AMOUNT OF START-UP FUNDS
AND IT WOULD BE GOOD TO USE MY
START-UP FUNDS TO PURCHASE A
COUPLE DRAMADARY CAMELS AND HAD
TO COME IN DR. FAUCI'S OFFICE
AND EXPLAIN WHY NIH WAS ACTUALLY
PURCHASING CAMELS AND WHEN I
EXPLAINED HE WAS GOOD WITH IT
AND SET UP A COLLABORATION WITH
COLORADO STATE UNIVERSITY WITH
DOUG BOWEN AND STUDENT IN HIS
LAB AND WE DID EXPERIMENTS
INOCULATING CAMELS INTERNASALLY
AND [INAUDIBLE] AND SEEING PANEL
UP HERE WE SEE EXTENSIVE
REPLICATION IN UPPER RESPIRATORY
TRACT AND VIRUSES SHED A LOT AND
DON'T REALLY GET SICK AND THESE
ANIMALS SHOW EXTENSIVE NASAL
DISCHARGE AND DOES IT REMIND US
OF SOMETHING COMBO COMBO VIRUS
AND YOU DON'T GET THAT MUCH SICK
BUT START TO HAVE LOTS OF NASAL
DISCHARGE AND LOOKING AT VIRUS
REPLICATION THROUGHOUT THE
TISSUES WE SEE AGAIN IT IS
REALLY FOCUSED ON UPPER
RESPIRATORY TRACT AND IN CAMELS
WE SEE EFFICIENT RESPIRATORY
REPLICATION SUGGESTING AT THIS
TIME IS VERY GOOD EVIDENCE THAT
THEY MIGHT INDEED PLAY A BIG
ROLE IN THE CIRCULATION AND
SPILLOVER OF MIDDLE EAST
RESPIRATORY CORONAVIRUS AND TOOK
THAT A STEP FURTHER AND IT IS
NICE IF YOU CAN SHOW THAT
ANIMALS GET INFECTED BUT DO THEY
ACTUALLY TRANSMIT IT VERY
EFFICIENTLY AND A- SETTING UP
SECOND EXPERIMENT DEMOS
INOCULATED WITH SYNDROME AND
CORONAVIRUS AND HAVE [INAUDIBLE]
ANIMALS AND PUT A ONE-ON-ONE
NAÏVE CAMEL WITH PREVIOUSLY
INFECTED CAMEL AND LOOK WHAT
WOULD HAPPEN. RED CAMELS ARE
ONES THAT WE INOCULATED AND,
AGAIN, VERY ROBUST INFECTION IN
UPPER RESPIRATORY TRACT AND DAY
2, WE HAD TWO GROUPS PUTTING
NAÏVE CAMEL WITH IT SEEING IN
BLUE NAÏVE CAMELS GOT INFECTED
WITH IT AFTER TWO DAYS AND WERE
ABLE TO EFFICIENTLY REPLICATE
AND SHED VIRUS AS ORIGINALLY
INFECTED VIRUS REALLY DRIVING
HOME THAT POINT THAT DR
DR. DRAMADARY CAMELS MIGHT PLAY
A BIG ROLE IN CIRCULATION AND
MIDDLE EAST CORONAVIRUS AND WHAT
ABOUT OTHER CAMELETS AGAIN? I
GOT QUITE KNOWLEDGEABLE IN
CAMELETS AND THEY ORIGINATE FROM
THE AMERICAS AND DRAM EDARY
CAMELS ANCESTRAL MOVE OVER THE
BARING STRAIGHT OVER HERE AND
ENDED UP OVER HERE AND ONE
IMPORTANT THING TO KNOW ALL DRAM
ADAIRY CAMELS ARE DOMESTICATED
AND THERE IS A SMALL POPULATION
OF WILD [INAUDIBLE] CAMELS IN
MONGOLIA AND CHINA OVER HERE AND
IMPORTANTLY YOU CAN SEE
DISTRIBUTION OF THE DRAM EDARY
CAMELS AND [INAUDIBLE] CAMELS
OVERLAP AND WE WERE ACTUALLY
INTERESTED TO SEE WHERE THESE
CAMELS SUSCEPTIBLE OR NOT AND
REPEATED EXPERIMENT WE DID FOR
DRAM EDARY CAMELS AND SHOW
SUFFICIENT SHEDDING SUGGESTING
THAT THESE ARE ALSO VERY
SUSCEPTIBLE THAT WOULD POINT TO
A WAY GREATER RISK FOR ZOONOTIC
SPILLOVER OF ANIMALS INTO HUMAN
POPULATION THAN PREVIOUSLY
RECOGNIZED AND SET IT UP WITH
COLLABORATION WITH A GROUP IN --
STARTING TO DO SURVEYS IN MON
GOALA AND REDUCING ZERO
PREVALENCE OF RESPIRATORY
SYNDROME IN CORONAVIRUS IN THIS
REGION AS WELL. OBVIOUSLY, YOU
CAN DO EVERYTHING YOU WANT IN
THE LAB BUT ONLY TAKES YOU SO
FAR. WE IMMEDIATELY WHEN THE
FIRST CASES THAT WERE IDENTIFIED
IN SAUDI AIR-ABIA THERE WAS
RESPECTIVE OUTBREAK IDENTIFIED
IN JORDAN AND SET UP FIELD WORK
OVER THERE AND STARTED TO SAMPLE
DRAM EDARY CAMELS THROUGHOUT
JORDAN AND SYRIA AND IRAQ AND
SAUDI AIR-ABIA AND ISRAEL AND
LEB AN NONE AND SAMPLING SIZE
ARE OVER HERE AND WE SAW THAT WE
SEE AN INCREASE IN POSITIVITY IN
YOUNG DRAM EDARY CAMELS AND
CORONAVIRUS BY PCR IS IN CAMELS
BETWEEN SAY 1 AND 3 YEARS OLD
AND OLDER THEY GET LESS
PREVALENCE THEY HAVE AND YOU CAN
LOOK AT ZERO PREVALENCE AND SEE
CONTINUOUS INCREASE IN ZERO
PREVALENCE THROUGHOUT THE
POPULATION AND OLDER THEY GET
HIGHER PREVALENCE AND LOOKING AT
STRENGTH OF ZOONOTIC RESPONSE
AND SEE INCREASE IN THIS
RESPONSE AND THIS IS SUGGESTIVE
THAT IT REALLY KIND OF BEHAVES
LIKE A CLASSIC KIND OF CHILDHOOD
DISEASE WITH NAÏVE YOUNG DRAM
EDARY CAMELS BECOMING INFECTED
AND HAVE AN IMMUNE RESPONSE
AFTER 2 OR 3 YEARS EXPOSURE AND
HAVE ENOUGH IMMUNE RESPONSE THAT
YOU ACTUALLY DAMPEN THE
PREVALENCE OF THE MIDDLE EAST
AND RESPIRATORY SYNDROME ACTUAL
PREVALENCE AND IN MY GROUP,
SIVER WAS INTERESTED IN WHAT
GENETIC DYNAMICS OF THIS VIRUS
FROM DRAM EDARY CAMELS FROM
JORDAN AND SHE COMPARE THE ALL
OF THE FULL GENOME SEQUENCES OF
THE CORONAVIRUS FROM HUMANS AND
DRAM EDARY CAMELS AND
[INAUDIBLE] WITH EACH OTHER AND
INTERESTINGLY COMPARING SAUDI
AIR-ABIA AND JORDAN YOU SEE
DIFFERENT EPIDEMIOLOGICAL
SIGNATURES IN GENETIC MAKEUP OF
THESE VIRUSES.
BASICALLY SUGGESTING THAT IN
JORDAN WHERE THEY HAVE ACTUALLY
RELATIVELY FEW DRAM EDARY CAMELS
AND DON'T IMPORT MANY DRAM EDARY
CAMELS WE SEE LIMITED GENETIC
DIVERSITY AND VIRUS GOES IN AND
GOES THROUGH THAT POPULATION AND
THEN ACTUALLY GETS OUT OF THE
POPULATION UNTIL IT IS SEATED
AGAIN OPPOSED TO SOMETHING LIKE
SAUDI AIR-ABA SUPPORTING DRAM
EDARY CAMELS FROM NORTH AFRICA
AND WITH IMPORT OF DRAM EDARY
CAMELS REPORT MIDDLE EAST
SYNDROME CORONAVIRUS FROM THESE
REGIONS AS WELL AND DIVERSITY IS
BIGGER IN SAUDI AIR-ABIA OPPOSED
TO JORDAN AND WE GOT BACK TO THE
RESERVIOR WE DID INOCULATION
STUDY AND IN THE REAL WORLD
FRUIT BAT AND SAW IN MIDDLE EAST
AND CORONAVIRUS REPLICATES IN
ANCESTRAL BAT RESERVIOR AND
INTERESTING WHEN WE DID THIS
EXPERIMENT WE DIDN'T REALLY KNOW
MUCH ABOUT THE DRAM EDARY CAMEL
AND HOW MUCH OF A RESERVIOR IT
WAS AT THAT TIME AND IS
INTERESTING AND TELLS ABOUT
CROSS-SPECIES POTENTIAL FOR THIS
PARTICULAR VIRUS AND YOU SEE
HERE THE STAINING IN THE LOWER
RESPIRATORY TRACT IN THE LUNGS
IS INDICATIVE OF THE VIRUS
REPLICATION AND THESE ANIMALS
DIDN'T GET SICK SHEDDING OVER
TIME ANIMALS DIDN'T GET SICK AND
WERE ABLE TO RUDIMENTARY LOOK AT
THIS DAMPENED RESPONSE
SUGGESTING THAT ANIMALS ARE ABLE
TO ACTUALLY CONTROL INFECTIONS
QUITE WELL AND ARE STILL ABLE TO
SHED AND TO REPLICATE BUT NOT
REALLY GET SICK.
SO, ANOTHER POST DOC IN MY LAB,
DR. MICHAEL LEPCO WAS INTERESTED
SO WE HAVE A NEW EMERGING
CORONAVIRUSES AND KNOW WHAT
RECEPTOR IS DPP4 AND HOW WE CAN
ACTUALLY LOOK IN ALL OF THE
DIFFERENT -- A VARIETY OF
DIFFERENT BAT SPECIES AND WHAT
DPP4 AND WHAT THE RECEPTOR LOOKS
LIKE AND WE SEE IT OVER HERE AND
HOW WELL DOES THE MIDDLE EAST
RESPIRATORY CORONAVIRUS SPIKE IS
ACTUALLY ABLE TO UTILIZE ALL OF
THE DIFFERENT SPIKES AND WE SEE
THAT HERE THE HUMAN DPP AND DPP4
HAS THE CONTROL AND WE CAN SEE A
BIG VARIATION IN HOW WELL MRS
SPIKE IS ABLE TO BIND TO DPP4
AND WE WERE OBVIOUSLY VERY
INTERESTED IN THIS PARTICULAR
DPP4 AND THIS MODUS ROTUN DOUSE
A VAM P PYRBAT AND NEWER SPECIES
AND WERE ABLE TO ACTUALLY
PINPOINT THAT TWO MUTATIONS AND
POSITION 295 AND 317 IN THE DPP4
WERE PROBABLY THE RESULT OF THIS
LESS BINDING AND ANY OF YOU
WOULD THEN REVERSE MUTATE AND DO
THE EXPERIMENT AGAIN AND SEE
THAT DPP4 WITH THESE TWO
MUTATIONS WAS ABLE AND WAS THEN
ABLE TO SUSTAIN VERY GOOD
REPLICATION.
WHY IS THIS IMPORTANT?
I THINK IT ACTUALLY SHOWS YOU
SOMETHING ABOUT THE EVOLUTIONARY
STRATEGIES AND ADAPTATION OF
VIRUSES TOWARDS RESPECTIVE BAT
HOST AND YOU HAVE TO REMIND THAT
THE CORONAVIRUS IS LARGE KP
VIRUSES WITH A PROOFREADING
MECHANISM AND PEOPLE INITIALLY
THOUGHT THAT ABILITY TO ADAPT
AND MUTATE WAS SIGNIFICANTLY
LOWER AND WE ACTUALLY SHOW HERE
THAT THIS IS A STRATEGY BUT HOW
WOULD THAT ACTUALLY PLAY OUT IF
YOU DO AN ACTUAL IN VITRO
EXPERIMENT WHERE YOU TRY TO
ADAPT MIDDLE EAST RESPIRATORY
CORONAVIRUS TO THIS MODUS
ROTUNDUS BEFORE AND WHAT MICHAEL
DID AND WE TOOK THESE CELLS
EXPRESSING THIS DPP FOUSH R 4
AND ONE THAT BINDS AND USES AND
MRS SPIKE CAN BIND TO THAT A
LITTLE BIT BUT NOT THAT
EFFICIENT AND [INAUDIBLE] OVER
TIME AND RAPIDLY WE SEE
MUTATIONS EMERGING AND MUTATIONS
THAT REALLY MADE THESE VIRUSES
CAPABLE OF VERY EFFICIENT
UTILIZING THIS ECREPTOR AND
INTERESTINGLY, THESE WERE NOT
THE SAME MUTATIONS THAT WE
ACTUALLY OBSERVED WHEN WE DID
THE COMPARISON BETWEEN THE HUMAN
AND MODUS ROTUNDUS SHOWING
DIFFERENT ADAPTATION STRATEGIES
THAT THE BATS CAN HAVE. SO, I
THINK THAT THIS IS LIKE PART OF
THE TALK WHICH GOES A LITTLE BIT
INTO TRANSMISSION.
PART OF MY THINKING HAS BEEN
KIND OF MOLDED BY INITIAL WORK
WITH STUDENTS WORKING WITH
[INAUDIBLE] AND WE WERE WORKING
ON H1 INFLUENZA AND IN
COMPARISON TO SEASONAL INFLUENZA
H32 AND GOING TO RESPIRATORY
TRACK WE SEE OVER HERE FROM
UPPER TO LOWER AND SEASONAL
INFLUENZA EFFICIENT BINDING TO
UPPER RESPIRATORY TRACT AND
LOWER RESPIRATORY TRACT AND
EFFICIENT TRANSMISSION AND WHAT
INFLUENZA VIRUS DO AND NOT SO
MUCH BINDING TO UPPER
RESPIRATORY TRACT AND EFFICIENT
BINDING TO LOWER RESPIRATORY
TRACT AND TRANSMISSION AND
EFFICIENT IN ACTUALLY CAUSING
DISEASE AND USING THAT PARADIGM
TO COMPARE INSTANCE IN THIS CASE
NOT TWO VIRUSES BUT TWO HOSTS
AND DRAM EDARY CAMELS AND
TRANSMISSION AND PROXY FOR
HUMANS NO REPLICATION
RESPIRATORY TRACT AND NOT VERY
EFFICIENT TRANSMISSION.
SO, THAT KIND OF DATA PUTS USING
TO SECOND PART OF MY TALK AND
TRYING TO SHOW WORK WE HAVE BEEN
DOING WITH NOV EL-CORONAVIRUS
EMERGING AT END OF 2019 AND WHEN
SOMETHING LIKE THAT HAPPENS YOU
ARE ACTUALLY TRYING TO PUT IT IN
PERSPECTIVE AND IN THIS CASE, WE
ARE ACTUALLY LIKE WORKING ON
COMMENTARY THAT IS NEW JOURNAL
OF MEDICINE EARLY IN THE
PANDEMIC TRYING TO POINT ON SOME
GAPS OF KNOWLEDGE AND THIS IS
EPIDEMIOLOGICAL PYRAMID THAT
SHOWS BASICALLY HOW HARD IT IS
IF YOU HAVE VIRUS MILD OR
ASYMPTOMATIC LOGICALLY TO
CONTAIN IT BASED ON SYNDROMIC
SURVEILLANCE AND SYNDROMIC
SURVEILLANCE THINK OF EBOLA
VIRUS CAUSES SEVERE DISEASE AND
ALSO STARTS TO SHED AND BE
INFECTIOUS AFTER YOU ARE ILL AND
INFLUENZA WHERE YOU ACTUALLY
START TO ALREADY SHED AND BE
INFECTIOUS BEFORE YOU BECOME
SICK AND WHAT WE HAVE SEEN WITH
SARSCOV2 WITH THE FIRST CASE
DETECTION IN THE US AND WAS
PROBABLY ALREADY EXTENSIVE
CIRCULATION BEFORE DETECTION IN
THAT INITIAL CASE AND MY GOAL
SHIFTED FROM MIDDLE EAST
SYNDROME CORONAVIRUS A YEAR
BEFORE THE PAN EMIC TO WORK ON
THE BETA CORONAVIRUS AND BETA
CORONAVIRUS USES THIS A2
RECEPTOR AND WENT TO GEN BANK
AND DID ALL-OUT SEARCH LOOKING
FOR ALL SEQUENCES OF BETA
CORONAVIRUSES AND CAME DOWN WITH
7,000 SEQUENCES AND AFTER
FILTERING CAME UP WITH 29 USABLE
SEQUENCES OF BAT CORONAVIRUS
WITH RECEPTOR BINDING SPIKE THAT
HE COULD USE IN HIS EXPERIMENTAL
SETUP.
HE DESIGNED TWO-DOOR TYPE ENTRY
SYSTEM. HE BASICALLY USED
GENERIC SPIKE WHERE HE WAS ABLE
TO SWAP OUT RBD CASSETTE BACK
AND FORWARD. HE COULD ACTUALLY
LIKE VERY RAPIDLY MAKE ALL OF
THESE DIFFERENT MUTANTS THAT
HAVE RECEPTIVE BINDING DOMAIN OF
ALL OF THE VIRUSES AND EXPLORE
WHICH RECEPTOR THEY WOULD USE
AND SEE HERE PARTICULARLY ONE
BETA CORONAVIRUS USES A2
RECEPTOR AND INTERESTING AT THAT
TIME WE KNOW SARS COV HAD QUITE
AN EXTENSIVE EPIDEMIC AND
JANUARY 11TH FULL GENOME
SEQUENCE BECAME AVAILABLE OF
SARS COV2 AND IN 11 DAYS WAS
ABLE TO SYNTHESIZE RBD AND CLONE
INTO PROTOTYPE AND WAS ABLE TO
SHOW SARS COV2 USES ACE 2 WHICH
WE HAD A GOOD SUSPICION THIS
WOULD BE A BINDER AND WE DIDN'T
HAVE FORMAL PROOF AND ON TOP OF
THAT WHAT HE ALSO SHOWED IS IF
YOU LOOK AT FILE OJ ON ANY OF
SPIKE RBD AND DIFFERENT GENE
DEPENDENT RNA POLYMERASE YOU SEE
DIFFERENT PHYLOGENY SUGGESTING
THAT BESIDES ADAPTATION OF
MUTATIONS I SHOWED IN A COUPLE
SLIDES PREVIOUSLY RECOMBINATION
AND PICKING UP WHOLE PARTS OF
RBD BETWEEN THESE DIFFERENT
RELATED BUT DIFFERENT VIRUSES IS
EVOLUTIONARY STRATEGY OF THESE
CORONAVIRUSES AND WE WERE ABLE
TO GET OUR HANDS ON THE VIRUS
REALLY QUICKLY AND THERE WAS A
COLLABORATION WITH CDC AND
NATALIE AND SUE VERBER AND THEY
WERE INTERESTED IN DOING QUITE
SOME BASIC EXPERIMENTS ON
ENVIRONMENTAL STABILITY AND HERE
WE WERE USING ORIGINAL SARS SO
2003 AND 2004 STRAIN OF SARS
COMPARING IT THAT WITH NOVEL
EMERGING VIRUS, WA1 SARS COV2
AND BASICALLY SAW VERY GOOD
STABILITY IN AEROSOLS UP TO
THREE HOURS AND RAPID REDUCTION
ON SURFACE LIKE CUPBOARD AND
STAINLESS STEEL PLASTIC AND
COULD REALLY MODEL THAT QUITE
WELL.
WE MADE A COUPLE INTERESTING
OBSERVATIONS AND PARTICULARLY
LIKE OBSERVATIONS ON
TRANSMISSION.
AEROSOL STABILITY PER-SE DOESN'T
REALLY POINT TOWARDS INCREASED
RISK OF AEROSOL TRANSMISSION;
HOWEVER, COMPARISON BETWEEN SARS
1 AND WHERE WE HAVE PRETTY GOOD
ID ABOUT EPIDEMIOLOGY OF THE
VIRUS EVOLVED AND ROUTE OF
TRANSMISSION OF THE VIRUS REALLY
SUGGESTED THAT PEOPLE SHOULD
POINT AND BE ON LOOKOUT OF
POTENTIAL AEROSOL TRANSMISSIONS.
IT WAS OBVIOUSLY NOT NECESSARILY
WHAT THE MEDIA TOOK AWAY FROM
THIS AND MEDIA ACTUALLY GOT AND
CREATED QUITE SOME MEDIA FRENZY
AND OUR LAB WAS RESPONSIBLE FOR
HANDWASHING AND SANITATION
EFFORTS BUT DON'T THINK IT IS
NECESSARILY A BAD THING.
WE HAD THE VIRUS AND WANTED TO
REALLY ESTABLISH AN ANIMAL MODEL
AT THAT TIME AND TRYING TO
UNDERSTAND ON THE ONE HAND
HEPATOGENESIS AND TEST COUNT
MEASURES AND RECENT MODEL USING
IN MIDDLE EAST SYNDROME
CORONAVIRUS AND USING SARS COV2
STRAIN ISOLATED FROM THE CASE IN
THE US AND DID A COMBINATION OF
ROUTES AND WE SEE ON THIS AFTER
INOCULATION WE SEE AN INCREASE
IN CLINICAL STORES TO MEASURE
HOW SICK THE ANIMALS ARE AND
AGAIN VERY SIMILAR TO MIDDLE
EAST RESPIRATORY CORONAVIRUS WE
SEE DEVELOPMENT OF PNEUMONIA IN
LOWER RESPIRATORY TRACT AND
INFECTION IS TRANSIENT AND MOUTH
MODEL DISEASE IN ANIMAL MODEL
AND TYPICALLY AROUND DAY 14 IT
IS RESOLVED AND SEEING GROSS
[INAUDIBLE] YOU SEE LESIONS ON
LOBES AND THIS BASICALLY AT END
OF DAY 21, MOST LESIONS ARE
RESOLVED AND HEPATOLODGE COOLLY
IT LOOKS LIKE THIS LARGE PART OF
LUNGS AFFECTED BY SARS COV2 AND
WHAT NORMAL LUNGS WILL LOOK LIKE
AND OPEN SPACES AND WHERE THEY
TAKE PLACE AND NO SWABS AND
RECTAL SWABS AGAIN POINTING
LARGELY TOWARDS UPPER
RESPIRATORY TRACT VIRUS ON
SHEDDING END AND SEE ACTION OF
VIRUS IN THE MOUTH AND WE TAKE
BRONXIAL [INAUDIBLE] TO REALLY
UNDERSTAND THE REPLICATION OF
LOWER RESPIRATORY TRACT NOT SO
MUCH IN GENITAL TRACT AND
[INAUDIBLE] WE DIDN'T DETECT ANY
VIRUS SHEDDING AND POINTING OUT
A LITTLE MORE MORPHOLOGY THESE
REALLY KIND OF CLASSIC LESIONS
IN CORONAVIRUS LESIONS INCLUDING
EDEMA AND FIBER DEPOSITS TYPE 2
HYPERMRASHIA AND MEMBRANES AND
SIMILAR TO MIDDLE EAST
RESPIRATORY SYNDROME CORONAVIRUS
AND RED BLOOD STAINING IS
AGAINST REPLICATING SARS COV2
AND PNEUMOSITES AND ALVEOLI
MACROPHAGE WE HAVE RAPIDLY
GOTTEN DAY AH AND WE KNOW HOW IT
INFECTS AND KNOW AEROSOL
STABILITY QUITE WELL AND CAN
MAKE ANALOGY WE FIRST DID
INFLUENCE SATURDAY AND MIDDLE
EAST RESPIRATORY SYNDROME
CORONAVIRUS AND WITH SARS COV2
WE SEE RESIDENT P OPERATION AND
UPPER RESPIRATORY TRACT AND
LOWER RESPIRATORY TRACT AND
COMPILING IT TO TRANSMISSION
RISK AND THIS SLIDE IS FROM
ACTUALLY SOME OF THE WORK WE
HAVE BEEN DOING WITH EBOLA VIRUS
WHERE MAJOR TRANSMISSION IS
REALLY DIRECT CONTACT AND BODILY
FLUID AND NOW WITH SARS COV2 WE
SEE ACTUALLY A HIGH RISK IN
DIRECT CONTACT AND HIGH RISK FOR
DROP IN AEROSOL TRANSMISSION AND
FORMAL TRANSMISSION WE THINK
TAKES PLACE AND IT IS ACTUALLY
QUITE MARGINAL OPPOSED TO DIRECT
CONTACT AND AIRBORNE
TRANSMISSION.
SO, THERE IS STILL NO LIKE
FORMAL PROOF OF THE AEROSOL
TRANSMISSION AT THAT POINT.
AND THEN DR. [INAUDIBLE] WERE
REALLY TRYING TO SET OUT HOW WE
CAN EXPERIMENTALLY PROVE THIS IS
REALLY AN AEROSOL TRANCE
MISSABLE VIRUS AND USE THE ONE
OF OUR FAVORITE ANIMAL MODELS
ENHANCER FOR THIS AND FIRST
THING THEY ACTUALLY DID IS
DEVELOP GAUGING SYSTEMS WITH DR.
BOB FISHER AND REALLY LOOKED
ADIFFERENT DISTANCES BETWEEN
CAGES AND THESE ARE INFECTED AND
THESE ARE UNINFECTED ANIMALS AND
FIRST THING THEY DID IS GENERATE
A VARIETY OF DIFFERENT PARTICLE
SIZE ON THIS END OF THE GATE AND
LIEU WHICH KIND OF PARTICLES
ACTUALLY MADE IT TO THIS END OF
THE CASE AND USED AERODYNAMIC
PARTICLE SIZER FOR THIS AND THEY
WERE ACTUALLY ABLE TO SHOW IN
THIS CAGING SETUP, THE 6 FEET,
ONLY TRUE AEROSOLS IF YOU CAN
FIND THEM THESE ARE AEROSOLS
SMALLER THAN 5 MICROMETER MAKE
IT FROM LEFT TO RIGHT AND WHAT
TRUE SETUP LOOKS LIKE IN OUR
FACILITY AND THEY WERE ACTUALLY
ABLE TO SHOW THAT USING THIS
SETUP VERY EFFICIENT
TRANSMISSION, BOTH FOUR HOURS
AFTER PLACING INOCULATED DONOR
ANIMALS WITH THE PLACENTAL
ANIMALS AND COULD GO DOWN TO 1
HOUR AND TIGHT TRAIT DOWN FOR 15
MINUTES VERY EFFICIENT AEROSOLS
PLUS AIRBORNE TRANSMISSION IN
THIS ANIMAL MODEL.
AGAIN, FOCUSING ON TRANSMISSION,
SO WE PUBLISHED THAT DATA ON
AIRBORNE STABILITY AND GOT
CONTACTED BY A DOCTOR FROM THE
EVERGREEN MEDICAL CENTER AND HE
SAID I HAVE A PROBLEM HERE. I
HAVE A PATIENT WHO IS SEVERELY
IMMUNOCOMPROMISED, ASYMPTOMATIC,
TESTED POSITIVE AND KEEPS
TESTING POSITIVE AND WHAT DO I
DO WITH IT FROM A HOSPITAL
HYGIENE POINT OF VIEW, IT WILL
BE A PROBLEM. I SAID, SEND HER
SAMPLES TO OUR LAB AND WE WILL
TEST THESE VIRUS AND WHETHER THE
SAMPLES ARE STILL INFECTIOUSES
AND HAD 2PHD STUDENTS AT THAT
TIME VICKY AND JEREMIAH WORKING
ON IT AND THEY WERE BASICALLY
ABLE TO SHOW THIS ASYMPTOMATIC
PATIENT WAS SHEDDING THE VIRUS
FOR 105 DAYS TREATED WITH PLASMA
TWICE AND UP TO DAY 77, WE WERE
ABLE TO IDENTIFY INFECTIOUS
VIRUS FROM THIS PATIENT AND WE
SEE THE CT VALUE OF THE GENOMIC
AND SUBGENOMIC AND REALLY
EXTENSIVE LONG-TERM SHEDDING
THAT AT THAT TIME WASN'T
REPORTED YET IN LITERATURE AND
DEEP SEQUENCED THE SAMPLES AND
VERY INTERESTINGLY WHEN WE TOOK
AND WHEN WE RECEIVED AND THEY
TOOK A SAMPLE FROM THIS PATIENT
AND DEEP SEQUENCE IT WE SAW A
COMPLETELY DIFFERENT VIRUS
POPULATION EVERY TIME WE
SEQUENCE THAT VIRUS AND SEE VERY
EXTENSIVE AND YOU SEE ALIGNED
EXTENSIVE DELETIONS AND
MUTATIONS AND REALLY SUGGESTING
THAT WITHIN THIS LIKE VERY
PARTICULAR IMMUNOCOMPROMISED
POPULATIONS, WE SEE EXTENSIVE --
POTENTIAL FOR EXTENSIVE
EVOLUTION THAT HAS NOW BEEN
REPORTED ON SEVERAL OCCASIONS.
SO, HOW DO YOU THEN GO ON TO
POTENTIALLY BLOCK TRANSMISSION
OF RESPIRATORY VIRUS AND
DIFFERENT LAYERS BETWEEN AND
WITHIN HOSTS AND SHEDDING AND
ENVIRONMENTAL PERSISTENT
INFECTION AND PPE AND
VENTILATION AND INCOMBINANT
CONTROL AND ACTIVE
COUNTERMEASURES LIKE VACCINATION
WORKING ON SHEDDING AND SUS
SEPTEMBER IBLT END AND ACTIVE
RECOMBINATION USING UVC AND BOB
FISHER IN MY LAB TRYING TO
ADDRESS QUESTIONS FROM PUBLIC
HEALTH FIELD WOULD SAY WE ARE
RUNNING OUT OF P. PE BASED ON
YOUR ENVIRONMENTAL STABILI
DATA COULD WE THROW MASKS FOR A
COUPLE DAYS IN LET'S SAY A SHED
AND THEY WILL BE INACTIVATED.
WE THOUGHT WE SHOULD MAYBE TEST
THAT AND USED A WHOLE VARIETY OF
INACTIVATION METHODS DRY HEAT
AND UVC AND HIDE ROTH ENPEROXIDE
THAT WERE KNOWN IN LITERATURE TO
WORK AND WE ALSO TESTED AND DID
A RESPIRATOR FIT TEST AND WE
WERE ACTUALLY ABLE TO HAVE
PEOPLE WEAR THESE MASKS AND GO
THROUGH A ROUND OF INACTIVATION
THROUGH ALL THESE METHODS AND
WERE ABLE TO MEASURE HOW WELL
THAT MASK ACTUALLY STILL
FUNCTIONED AND WHY IS IT
IMPORTANT? THEY ARE SINGLE-USE
MASKS DESIGNED TO USE ON ONE
OCCASION AND THEN THROWN AWAY
AND WE WERE ABLE TO SHOW IN
PARTICULARLY WITH VAPE ROUS
HYDROGEN PER OXIDE AND UV THAT
AFTER THREE TIMES OF USES, YOU
CAN SEE THAT MASK EFFICIENCY
ACTUALLY GOES DOWN AND STILL
WOULD WORK FOR A VAPORIZED
HYDROGEN PER OXIDE AND UV AND
YOU CAN DECONTAMINATE THAT MASK
AND HAVE TO LOOK AT EFFICIENCIES
AND IF YOUR MASK DOESN'T
FUNCTION PROPERLY ANYMORE, IT IS
NOT MUCH USE FOR PPE.
SO, WE ALSO BASED ON OUR MRS
WORK HAD A LONG-STANDING
COLLABORATION WITH THE INSTITUTE
WITH SARA GILBERT AND OXFORD
WORKING ON VIER YUGS PLATFORM
FOR VARIETY OF EMERGING VACCINE
VIRUSES SYNDROME CORONAVIRUS AND
LASAR VIRUS AND SEQUENCE FROM
SARS COV2 CAME ONLINE THEY
IMMEDIATELY STARTED TO GENERATE
AND CLONE SARS COV2 SPIKE IN THE
CONTEXT OF THIS REPRO INDICATION
DEFECTIVE ADDINO VIRUS AND ONCE
THEY GENERATED THAT LOOKED AT
IMMORAL RESPONSE AND IMMUNISTY
IN THE MODEL AND SENT TO US TO
TEST IN NONPRIMATE MODEL AND IN
THIS STUDY THAT IS NICE WHERE WE
HAVE CHIMP ADENO VIRUS VACCINE
AGAINST REPLICATION EFFECTIVE
CHIM ADENOVIRUS EXPRESSING SPIKE
IN 1 VACCINATION VERSUS 2
VACCINATIONS VERSUS CONTROLLED
VACCINATED ANIMALS VACCINE
EXPRESSIVE GFP AND VACCINE
ADMINISTRATIVE 2.5 PARTICLES TO
ANIMALS CHIMP ADENOVIRUS VACCINE
AND SAME CHALLENGE I DESCRIBED
PREVIOUSLY AND WE SEE IN THE
PANELS THAT AFTER VACCINATION WE
SAW GOOD INDUCTION OF
IMMUNORESPONSE AND ELIZA PRIME
VERSUS PRIME BOOST AND A VERY
GOOD NEUTRALIZING RESPONSE AS
WELL AND AFTER THE CHALLENGE WE
SEE A VERY GOOD PROTECTION OF
LOWER RESPIRATORY TRACT HERE AND
FLUIDS AND LOOK AT VIRUS
REPLICATION AND DETECTION IN THE
BELL FROM THE LOWER RESPIRATORY
TRACK AND TISSUE FROM NECROPSY
AND DIDN'T SEE REDUCTION IN
UPPER RESPIRATORY TRACT AND WERE
ABLE TO PROTECT ANIMALS AGAINST
DISEASE BUT NOT FROM INSPECTION
IN UPPER RESPIRATORY TRACT AND
IF YOU LOOK AT IT A LITTLE MORE
CAREFULLY IN LOWER RESPIRATORY
TRACT AND WE SEE CONTROL ANIMALS
SHOWING REALLY THAT CLASSIC
CORONAVIRUS AND NUCLEATED CELLS
EDEMA AND [INAUDIBLE]
REPLICATION HERE AND SEE ABSENCE
OF PATHOLOGICAL MARKERS IN PRIME
OR SINGLE VACCINATED ANIMALS
VERSUS PRIME BOOST VACCINATED
ANIMALS AND THIS WAS DATA THAT
UK REGULATORY AUTHORITIES NEEDED
TO START THEIR CLINICAL TRIAL
WITH THIS VACCINE.
SO, THIS WAS A TIMELINE FROM THE
DESIGN OF THE VACCINE UNTIL
OXFORD STARTED THE CLINICAL
TRIAL AND TYPICALLY PRETTY MUCH
AROUND 3 MONTHS.
THIS IS WHEN WE HAD FIRST DATA
ON RESUS MODEL THAT I PRESENTED
AND WHEN WE STARTED TO VACCINATE
THE ANIMALS AND THIS IS WHERE WE
HAD A CHALLENGE. YOU SEE IT IS
A REALLY COMPRESSED TIMELINE AND
THIS PICTURE WAS TAKEN FROM A
NEWS ARTICLE IN NATURE AND SHOWS
AMOUNT OF VACCINES BEING
DISTRIBUTED ACROSS THE WORLD OF
ALL THESE DIFFERENT VACCINES
INCLUDING CORONA PFIZER VACCINE
AND MODERNA VACCINE AND THIS IS
A PAPER THAT CAME OUT THAT IS
REALLY SUGGESTING THAT MAJORITY
OF SUPPORTED BY VACCINATION WERE
DONE WITH ASTRA ZENNICA VACCINE
OR PFIZER VACCINE AND BROAD
DISTRIBUTIONS OF ASTTRA ZENNIC
AH VACCINE AND IN COUNTRIES AND
MRNA VACCINES LIKE MODERNA AND
WE HAVE SHOWN GOOD PROTECTION OF
LOWER RESPIRATORY TRACT WE WERE
STILL LIKE WHAT IS GOING ON WITH
UPPER RESPIRATORY TRACT AND CAN
WE DESIGN BETTER VACCINES AND
POTENTIALLY TRY TO REDUCE
SHEDDING AND REPLICATION IN
UPPER RESPIRATORY TRACT AND
[INAUDIBLE] AND JODY A PHD
STUDENT IN MY LAB WERE
INTERESTED IN POTENTIAL MUCOSAL
VACCINE IN IMMUNE SYSTEM AND
THIS IS A SLIDE FROM FLORRI
ANAGRAM AR SHOWING IF YOU HAVE
NATURAL INFECTION YOU INDUCE
MUCOSAL [INAUDIBLE] VERSUS
SYSTEMIC ONE AND -- YOU ARE
LIKELY INDUCED SYSTEMIC RESPONSE
THAT MIGHT PROTECT AGAINST THE
DISEASE BUT NOT NECESSARILY
REPLICATION IN THE UPPER
RESPIRATORY TRACT.
SO, THEY DESIGNED A VACCINE
WHERE WE ADMINISTRATED ASTTRA
ZENNICA VACCINE INTRANASALLY
USING SPRAY DEVICE AND
[INAUDIBLE] IS A COLD VIEFRUS
AND THOUGHT IT WOULD BE A NIGHT
PLATFORM TO MOVE INTO MUCOSAL
VACCINATION CHALLENGE AND
LOOKING AT SHEDDING IN UPPER
RESPIRATORY TRACT WE SEE A QUITE
MARKED REDUCED NOT [INAUDIBLE]
REDUCTION BUT REDUCTION SHEDDING
UPPER RESPIRATORY TRACT
MAINTAINING REDUCTION IN
REPLICATION IN LOWER RESPIRATORY
TRACT AND IN ONE END INDUCING
BETTER PROTECTIVE RESPONSE IN
UPPER RESPIRATORY TRACT
MAINTAINING RESPONSE IN LOWER
RESPIRATORY TRACT SHOWING
MORPHOLOGY AND CONTROLLING
ANIMALS WITH LESIONS AND VIRUS
REPLICATION WITH CHEMISTRY AND
ABSENCE OF THAT IN INTRANASAL
INOCULATED ANIMALS.
AND SO THERE WAS ALREADY QUITE
SOME DATA ON AVAILABILITY OF
VACCINES TO BLOCK TRANSMISSION
IN HOUSEHOLD SETTINGS THAT
OBVIOUSLY PUSHED A LITTLE ON
SIDELINES BY EMERGENCE OF
VARIANCE OF CONCERN AND WE WERE
VERY INTERESTED IN THAT AND WHAT
ARE EVOLUTIONARY BENEFITS OF THE
NEW VARIANTS AND THIS, AGAIN, IS
A STUDY DONE BY JUDY AND QUAY
WHO DESIGNED TRANSMISSION MODEL
I TALK ABOUT NOW PREVIOUSLY BUT
NOW ONLY DO A SINGLE INFECTED TO
SENTIN OL BUT MODEL A
TRANSMISSION CHAIN AND EXPOSE
SECOND SEINE CONTINUE OL TO
THESE ANIMALS AND OVER NOT JUST
USING ONE VIRUS BUT MIXTURE IN
THIS CASE WA1 ANCESTRAL VIRUS
WITH FIRST VAR YEN SHAL CONCERN
ALPHA AND DEEP SEQUENCE VIER
YUGS COMING OUT MOVING TO
TRANSMISSION CHAIN AND ORIGINAL
ANCESTRAL VIRUS IS BLUE AND
ALPHA VARRANT IS IN RED AND SEE
AFTER TRANSMISSION THERE IS
ALMOST VERY RAPIDLY COMPLETELY
TAKING OVER BY THE A--LE FA
VARIANT OVER THE ORIGINAL I WILL
SAY REALLY SUGGESTING THAT THE
EVOLUTIONARY PRESSURE IS REALLY
IN INITIAL VARIANTS OF CONCERN
ON TRANSMISSION. SO, HOW IS
THAT FOR OMICRON?
OMICRON IS OBVIOUSLY EXTENSIVELY
DIFFERENT. IT THIS IS A REALLY
NICE WAY OF SHOWING WHERE WE USE
VIRUS DATA OF HAMSTERS WITH --
WE HAVE BEEN INFECTED WITH
VARIANTS OF CONCERN AND IF WE
LOOK AT AVAILABILITY OF THESE
AGAINST GENERATED AGAINST FOR
INSTANCE DELTA TO NEUTRALIZE
OMICRON AND VICE VERSA AND USING
TECHNOLOGY CALLED ANTHROGENIC
CARTOGRAPHY BY RUSSELL
UNIVERSITY IN AMSTERDAM HE COULD
ACTUALLY DISPLAY THAT NICE THAT
THIS IS ANTIGENIC DISTANCE
BETWEEN ALL PREVIOUS VIRUS AND
VARIANTS OF CONCERN AND OMICRON
REALLY SUGGESTING THAT OMICRON
CHANGED THE KIND OF LANDSCAPE
LITERALLY.
SO, CAN WE MODEL THAT AS WELL?
AGAIN, THIS IS A STUDY BY YULIA.
WELL, IF OMICRON IS ANTIGENIC
AND THIS EMERGED IN CONTEXT OF
PREEXIST IMMUNITY AND SHE WAS
TRYING TO DO INFECTION
EXPERIMENT IN TRANSMISSION MODEL
WHERE ON ONE HAND WE HAVE
INTERMUSSICALLY VACCINATED
MODELS WITH ASTTRA ZENNICA
VACCINE AND INTRANASALLY VACCINE
IN HAMSTERS AND PREVIOUSLY
EXPOSED MAMMALS AND DELTA AND
EXPOSED THEM AND MOVED THEM
THROUGH TRANSMISSION CHAIN THEY
WILL BE EXPOSED TO COMBINATION
OF ONE-ON-ONE AGAIN WITH DELTA
AND OMICRON AND FIRST THING WE
CAN SHOW HERE IS REALLY THAT
THERE IS A LETTERIZED DEGREE OF
IMMUNORESPONSE -- AND PREVIOUSLY
INFECTED AND PREVIOUSLY INFECT
INDUCES STRONGEST
IMMUNORESPONSE.
SO, IF WE THEN TAKE THIS
ONE-ON-ONE MIXTURE IN ANIMALS
THROUGHOUT TRANSMISSION CHAIN,
INTERESTING PART IS OMICRON
REALLY DOESN'T LIKE TO TRANSMIT
IN HAMSTERS.
HOWEVER, WE WERE ABLE TO TEASE
OUT SOME [INAUDIBLE] THAT
STRONGER IMMUNORESPONSE THAT I
SHOWED OVER HERE MORE RELATIVE
OMICRON YOU GET SUGGESTING THAT
OMICRON REALLY FAVORS LIKE AN
ENVIRONMENT OF ANTIBODIES TO BE
ABLE TO COMPETE WITH ALL
PREVIOUS VARIANTS.
AND THEN YOU CAN ACTUALLY LOOK
IF YOU MOVE IT THROUGH THE CHAIN
AND HOW WELL THESE DIFFERENT
VACCINATION STRATEGIES AND
PREVIOUS EXPOSURE STRATEGIES
COULD BLOCK VACCINATION AND YOU
SEE THAT IT IS ACTUALLY EASIER
TO BLOCK AIRBORNE TRANSMISSION
THAN DIRECT CONTACT TRANSMISSION
AND, AGAIN, INTRANASAL
VACCINATION AND PREVIOUSLY
EXPOSED WORKING EQUALLY AS WELL
BEING ABLE TO REDUCE
TRANSMISSION AND THERE IS
REDUCTION OF TRANSMISSION THAT
DOESN'T CHAIN AND TAKE PLACE OF
ONE CHAIN AND YOU HAVE TO
ACTUALLY MEASURE IT OVER A
COUPLE ROUNDS OF TRANSMISSION.
SO, WHERE WILL WE GO IN MY LAB?
ONE EXCITING POINT WE ARE
WORKING ON IS COUNTER MEASURES
VERSUS FUTURE EMERGING VIRUSES
AND BOB IS WORKING ON USING
INITIAL MODEL OF TRANSMISSION
AIRBORNE MODEL AND USING
PREEMPTIVE MODELS TO BLOCK
TRANSMISSION WHERE HE WAS ABLE
TO SHOW THAT IF YOU USE UBC, YOU
CAN COMPLETELY BLOCK
TRANSMISSION AND REALLY LIKE A
PREEMPTIVE MEASURE AND WORKING
WITH PAMELA'S LAB ON MOSAIC
VACCINES THAT ARE NANOPARTICLES
EXPRESSING DIFFERENT RBDS FROM A
WHOLE VARIETY OF DIFFERENT
CORONAVIRUSES SHOWING PROTECTION
NOT ONLY AGAINST SARS COV2 BUT
SARS COV1 AND WHERE WE ARE GOING
ON WITH THE LAB AND NOT TALKING
TOO MUCH ABOUT THAT AND DR.
HOLLAND POINTED IT OUT BUT PART
OF MY WORK IS IN SUBIS A HAIRANT
AFRICA AND FOCUSED ON EMERGING
INFECTIOUS DISEASES INCLUDING
IMMUNOVIRUSES POINTING OUT WE
SEE DRAMATIC CHANGES NOT OWE
NENL AFRICA THAT IS OBVIOUSLY
TAKEN WORLDWIDE BUT SEE
URBANIZATION AND DEFORESTATION
AND GREATER POPULATION THAT THEY
COULD ALL HAVE AN INFLUENCE ON
ABILITY TO INCREASE ZOONOTIC
SPILLOVER AND WE HAVE LOOIM
LIGHT THAT IS A LITTLE BIT IN
RECENT COUPLE OF WEEKS THAT IS
MONKEY POX AND HAVE WORKED ON
MONKEY POX SPILLOVER IN THIS
PART OF THE REPUBLIC OF CONGO
BASIN THAT IS DISTINCT FROM ONE
CAUSING OUTBREAK 10% AND STARTS
INITIALLY WITH YOUNGER CHILDREN
AND WHY IS THAT IMPORTANT?
I THINK THE RE CECENT DEVELOPME
WITH MONKEY POX THAT IS A NICE
COMPILATION OF DATA BROUGHT
TOGETHER BY JAY POST DOC IN MY
LAB THAT IS CLASSIC CIRCULATION
OF MONKEY POX ENDEMIC AREA THAT
WE SEE SPILLOVER INTO THE HUMAN
POPULATION AND THIS IS THE
CURRENT CIRCULATION OF THIS WEST
AFRICAN VARIANT OF MONKEY POX
THAT IS SPREADING THROUGHOUT
WORLD INITIALLY REALLY TARGETING
THE MSN POPULATION AND REALLY
POINTS OUT THAT, AGAIN, NOW WE
HAVE ALL THIS DETECTION OVER
HERE AND DIAGNOSTICS AND WHILE
WE ARE STILL ABLE TO FAIL SET UP
SIGNIFICANT SURVEILLANCE AND
DIAGNOSTICS THAT IS LIKE A
CLASSIC NEGLECTED TROPICAL
DISEASE ON THIS END AND WE WANT
TO PUSH FOR NOT ONLY DEVELOPMENT
OF DIAGNOSTICS BUT BRINGING THEM
WHERE WE EXPECT OUTBREAKS
BRINGING THEM IN CLINICAL TRIALS
IN COUNTRIES FOCUSING ON VACCINE
CLINICAL TRIALS AND INTERPRETIVE
CLINICAL TRIALS IN THESE AREAS
AND LASTLY THAT OF COURSE GOES
HAND IN HAND WITH CAPACITY
BUILDING. MY LAB HAS BEEN QUITE
ACTIVE IN THAT FROM THE WEST
AFRICAN EBOLA OUTBRAEM OF 2013
AND 2014 AND DR. BOB FISHER
WORKING IN REPUBLIC OF CONGO
TRAINING PEOPLE IN THE CLASS AND
TRAINING ISOLATED AND WE SEE
THEM REALLY TRYING TO WORK ON
TRAINING OF PEOPLE IN JORDAN TO
DO MIDDLE EAST RESPIRATORY
SYNDROME CORONAVIRUS
SURVEILLANCE AND ACTIVE FELLOW
DR. OOIR EVEN WUSHU BACK INGANA
AND SPEAR HEADING -- AND THEY
HAVE MONKEY POX OUTBREAK INGANA
AS WELL AND DRIVING HOME WE NEED
TO INVEST IN COUNTRIES THAT
NEEDS TO BE SUSTAINABLE AND WE
NEED TO TRAIN THESE PEOPLE MORE
AND BETTER.
OBVIOUSLY, AS I SAID ALREADY,
THIS IS A HUGE AMOUNT OF WORK
THAT HAS LOTS OF DIFFERENT
COLLABORATORS POINTING OUT IN MY
LAB HERE IN THE MOMENT A LOT OF
WORK IS DONE BY ALL OF THEM AND
FORMER LAB MEMBERS FROM 2020 TO
2022 AND ALL PEOPLE IN
LABORATORY OF VIROLOGY AND TEAM
WORK DOESN'T JUST INCLUDE
RESEARCH BUT LARGE SUPPORT STACK
AT ROCKY MOUNTAIN LABORATORIES
FROM VEGETARIAN AND RECENT
BRANDS AND SUPPORT STAFF THAT
INCLUDING LIKE JANITORS AND
CLEANING PEOPLE. SO, WITH THAT,
I WILL CONCLUDE MY PRESENTATION
AND OPEN IT UP FOR QUESTIONS.
>> THANK YOU, VINCENT. THAT WAS
REALLY SUPERHERB AND A TERRIFIC
TOUR. WE HAVE A COUPLE
QUESTIONS. DO WE HAVE TIME TO
GO THROUGH THOSE?
>> WE CAN DO A FEW.
>> OKAY. QUICKLY, FROM MATTHEW
O., VINCENT HAS ANYBODY
CONSIDERED -- GAUNA IN BAT CAVES
SOUNDS NOT LIKE FUN BUT OTHERS
WOULD FIND IT EXCITING AND --
PERSIST BULK SAMPLING -- SIMILAR
TO WASTEWATER SAMPLING.
>> GOOD QUESTION. PEOPLE HAVE
DONE THAT. I VISITED A COUPLE
OF THE CASES WHICH IS INDEED
VERY INTERESTING AND PEOPLE HAVE
DONE THAT. ALTHOUGH LIKE THESE
ARE OUR VIRUSES THAT I THINK
OVERALL STABILITY IN GAUNO IS
NOT THAT HIGH. I THINK IT IS
STILL TARGETING ACTUAL BATS AND
IS PROBABLY A BETTER WAY TO GET
GOOD QUALITY SIGNATURES.
LIKE AS I SAID THESE ARE 30KB
GENOMES AND YOU ARE NOT JUST
WANTING TO DETECT PRESENCE OF
VIRUS BUT SEEING FULL GENOME AND
WHAT SPIKE LOOKS LIKE AND THAT
SAID, I THINK FOR A WHOLE NUMBER
OF PATHOGENS AND RESERVIORS,
THAT COULD BE A QUITE GOOD WAY
OF LOOKING INTO IT. WE HAVE
ACTUALLY BEEN DOING IT A LITTLE
BIT ON USING INSTANCE FECAL
ANTIBODIES IN SCAT COLLECTED
FROM WILD WESTERN LOWLAND
GORILLAS AND WHAT THEY ARE
EXPOSE TODAY AND IF THEY ARE
EXPOSED TO EBOLA AND THERE IS
LOTS OF POTENTIAL COMBINING ON
ONE END SURVEILLANCE TECHNOLOGY
WITH BETTER AND NOVEL AND MORE
SENSITIVE TOOLS TO REALLY LIKE
AS YOU SAID LIKE IT IS NOT ABOUT
LIKE ONE VIRUS AND ONE SAMPLE
BUT REALLY GET A LARGE
VIROSNAPSHOT WHAT IS CIRCULATING
IN ALL OF THE DIFFERENT BATS.
>> THANK YOU. THE OTHER
QUESTION IS FROM MARY P. ASKING
WHAT ARE X AND Y AXIS ON THE
GRAPH SHOWING EVOLUTIONARY
DISTANCE BETWEEN OMICRON AND
OTHER VARIANTS OF CONCERN?
>> THERE ARE -- THERE ARE
BASICALLY TWO FULL DILUTION
ACTION IN PRIORITIZATION ESSAY
AND THERE IS A REALLY NICE PAPER
OUT. I THINK THEY RECENTLY
PUBLISHED IT IN SCIENCE. EITHER
NATURE AND MEDICINE OR SCIENCE
TRANSLATIONAL MEDICINE AND THEY
LAY THAT NICELY OUT ANTIGENIC
EVOLUTION OF ALL OF THE VARIANTS
OF CONCERN AND THEN OMICRON BI1
AND BI2 THAT WASN'T INCLUDED IN
OUR MAP AND BR2 IS
ANTEGENERALICALLY MORE DISTANT
FROM BA1 AS WELL.
LOOK UP PAPER BY HALF MONTHS
THAT IS LAST. THEY REALLY
MAPPED IT OUT REALLY NICELY.
>> ALL RIGHT. I THINK WE BETTER
CLOSE HERE. THANKS VERY MUCH,
VINCENT.
WE ARE EXTREMELY EXCITED ABOUT
WORK YOU ARE DOING AND EXCITED
YOU ARE BACK IN THE UNITED
STATES FOR NOW. THANKS VERY
MUCH.
>>THANK YOU, STEVE.