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IT IS A PLEASURE TO INTRODUCE

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SHANE CROTTY, REMARKABLY AS AN

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UNDERGRAD HE COMBINED THIS

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TRAINING AND WRITING AHEAD OF

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THE CURVE, A BIOGRAPHY OF DAVID

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BALTIMORE.

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IF YOU GOOGLE SEARCH FOR CROTTY,

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AND BALTIMORE AND CSPAN YOU WILL

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FIND A VERY YOUNG SHANE'S 2001

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APEERPANCE ON BOOK TV TALKING

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ALL ABOUT HIS BOOK FOR 45

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MINUTES.

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SHANE NEXT DID A Ph.D. WITH

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ALSO FANTASTIC PRODUCT OF DAVID

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BALTIMORE NAMED [INDISCERNIBLE]

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STUDY AT UCSF, STUDYING POLIO

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VIRUS, STUDYING THE LONG

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STANDING PROBLEM ON HOW THE 1 OF

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THE FIRST ANTIVIRAL DRUGS WORKS.

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AND SHANE SHOWED THIS WORKS

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MOSTLY IN VIVO BY INDUCING ERROR

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CATASTROPHE IN RNA VIRUSES

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INCLUDING THE POLIO VIRUS WE'RE

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STUDYING.

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SHANE ALSO SHOWED 1 OF MY

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FAVORITE PAPERS OF HIS THAT

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QUITE REMARKABLY POLIO VIRUS IS

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ABLE TO ESCAPE THE ANTIVIRAL

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EFFECTS OF--1 OF MY FAVORITE

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DRUGS WHICH TARGETS THE HOST

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SECRETORY PATHWAY, PEOPLE SAY

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THAT TARGETING THE HOST PATHWAY,

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YOU GET AROUND THE PROBLEM OF

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VIRAL AVOIDANCE ON THE HOST AND

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SHANE SHOWED BRILLIANTLY IN THIS

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PAPER WHICH I DON'T THINK A LOT

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OF PEOPLE KNOW ABOUT, THIS IS

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JUST IS NOT TRUE, VIRUSES ARE

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VERY, VERY CLEVER.

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I HAD THE PLEASURE OF FIRST

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MEETING SHANE WHEN HE APPLIED

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FOR A POST DOC IN MY LAB.

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HE MIGHT REMEMBER MEETING

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DR. HATCHER IN HIS BATH ROBE

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WHEN WE KNOCKED ON THE WRONG

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DOOR LOOKING FOR HIS SISTER WHO

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WAS LIVING ON CAMPUS AT NIH.

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IT WAS CLEAR TO ME AT THE TIME

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THAT SHANE WAS FULLY CAPABLE OF

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BEING A PI AND I THINK I MADE

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THAT CLEAR TO SHANE.

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I HOPE I DID, THE PROMISE HE

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SHOWED WAS JUST ABSOLUTELY

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REMARKABLE.

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HE CHOSE WISELY CHOSE ON DO A

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SHORT AND HIGHLY PRODUCTIVE POST

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DOC NOD IN MY LAB, WHERE IN JUST

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2 YEARS HE BECAME AN EXPERT IN

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VIRAL IMMUNOLOGY, FOCUSING MORE

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OR LESS ON THE GENERATION OF

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MEMORY B-CELLS BUT I'M SURE HE

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GOT GREAT EXPOSURE TO T-CELLS

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WHICH [INDISCERNIBLE] LAB IS

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ALSO FAMOUS FOR.

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SHANE STARTED HIS LAB IN 2003

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AND BASICALLY BECAME A WORLD

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LEADER IN ADAPTIVE ANTIVIRAL

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UMPIRESUNITY, PHOBEUSING ON

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T-CELL BIOLOGY, PARTICULARLY IN

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THE CONTEXT OF HIV AND

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VACCINATION.

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WHEN COVID CAME ALONG, SHANE

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ALONG WITH HIS CLOSE COLLEAGUE,

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ALONG WITH ALEX [INDISCERNIBLE]

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PUBLISHED CLASSIC STUDIES OF

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HUMAN BNT RESPONSES TO

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SARS-COV-2.

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MANY OF YOU KNOW SHANE FROM HIS

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NUMBER OF APPEARANCES ON THIS

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WEEK IN VIROLOGY, IT'S A

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FANTASTIC PODCAST FROM

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[INDISCERNIBLE].

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IF YOU DON'T KNOW IT, JUST

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SEARCH FOR TWIV, AND CROTTY AND

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SHANE'S APPEARANCES ARE JUST

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FANTASTIC.

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HOW MANY TIMES HAVE YOU BEEN ON

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THERE, 4, 5?

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MANY.

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A LOT.

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IN ANY EVENT THIS IS A FANTASTIC

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FORUM FOR VIRUSES AND VIRAL

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IMMUNOLOGY AND SHANE IT'S A

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GREAT PLEASURE TO WELCOME YOU

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VIRTUALLY ANYWAY TO NIH AND I

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HOPE TO SEE YOU SOMETIME IN THE

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NEAR FUTURE IN PERSON. 

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>>THANKS FOR THAT INTRO, I

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LOVE HOW YOU MENTIONED THE VIRUS

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PAPER.

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THAT LITERALLY WAS A BET OVER A

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BEER WITH ANOTHER GRAD STUDENT

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THAT THEY WERE THE CELL

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BIOLOGIST IN THE LAB AND DOING

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GREAT WORK AND THEY JUST SAID

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IT'S IMPOSSIBLE FOR THE VIRUS TO

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ESCAPE A CELLULAR PROTEIN

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REQUIREMENT AND BET A BEER ON

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IT.

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[LAUGHTER]

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AND IT WAS DETERMINED AND TESTED

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OUT.

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I WON'T BE TALKING ABOUT THAT

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FOR THE REST OF THE DAY.

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THANKS FOR HAVING ME AND THIS IS

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A GREAT FORUM AND A FANTASTIC

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GROUP OF RESEARCHERS TO TALK TO.

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I WILL TALK ABOUT PROJECTEDS

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WE'VE DONE IN THE CONTEXT OF

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COVID, AND SOME RELATED PROJECTS

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ACTUALLY THAT REALLY GET AT

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INFORMING, SHOWING OW COVID

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VACCINE STUDIES AND COVID

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IMMUNOLOGY INFORMS OTHER

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PROGRAMS.

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I'M GOING TO START HERE WITH

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SOMETHING YOU ALL KNOW WELL BUT

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IT IS CERTAINLY INCREDIBLY

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IMPORTANT AND OUR UNDERSTANDING

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OF COVID AND OBVIOUSLY THE COVID

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VACCINES HAVE REALLY BEEN HUGE

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THINGS OVER THE PAST COUPLE OF

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YEARS.

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OUR WORK IN THIS AREA REALLY

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STARTED WITH ALEX

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[INDISCERNIBLE] EARLY IN 2020

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WHEN THERE WAS A HUGE AMOUNT OF

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SPHERE AND UNCERTAINTY ABOUT

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MOST EVERYTHING RELATED TO

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COVID-19 AND INCLUDING WHETHER

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THIS WAS A DISEASE THAT WAS A

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CONSEQUENCE OF A FACT THAT

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PEOPLE JUST DIDN'T MAKE IMMUNE

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RESPONSES OR ADAPTIVE IMMUNE

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RESPONSES TO THIS VIRUS AND/OR

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THAT PEOPLE MADE VERY UNUSUAL

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ADAPTIVE IMMUNE RESPONSES TO

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THIS VIRUS AND THOSE WERE THINGS

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THAT WE THOUGHT WE COULD

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POTENTIALLY HELP OUT WITH IN

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UNDERSTANDING AND THAT, SUCH

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UNDERSTANDING MAY BE HELPFUL FOR

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VACCINE PROGRAMS, WHICH VACCINE

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PROGRAMS WERE ALREADY UNDERWAY

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INCLUDING AMAZING EFFORTS BY THE

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VRC AND MODEL --MODERNA AND THEE

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LOTS OF CONCERNS ABOUT WHETHER

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SPIKE ALONE WAS A TARGET AND

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AGAIN, WHETHER THERE WAS SOME

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SORT OF IMMUNO DIVERGENT

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RESPONSES RELATED TO THIS VIRUS

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THAT MIGHT BE PROBLEMATIC FOR

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THIS EXAMPLE, FOR VACCINES OR IF

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WE WERE JUST GOING TO THE WRONG

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TYPE OF IMMUNE RESPONSES FOR

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THIS TYPE OF IMMUNITY.

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SO THAT WAS A SIMPLE TOPIC OF

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THIS PAPER FROM APRIL, MAY, FROM

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MAY 2020 WHERE WE SAID, WELL,

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WHAT ARE THE ADAPTIVE IMMUNE

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RESPONSES LOOK LIKE IN PEOPLE

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WITH AVERAGE CASES OF COVID-19.

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SO PEOPLE HAVE GOT INFECTED, DID

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NOT REQUIRE HOSPITALIZATION BUT

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CLEARED THE VIRUS AND PRESUMABLY

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MADE A SUCCESSFUL ADAPTIVE

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IMMUNE RESPONSE THAT CLEARED THE

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VIRUS, WHAT DID THAT IMMUNE

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RESPONSE LOOK LIKE AND IN BRIEF,

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WE SAW LIKE MULTIPLE LABS HAD

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SEEN AT THAT POINT THAT

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ESSENTIALLY ALL OF THOSE

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INDIVIDUALS MADE ANTIBODY

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RESPONSES DESPITE BUT NOTABLY

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THEY ALSO MADE CD4 T-CELL

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RESPONSES AND CD-4 T-CELL

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RESPONSES TO VIRAL PROTEINS AS

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WELL AS MANY PEOPLE HAD

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DETECTABLE REACTIONS TO THE

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RESPONSES AND THE FUNCTIONALITY

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OF THIS CELLS LOOK LIKE 1 WOULD

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EXPECT FOR A QUOTE-UNQUOTE OR

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JUST AN UNKNOWN NEW RESIRATTORY

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VIRAL INFECTION, THE

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FUNCTIONALITIES LOOK LIKE THE

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TYPES OF THINGS YOU WOULD GET IN

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AN ANTIVIRAL RESPONSE AND IN

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ADDITION SPIKE WAS AN IMMUNO

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DOMINANT TARGET OF THOSE

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RESPONSES INDICATING THAT SPHIEK

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WAS INDEED A REASONABLE CHOICE

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IF YOU WERE GOING WITH A SINGLE

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COMPONENT VACCINE AND THESE

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STUDIES HAD A VARIETY OF

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RAMIFICATIONS, CERTAINLY 1 OF

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THEM WAS--IT WAS REALLY

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INTERPRETED BY A NUMBER OF

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VACCINE MANUFACTURES THAT

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ESSENTIALLY THEY WERE ON THE

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RIGHT PATH AND THAT THEY COULD

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FOCUS THEIR EFFORTS INSTEAD OF

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TRYING MANY DIFFERENT VACCINE

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STRATEGIES, WHERE I THINK I

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COULD FOCUS ON SPIKE ONLY

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VACCINES AND TRY AND ILLICIT

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CONVENTIONAL CD4 RESPONSES IF

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00:08:05,000 --> 00:08:10,200
THEIR PLATFORMS ALLOWED.

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THE SECOND PROGRAM WE EXPLORED

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INTENSIVELY, IN THE FALL OF 2020

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THERE WAS LOTS OF FEAR AND

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UNCERTAINTY ABOUT WHETHER PEOPLE

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WOULD BE PROTECTED FROM

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REINFECTION, WERE CORONA VIRUSES

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SPECIAL IN SOME WAY AND THAT

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PEOPLE JUST DON'T DEVELOP IMMUNE

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MEMORY AND THAT WAS 1 OF THE

227
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COMMON TALKS POINTSA THE TIME

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AND WE FELT WE COULD CONTRIBUTE

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TO THAT, NOT IN TERMS OF

230
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DIRECTLY MEASURING REINFECTION

231
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RATES, RIGHT?

232
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THAT WOULD COME FROM OBVIOUSLY

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EPIDEMIOLOGICAL STUDIES BUT BY

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DIRECT MEASUREMENTS OF IMMUNE

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MEMORY TO A PRIMARY VIRAL

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INFECTION IN HUMANS AND SEE WHAT

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IT WOULD LOOK LIKE AND THAT WAS

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PUBLISHED IN THIS STUDY WHICH

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WAS POSTED ONLINE AROUND

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THANKSGIVING 2020.

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WE HAD A LAB PARTY RECENTLY

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WHERE SOMEBODY MADE A VERY NERDY

243
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CAKE FOR THE LAB THAT HAD LAB

244
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PAPER QR CODES PRINTED ALL OVER

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IT AND I WAS LIKE, IT WAS REALLY

246
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UNEXPECTED, AND THEY'RE LIKE OH

247
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YEAH, THIS IS A THING NOW, YOU

248
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DO IT WITH YOUR SLIDESSA THE

249
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SEMINAR AND YOU HAVE THE QR CODE

250
00:09:21,760 --> 00:09:23,440
IN SEMINAR AND SO THERE YOU GO

251
00:09:23,440 --> 00:09:26,800
AND I'M TRYING IT OUT AND IT'S

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IN QR CODE.

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A CRITICAL PROBLEM WITH IMMUNE

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MEMORY GOING BACK TO MY DAYS IN

255
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[INDISCERNIBLE] LAB AND MANY

256
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OTHER LABS BEFORE IT SHANKAR IT

257
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IS QUITE HARD TO PREDICT IMMUNE

258
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MEMORY AND SO A FOCUS FOR US WAS

259
00:09:42,280 --> 00:09:44,960
TO WAIT UNTIL 6-8 MONTHS POST

260
00:09:44,960 --> 00:09:46,880
INFECTION SO WE CAN GET A SENSE

261
00:09:46,880 --> 00:09:48,040
OF THE CONNECTED IMMUNE MEMORY

262
00:09:48,040 --> 00:09:49,440
AND REALLY TAKING THE APPROACH

263
00:09:49,440 --> 00:09:51,480
WE'VE TAKEN IN ALMOST ALL OF OUR

264
00:09:51,480 --> 00:09:52,800
STUDIES IS REALLY A WHOLISTIC

265
00:09:52,800 --> 00:09:56,200
LOOK AT THE ADAPTIVE IMMUNE

266
00:09:56,200 --> 00:09:56,640
RESPONSES.

267
00:09:56,640 --> 00:09:57,360
CERTAINLY MEASURING ANTIBODIES

268
00:09:57,360 --> 00:09:59,360
AND ALSO MEASURING THE OTHER

269
00:09:59,360 --> 00:10:00,840
MAJOR COMPONENTS OF ADANTE

270
00:10:00,840 --> 00:10:02,760
FOWLERRIVE IMMUNITY WHICH WOULD

271
00:10:02,760 --> 00:10:05,640
BE MEMORY B-CELLS, MEMORY CD4S

272
00:10:05,640 --> 00:10:07,600
AND MEMORY CD8S AND ACROSS

273
00:10:07,600 --> 00:10:09,640
MULTIPETRESSABLE ANTIGENS AND

274
00:10:09,640 --> 00:10:11,840
WHEN WE DID THAT, WE SAW THAT

275
00:10:11,840 --> 00:10:14,360
PEOPLE DID DEVELOP ENHANCED

276
00:10:14,360 --> 00:10:21,160
MEMORY AFTER INFECTION AND BY

277
00:10:21,160 --> 00:10:22,360
WAITING UNTIL APPROXIMATELY 8

278
00:10:22,360 --> 00:10:23,080
MONTHS POST INFECTION, WE BEING

279
00:10:23,080 --> 00:10:25,640
SEE WHAT THE KINETETTICS OF

280
00:10:25,640 --> 00:10:26,600
THOSE RESPONSES ARE AND ON THE

281
00:10:26,600 --> 00:10:28,400
LEFT HERE WE HAVE ANTIBODY

282
00:10:28,400 --> 00:10:29,960
TITERS AND THESE WERE REPORTED

283
00:10:29,960 --> 00:10:37,880
BY MULTIPLE  LABS AT THE TIME

284
00:10:37,880 --> 00:10:39,400
WHICH ARE THAT ANTIBODIES ARE

285
00:10:39,400 --> 00:10:41,320
RELATIVELY LOW AND AFFECT PEOPLE

286
00:10:41,320 --> 00:10:45,240
BUT SOMETHING LIKE 90-98% OF

287
00:10:45,240 --> 00:10:46,400
PEOPLE DO BECOME ANTIBODY

288
00:10:46,400 --> 00:10:48,280
POSITIVE AND THOSE TITERS DROP

289
00:10:48,280 --> 00:10:50,120
OVER A RELATIVELY SHORT TIME

290
00:10:50,120 --> 00:10:52,680
FRAME BUT BY 6 MONTHS ARE REALLY

291
00:10:52,680 --> 00:10:53,600
RATHER STABLE AND INDEED THEIR

292
00:10:53,600 --> 00:10:55,040
DATA IN THE LITERATURE NOW OUT

293
00:10:55,040 --> 00:11:00,320
TO A YEAR AND A HALF OR 2 YEARS

294
00:11:00,320 --> 00:11:02,520
SEEING THESE INFECTION INDUCED

295
00:11:02,520 --> 00:11:04,240
ANTIBODY TITERS ARE TABLELY

296
00:11:04,240 --> 00:11:05,360
MAINTAINED AND WHAT WE WERE

297
00:11:05,360 --> 00:11:08,040
ADDING TO THAT LITERATURE WAS

298
00:11:08,040 --> 00:11:10,960
REALLY THE CELLULAR ASPECTS, THE

299
00:11:10,960 --> 00:11:14,880
MEMORY B-CELLS, THE CD8 T-CELLS

300
00:11:14,880 --> 00:11:17,080
AND CD4 T-CELLINGS AND PROBABLY

301
00:11:17,080 --> 00:11:18,240
THE MOST SURPRISING FINDING WAS

302
00:11:18,240 --> 00:11:21,000
THAT PEOPLE HAVE MORE MEMORY

303
00:11:21,000 --> 00:11:23,080
B-CELLS POST INFECTION AND AT 1

304
00:11:23,080 --> 00:11:25,080
MONTH POST INFECTION TO FOLLOW

305
00:11:25,080 --> 00:11:26,160
THE OPPOSITE KINETICS OF THE

306
00:11:26,160 --> 00:11:28,000
ANTIBODY RESPONSE AND WE SAW

307
00:11:28,000 --> 00:11:30,560
THIS FOR SPIKE RBD AND

308
00:11:30,560 --> 00:11:31,960
NUCLEOCAPSID AND THIS IS

309
00:11:31,960 --> 00:11:33,600
REPRODUCED BY MULTIPLE LABS.

310
00:11:33,600 --> 00:11:37,040
AND THAT THE KINETICS AND T-CELL

311
00:11:37,040 --> 00:11:39,000
MEMORY WAS DIFFERENT FROM THE

312
00:11:39,000 --> 00:11:41,240
KINETICS OF MEMORY B-CELLS AND

313
00:11:41,240 --> 00:11:43,240
OF SERUM ANTIBODIES SO THESE

314
00:11:43,240 --> 00:11:44,160
DIFFERENT COMPONENTS OF IMMUNE

315
00:11:44,160 --> 00:11:47,840
MEMORY DO NOT ALL FOLLOW THE

316
00:11:47,840 --> 00:11:50,400
SAME KINETICS AND THAT FOR CD8S

317
00:11:50,400 --> 00:11:52,960
ABOUT 70% OF PEOPLE HAD

318
00:11:52,960 --> 00:11:54,160
DETECTABLE RESPONSES EARLY,

319
00:11:54,160 --> 00:11:57,360
ABOUT 50% AT 8 MONTHS, BUT OF

320
00:11:57,360 --> 00:11:58,160
THE DETECTABLE RESPONSES THE

321
00:11:58,160 --> 00:12:00,400
HALF LIFE OF THOSE RESPONSES WAS

322
00:12:00,400 --> 00:12:03,360
ABOUT 125 DAYS, WHICH ACTUALLY

323
00:12:03,360 --> 00:12:05,080
MATCHED WHAT [INDISCERNIBLE] HAD

324
00:12:05,080 --> 00:12:12,000
DEFINED EARLIER FOR THE YELLOW

325
00:12:12,000 --> 00:12:20,480
FEVER VIRUS VACCINE WHICH IS A

326
00:12:20,480 --> 00:12:21,720
RESPONSE TO INFECTION LOOKED

327
00:12:21,720 --> 00:12:23,520
LIKE IT WOULD BE QUITE GOOD IN

328
00:12:23,520 --> 00:12:26,480
TERMS OF THE QUALITY OF DURATION

329
00:12:26,480 --> 00:12:28,600
EMPLOY THE CD4 RESPONSE TO THIS

330
00:12:28,600 --> 00:12:30,360
VIRUS ARE QUITE ROBUST, ALMOST A

331
00:12:30,360 --> 00:12:32,800
HUNDRED% OF PEOPLE WERE POSITIVE

332
00:12:32,800 --> 00:12:35,000
INITIALLY AND 98% OF PEOPLE

333
00:12:35,000 --> 00:12:36,760
POSITIVE AT 6-8 MONTHS WITH THE

334
00:12:36,760 --> 00:12:39,240
A SIMILAR HALF LIFE SUGGESTING

335
00:12:39,240 --> 00:12:41,240
THAT THE CD4 AND 8 MEMORY WOULD

336
00:12:41,240 --> 00:12:42,600
BE LONG LASTING.

337
00:12:42,600 --> 00:12:44,320
THERE WAS BT ANY BENCHMARK IN

338
00:12:44,320 --> 00:12:46,800
THE LITERATURE FOR LOOKING AT

339
00:12:46,800 --> 00:12:49,480
KINETICS OF CD4 T-CELL MEMORY TO

340
00:12:49,480 --> 00:12:52,720
A PRIMARY HUMAN INFECTION.

341
00:12:52,720 --> 00:12:56,360
SO THIS IS ACTUALLY NOW A

342
00:12:56,360 --> 00:12:58,120
PRIMARY REFERENCE POINT FOR THE

343
00:12:58,120 --> 00:12:59,640
FIELD FOR WHAT IMMUNE MEMORY

344
00:12:59,640 --> 00:13:02,960
LOOKS LIKE IN THE CD4 T-CELL

345
00:13:02,960 --> 00:13:04,640
COMPARTMENT TO A VIRAL INFECTION

346
00:13:04,640 --> 00:13:09,400
AND IN FACT, OVERALL, THIS WAS A

347
00:13:09,400 --> 00:13:10,720
VERY LARGE STUDY IN TERMS OF

348
00:13:10,720 --> 00:13:12,160
LOOKING AT MEMORY TO ALL OF

349
00:13:12,160 --> 00:13:13,800
THESE COMPONENTS AND PROBABLY

350
00:13:13,800 --> 00:13:17,840
THE LARGEST STUDY BEFORE THAT TO

351
00:13:17,840 --> 00:13:19,960
AN ACUTE INFECTION WAS PROBABLY

352
00:13:19,960 --> 00:13:21,320
ABOUT 3 OR 4 INDIVIDUALS AND IN

353
00:13:21,320 --> 00:13:23,280
THIS STUDY WE HAD 188.

354
00:13:23,280 --> 00:13:26,640
I WILL SAY JULIE [INDISCERNIBLE]

355
00:13:26,640 --> 00:13:27,920
AND [INDISCERNIBLE] HAD A

356
00:13:27,920 --> 00:13:30,000
SIMILAR STUDY PUBLISHED I THINK

357
00:13:30,000 --> 00:13:31,560
6 MONTHS LATER AND I THINK THEY

358
00:13:31,560 --> 00:13:35,320
DID A NICER JOB OF CALCULATING

359
00:13:35,320 --> 00:13:37,080
HALF LIVES, WHERE INITIALLY THE

360
00:13:37,080 --> 00:13:39,480
HALF LIVES LOOK LIKE THIS AND

361
00:13:39,480 --> 00:13:40,840
THEY PROBABLY PLATEAU OR NEARLY

362
00:13:40,840 --> 00:13:42,800
PLATEAU THAT THE HALF LIVES

363
00:13:42,800 --> 00:13:44,240
PROBABLY BECOME MORE LIKE A YEAR

364
00:13:44,240 --> 00:13:45,760
AT THESE LATER TIME POINTS AND

365
00:13:45,760 --> 00:13:47,520
IT WOULD BE GOOD TO SEE FURTHER

366
00:13:47,520 --> 00:13:49,960
FOLLOW UP ON THOSE, BUT

367
00:13:49,960 --> 00:13:51,000
ALTOGETHER, THE RESULTS

368
00:13:51,000 --> 00:13:52,400
INDICATED THERE WAS SUBSTANTIAL

369
00:13:52,400 --> 00:13:53,400
IMMUNE MEMORY AFTER THIS

370
00:13:53,400 --> 00:13:56,480
INFECTION, AND IT WAS PROBABLY

371
00:13:56,480 --> 00:13:57,840
SUFFICIENT IMMUNE MEMORY TO

372
00:13:57,840 --> 00:14:02,480
PROVIDE PROTECTION AT LEAST FROM

373
00:14:02,480 --> 00:14:03,080
SERIOUS SARS-COV-2 INFECTIONS

374
00:14:03,080 --> 00:14:04,160
FOR YEARS INTO THE FUTURE, THIS

375
00:14:04,160 --> 00:14:06,520
IS BEFORE THE EXISTENCE OF

376
00:14:06,520 --> 00:14:07,920
VARIANTS WHICH IS DIRECTLY

377
00:14:07,920 --> 00:14:10,360
LOOKING AT IMMUNE MEMORY AND IN

378
00:14:10,360 --> 00:14:14,400
FACT LOOKING AT EPIDEMIOLOGICAL

379
00:14:14,400 --> 00:14:15,200
STUDIES HAVE SUPPORTED THAT OVER

380
00:14:15,200 --> 00:14:16,960
AND OVER AGAIN AT THIS POINT.

381
00:14:16,960 --> 00:14:18,800
AND JOHN MENTIONED WHAT WOULD

382
00:14:18,800 --> 00:14:20,760
HAPPEN IF YOU GOOGLED MY NAME

383
00:14:20,760 --> 00:14:22,520
AND CSPAN IN BALTIMORE.

384
00:14:22,520 --> 00:14:30,360
IF YOU GOOGLE MY NAME AND CSPAN,

385
00:14:30,360 --> 00:14:33,520
YOU WILL FIND DIFFERENT HITS

386
00:14:33,520 --> 00:14:35,240
INVOLVING INTERESTING DEBATES

387
00:14:35,240 --> 00:14:37,120
RELATING INTERPRETING TO THIS

388
00:14:37,120 --> 00:14:39,720
DATA WHICH INCLUDED SENATOR RAND

389
00:14:39,720 --> 00:14:42,800
PAUL AND TONY FAUCI AMONGST

390
00:14:42,800 --> 00:14:44,600
OTHERS BUT THAT'S A TOPIC FOR

391
00:14:44,600 --> 00:14:44,920
ANOTHER DAY.

392
00:14:44,920 --> 00:14:50,200
WITH ALL OF THAT ESSENTIALLY AS

393
00:14:50,200 --> 00:14:52,600
BACKGROUND, WE THEN MOVE TO

394
00:14:52,600 --> 00:14:57,040
UNDERSTAND IMMUNE MEMORY TO

395
00:14:57,040 --> 00:14:57,520
COVID-19 VACCINES.

396
00:14:57,520 --> 00:14:59,000
AND FOR NOW I WILL TALK THROUGH

397
00:14:59,000 --> 00:15:03,560
THE WORK WE PUBLISHED EARLIER

398
00:15:03,560 --> 00:15:05,720
THIS YEAR WHICH WAS THE FIRST

399
00:15:05,720 --> 00:15:07,680
PUBLICATION TO LOOK AT

400
00:15:07,680 --> 00:15:08,800
HEAD-TO-HEAD COMPARISON TO

401
00:15:08,800 --> 00:15:12,040
IMMUNE MEMORY TO 4 COVID-19

402
00:15:12,040 --> 00:15:15,840
VACCINES, INCLUDING A PROTEIN

403
00:15:15,840 --> 00:15:18,200
VACCINE TO LOOK AT IMMUNE MEMORY

404
00:15:18,200 --> 00:15:19,840
OUT AT LEAST 6 MONTHS WHERE WE

405
00:15:19,840 --> 00:15:21,160
FEEL LIKE WE REALLY DO HAVE TO

406
00:15:21,160 --> 00:15:23,000
WAIT THAT LONG TO GET A SENSE OF

407
00:15:23,000 --> 00:15:23,880
WHAT MEMORY'S LOOKING LIKE AND

408
00:15:23,880 --> 00:15:25,840
TO DO SO AGAIN IN A RELATIVELY

409
00:15:25,840 --> 00:15:27,800
WHOLISTIC WAY OF LOOKING AT ALL

410
00:15:27,800 --> 00:15:32,320
3 MAJOR BRANCHES OF ADAPTIVE

411
00:15:32,320 --> 00:15:33,480
IMMUNITY, THE HUMORAL IMMUNITY

412
00:15:33,480 --> 00:15:36,320
AS WELL AS CD4 AND 8 T-CELLS AND

413
00:15:36,320 --> 00:15:38,360
WE FELT LIKE THESE WERE KEY

414
00:15:38,360 --> 00:15:40,400
COMPARISONS TO DO FOR

415
00:15:40,400 --> 00:15:41,680
UNDERSTANDING WHY ARE THERE

416
00:15:41,680 --> 00:15:43,720
SIMILAR OR DIFFERENT OUTCOMES

417
00:15:43,720 --> 00:15:45,120
WITH DIFFERENT COVID-19 VACCINE

418
00:15:45,120 --> 00:15:46,240
PLATFORMS AND ALSO FOR LOOKING

419
00:15:46,240 --> 00:15:51,040
INTO THE FUTURE, LOOKING TO THE

420
00:15:51,040 --> 00:15:53,800
FUTURE FOR VACCINE DEVELOPMENT

421
00:15:53,800 --> 00:15:54,840
TO OTHER PATHOGENS.

422
00:15:54,840 --> 00:15:57,640
ARE SOME OF THESE PLATFORMS MORE

423
00:15:57,640 --> 00:16:02,720
SUITED TO SOME PATHOGENS THAN

424
00:16:02,720 --> 00:16:06,560
OTHERS FOR EXAMPLE, OR IS--OR

425
00:16:06,560 --> 00:16:07,600
RNA VACCINES ESSENTIALLY

426
00:16:07,600 --> 00:16:11,040
MIRACULOUS, THAT THEY DID

427
00:16:11,040 --> 00:16:12,320
SOMETHING PHENOMENAL THAT REALLY

428
00:16:12,320 --> 00:16:14,080
CONVENTIONAL OR MORE

429
00:16:14,080 --> 00:16:15,040
CONVENTIONAL VACCINE

430
00:16:15,040 --> 00:16:18,560
TECHNOLOGIES COULD NOT.

431
00:16:18,560 --> 00:16:20,800
THOSE WERE STILL OPEN QUESTIONS

432
00:16:20,800 --> 00:16:21,600
FROM AN IMMUNOLOGICAL

433
00:16:21,600 --> 00:16:24,200
PERSPECTIVE BECAUSE IT IS HARD

434
00:16:24,200 --> 00:16:25,920
TO RECRUIT PEOPLE WHOF GOTTEN

435
00:16:25,920 --> 00:16:27,200
EACH OF THESE DIFFERENT VACCINES

436
00:16:27,200 --> 00:16:28,800
AND PARTICULARLY FROM A T-CELL

437
00:16:28,800 --> 00:16:30,760
SIDE, YOU HAVE TO BE DOING THOSE

438
00:16:30,760 --> 00:16:33,240
ASSAYS IN THE SAME LAB FOR THEM

439
00:16:33,240 --> 00:16:39,160
TO BE COMPARABLE AND IN

440
00:16:39,160 --> 00:16:40,840
ADDITION, WE HAD LOCAL INFECTED

441
00:16:40,840 --> 00:16:47,120
INDIVIDUALS SO THAT WE CAN

442
00:16:47,120 --> 00:16:48,440
COMPARE VACCINE ILLICITTED

443
00:16:48,440 --> 00:16:48,880
IMMUNE MEMORY.

444
00:16:48,880 --> 00:16:52,560
SO WHAT DID ALL OF THAT LOOK

445
00:16:52,560 --> 00:16:52,760
LIKE?

446
00:16:52,760 --> 00:16:55,800
HERE'S THE WAY WE STRUCTURED THE

447
00:16:55,800 --> 00:16:57,360
FIGURURES, WE DID ANTIBODIES,

448
00:16:57,360 --> 00:17:00,520
AND THEN EACH OF THESE OTHER

449
00:17:00,520 --> 00:17:01,720
IMMUNE COMPONENTS AND IN HERE

450
00:17:01,720 --> 00:17:03,200
WE'RE SHOWING THE RESPONSES TO

451
00:17:03,200 --> 00:17:06,120
EACH OF THE VACCINES SO MODEL

452
00:17:06,120 --> 00:17:08,840
CITIZEN BERNEA, PFIZER, J& 
J

453
00:17:08,840 --> 00:17:12,240
AND NOVAVAX, AND AT THE DOSES

454
00:17:12,240 --> 00:17:14,080
AND TIMING AND USE IN THE UNITED

455
00:17:14,080 --> 00:17:17,080
STATES AND I'M SORRY, I SHOULD

456
00:17:17,080 --> 00:17:18,320
HAVE BEEN CLEAR--FOR ANYBODY

457
00:17:18,320 --> 00:17:23,440
WHO'S NOT FAMILIAR WITH THE

458
00:17:23,440 --> 00:17:25,520
NOVAVAX VACCINE, NOVAVAX IS A

459
00:17:25,520 --> 00:17:32,440
RECOMBIN ANT SPIKE PROTEIN WITH

460
00:17:32,440 --> 00:17:33,200
[INDISCERNIBLE] ADJUVANT AND IT

461
00:17:33,200 --> 00:17:35,200
SERVES AS A USEFUL COMPARISON

462
00:17:35,200 --> 00:17:38,040
HERE BECAUSE THERE'S A HUNDRED

463
00:17:38,040 --> 00:17:40,640
YEARS MORE EXPERIENCE WITH

464
00:17:40,640 --> 00:17:42,640
PROTEIN BASED VACCINES THAN RNA

465
00:17:42,640 --> 00:17:47,240
VACCINES AND SO, PROVIDES A

466
00:17:47,240 --> 00:17:47,880
VALUABLE COMPARISON.

467
00:17:47,880 --> 00:17:49,920
ONE, CAVEAT TO THIS IS THAT WE

468
00:17:49,920 --> 00:17:53,840
WERE NOT ABLE TO RECRUIT THESE

469
00:17:53,840 --> 00:17:54,720
INDIVIDUALS IMMEDIATELY AFTER

470
00:17:54,720 --> 00:17:55,840
IMMUNIZATION, SO WE ONLY HAVE

471
00:17:55,840 --> 00:17:58,680
THE MEMORY TIME POINTS FOR THE

472
00:17:58,680 --> 00:18:00,520
NOVAVAX INDIVIDUALS.

473
00:18:00,520 --> 00:18:03,360
T1 WOULD BE PREVACCINATION.

474
00:18:03,360 --> 00:18:05,720
T2 IS AFTER A FIRST VACCINATION

475
00:18:05,720 --> 00:18:07,960
IN THE CONTEXT OF THE RNA

476
00:18:07,960 --> 00:18:11,280
VACCINES, T3 AND 2 WEEKS AFTER

477
00:18:11,280 --> 00:18:12,240
THE SECOND IMMUNIZATION, T4

478
00:18:12,240 --> 00:18:14,040
WOULD BE 3 MONTHS OUT AND T5

479
00:18:14,040 --> 00:18:15,560
WOULD BE 6 MONTHS OUT

480
00:18:15,560 --> 00:18:19,280
APPROXIMATELY FOR EACH OF THESE,

481
00:18:19,280 --> 00:18:19,720
OKAY?

482
00:18:19,720 --> 00:18:22,160
AND THEN THE THICK LINES IN EACH

483
00:18:22,160 --> 00:18:24,080
CASE WHICH YOU CAN FOCUS ON ARE

484
00:18:24,080 --> 00:18:25,920
THE GMEs OF THE ENTIRE COHORT,

485
00:18:25,920 --> 00:18:27,560
AND THEN WE HAVE CONVENIENT

486
00:18:27,560 --> 00:18:28,880
REFERENCE OVER HERE FOR HOW DOES

487
00:18:28,880 --> 00:18:33,360
THIS ALL COMPARE TO INFECTED

488
00:18:33,360 --> 00:18:34,000
INDIVIDUALS.

489
00:18:34,000 --> 00:18:34,840
SO INFECTED INDIVIDUALS ARE

490
00:18:34,840 --> 00:18:38,840
BEING SHOWN IN YELLOW WITH THE

491
00:18:38,840 --> 00:18:40,240
SAME COLOR CODES FOR THE

492
00:18:40,240 --> 00:18:40,840
VACCINES OVER HERE.

493
00:18:40,840 --> 00:18:42,360
SO IN TERMS OF ANTIBODY

494
00:18:42,360 --> 00:18:43,880
RESPONSES THIS WORK WAS DONE IN

495
00:18:43,880 --> 00:18:47,840
THE GROUP BY POST DOCTORAL

496
00:18:47,840 --> 00:18:50,320
FELLOWS ZALI ZHANG, AND

497
00:18:50,320 --> 00:18:54,160
ASSISTANT PROFESSOR AT UCSD GEN

498
00:18:54,160 --> 00:18:56,760
DAN AND WE CAPITULATED THAT THE

499
00:18:56,760 --> 00:18:59,640
VACCINES ARE FANTASTIC AT

500
00:18:59,640 --> 00:19:02,640
ILLICITTING HIGH ANTIBODY TITERS

501
00:19:02,640 --> 00:19:03,440
QUICKLY AND CONSISTENTLY ACROSS

502
00:19:03,440 --> 00:19:05,240
INDIVIDUALS BUT WITH A PRETTY

503
00:19:05,240 --> 00:19:07,720
DRAMATIC DECAY OVER A 6 MONTH

504
00:19:07,720 --> 00:19:09,160
PERIOD OF TIME AND TO ME THE

505
00:19:09,160 --> 00:19:11,280
BEST DAT I'VE SEEN IS THAT THOSE

506
00:19:11,280 --> 00:19:13,200
REALLY CONTINUED TO DECAY FOR 10

507
00:19:13,200 --> 00:19:21,840
MONTHS AFTER 2 DOSES OF RNA

508
00:19:21,840 --> 00:19:22,040
VACCINE.

509
00:19:22,040 --> 00:19:25,480
AND ACTUALLY OUT AT 6 MONTHS THE

510
00:19:25,480 --> 00:19:28,040
NOVAVAX PROTEIN HAS NEUTRALIZING

511
00:19:28,040 --> 00:19:29,200
ANTIBODY TITERS QUITE COMPARABLE

512
00:19:29,200 --> 00:19:32,320
TO MODEL CITIZEN DERNA AND

513
00:19:32,320 --> 00:19:34,760
PFIZER WHICH ARE SIGNIFICANTLY

514
00:19:34,760 --> 00:19:37,080
HIGHER THAN WHAT 1 GETS AFTER

515
00:19:37,080 --> 00:19:40,920
INFECTION OR AFTER A SINGLE DOSE

516
00:19:40,920 --> 00:19:41,160
J&  J.

517
00:19:41,160 --> 00:19:43,600
NOW NOTE ABLE I WAS INCREEINGING

518
00:19:43,600 --> 00:19:45,160
ABOUT THE J&  J VACCINE AND

519
00:19:45,160 --> 00:19:46,640
OTHER GROUPS HAVE NOTED THIS AS

520
00:19:46,640 --> 00:19:50,880
WELL IS THAT AT A MONTH POST

521
00:19:50,880 --> 00:19:53,000
VACCINATION, IT'S REALLY

522
00:19:53,000 --> 00:19:54,120
RELATIVELY POOR NEUTRALIZING

523
00:19:54,120 --> 00:19:55,800
ANTIBODY TITERS, IT'S ONLY ABOUT

524
00:19:55,800 --> 00:19:59,520
50% OF PEOPLE HAVE TITERS THAT

525
00:19:59,520 --> 00:20:03,560
ARE ABOVE 20 BUT INTRIGUINGLY

526
00:20:03,560 --> 00:20:04,440
THOSE TITERS INCREASE OVER TIME

527
00:20:04,440 --> 00:20:09,520
AND AS A COHORT PEOPLE HAVE

528
00:20:09,520 --> 00:20:13,960
HIGHER AN AVERAGE NEUTRALIZING

529
00:20:13,960 --> 00:20:15,600
TITERS AT 1 MONTH THAN THEY DID

530
00:20:15,600 --> 00:20:16,360
AT 6 MONTHS.

531
00:20:16,360 --> 00:20:19,040
WHICH IS THE TREND YOU GET WITH

532
00:20:19,040 --> 00:20:20,600
RNA VACCINES INDICATING THESE

533
00:20:20,600 --> 00:20:24,760
VACCINE PLATFORMS ARE ENGAGING

534
00:20:24,760 --> 00:20:27,960
DIFFERENT IMMUNOLOGICAL

535
00:20:27,960 --> 00:20:28,760
MECHANISMS OF ACTION.

536
00:20:28,760 --> 00:20:31,880
IF WE LOOK AT CD4 T-CELL

537
00:20:31,880 --> 00:20:34,040
RESPONSES WE SEE THAT THE RNA

538
00:20:34,040 --> 00:20:37,280
VACCINES ARE VERY GOOD AT

539
00:20:37,280 --> 00:20:38,160
ELUCIDATING ROBUST RESPONSES

540
00:20:38,160 --> 00:20:41,080
BOTH ACUTE AND OUT AT MEMORY

541
00:20:41,080 --> 00:20:42,120
TIME POINTS.

542
00:20:42,120 --> 00:20:43,440
SIX MONTHS BOTH VACCINATION,

543
00:20:43,440 --> 00:20:44,760
THERE'S REALLY LESS THAN A 2

544
00:20:44,760 --> 00:20:46,800
FOLD DECLINE IN THE MAGNITUDE OF

545
00:20:46,800 --> 00:20:49,160
THE SPIKE SPECIFIC CD4 T-CELLS

546
00:20:49,160 --> 00:20:50,400
WHICH IS REALLY QUITE IMPRESSIVE

547
00:20:50,400 --> 00:20:55,800
IN MY OPINION FOR THE R NA

548
00:20:55,800 --> 00:20:58,240
VACCINES AND IN FACT, THEY

549
00:20:58,240 --> 00:21:00,000
RECEIVED HIGHER CD4 RESPONSES

550
00:21:00,000 --> 00:21:00,800
THAN INFECTION.

551
00:21:00,800 --> 00:21:02,920
NOW INFECTION ALSO ILLICITS

552
00:21:02,920 --> 00:21:05,160
T-CELL RESPONSES TO OTHER

553
00:21:05,160 --> 00:21:05,520
ANTIGENS, RIGHT?

554
00:21:05,520 --> 00:21:07,280
BESIDES SPIKE, BUT STILL IF YOU

555
00:21:07,280 --> 00:21:08,320
SPECIFICALLY FOCUS ON SPIKE,

556
00:21:08,320 --> 00:21:12,000
THESE ARE STILL PRETTY

557
00:21:12,000 --> 00:21:13,480
IMPRESSIVE RESPONSES AND REALLY

558
00:21:13,480 --> 00:21:16,880
THE RNA VACCINE RESPONSES ARE IN

559
00:21:16,880 --> 00:21:22,400
LINE WITH THE NOVA VAX AND IT

560
00:21:22,400 --> 00:21:25,000
CAN DO WELL AT ILLICITTING

561
00:21:25,000 --> 00:21:26,200
RESPONSES IN COMPARISON TO RNA

562
00:21:26,200 --> 00:21:28,240
AND IN OUR HANDS WITH THESE

563
00:21:28,240 --> 00:21:29,800
TYPES OF ASSAYS ACTUALLY J& 
J

564
00:21:29,800 --> 00:21:31,880
WAS THE LOWEST OF THE RESPONDERS

565
00:21:31,880 --> 00:21:34,320
WHICH REALLY CONTRAST WITH

566
00:21:34,320 --> 00:21:35,400
INITIAL EXPECTATIONS THAT A

567
00:21:35,400 --> 00:21:37,760
VIRAL VECTOR WOULD BE THE BEST

568
00:21:37,760 --> 00:21:39,240
AT ILLICITTING T-CELL RESPONSES

569
00:21:39,240 --> 00:21:42,400
SO AT LEAST WITH CD4S, WE DID

570
00:21:42,400 --> 00:21:45,040
NOT FIND THAT TO BE THE CASE BY

571
00:21:45,040 --> 00:21:48,840
ANY OF THESE METRICS ALTHOUGH IT

572
00:21:48,840 --> 00:21:51,240
CERTAINLY DID ILLICIT CD4

573
00:21:51,240 --> 00:21:54,440
RESPONSES AT 4 AND 6 MONTHS.

574
00:21:54,440 --> 00:21:56,680
WE DID BREAK THIS DOWN INTO

575
00:21:56,680 --> 00:21:57,960
INDIVIDUAL CYTOKINES AND I WILL

576
00:21:57,960 --> 00:22:00,840
HEIGHT LIGHT WE WERE INTRIGUED

577
00:22:00,840 --> 00:22:06,360
THAT THERE ARE A NUMBER OF

578
00:22:06,360 --> 00:22:08,440
GRANZYME B CD4 CELLS ILLICITTED

579
00:22:08,440 --> 00:22:11,120
BY EACH OF THESE 4 VACCINE

580
00:22:11,120 --> 00:22:12,960
PLATFORMS IN HUMANS WHICH WASN'T

581
00:22:12,960 --> 00:22:16,880
NECESSARILY WHAT WE EXPECTED TO

582
00:22:16,880 --> 00:22:17,280
SEE.

583
00:22:17,280 --> 00:22:18,200
OF KEY IMPORTANCE, IS THE

584
00:22:18,200 --> 00:22:23,160
ABILITY OF THESE VACCINES TO

585
00:22:23,160 --> 00:22:25,160
ILLICIT TFH CELLS, THEY ARE THE

586
00:22:25,160 --> 00:22:26,960
SUBSET OF CD4s THAT ARE

587
00:22:26,960 --> 00:22:31,000
REQUIRED FOR HELPING B-CELLS AND

588
00:22:31,000 --> 00:22:33,040
THEY'RE REQUIRED FOR THE

589
00:22:33,040 --> 00:22:34,960
MAJORITY OF NEUTRALIZING

590
00:22:34,960 --> 00:22:37,400
ANTIBODY RESPONSES TO SARS-COV-2

591
00:22:37,400 --> 00:22:41,640
AND THEY'RE CERTAINLY REQUIRED

592
00:22:41,640 --> 00:22:44,480
FOR ALL OF THE OMICRON

593
00:22:44,480 --> 00:22:46,440
ANTIBODIES HAVE YOU CIRCULATING

594
00:22:46,440 --> 00:22:48,080
IN YOUR BLOOD WHICH ARE THE

595
00:22:48,080 --> 00:22:50,280
SOURCE OF--WHICH ARE THE PRODUCT

596
00:22:50,280 --> 00:22:52,720
OF GERMINAL CENTERS AND AFFINITY

597
00:22:52,720 --> 00:22:54,000
MATURATION WHICH WE WILL COME

598
00:22:54,000 --> 00:22:55,320
BACK TO LATER.

599
00:22:55,320 --> 00:22:57,240
SO THESE CELLS ARE CRITICAL.

600
00:22:57,240 --> 00:22:58,680
THEY'RE NOT GENERALLY AT HIGH

601
00:22:58,680 --> 00:23:00,080
FREQUENCIES IN THE BLOOD BUT

602
00:23:00,080 --> 00:23:02,720
THEY ARE DETECTABLE AND SO WE'RE

603
00:23:02,720 --> 00:23:04,600
ABLE TO SEE THAT THE RNA

604
00:23:04,600 --> 00:23:06,040
VACCINES GENERATE THESE AND

605
00:23:06,040 --> 00:23:07,320
GENERATED THEM WELL, GENERATED

606
00:23:07,320 --> 00:23:10,240
THEM EVEN A BIT BETTER THAN
J& 

607
00:23:10,240 --> 00:23:14,040
J AND IN LINE WITH NOVA VAX, AND

608
00:23:14,040 --> 00:23:17,800
I WOULD ACTUALLY CONCLUDE THAT I

609
00:23:17,800 --> 00:23:21,080
THINK THAT THE POTENCY OF RNA

610
00:23:21,080 --> 00:23:22,400
VACCINES FOR ILLICITTING

611
00:23:22,400 --> 00:23:24,240
NEUTRALIZING ANTIBODIES AND

612
00:23:24,240 --> 00:23:25,800
BEING SO HAWAIILY PROTECTIVE SO

613
00:23:25,800 --> 00:23:27,240
QUICKLY REALLY COMES DOWN TO

614
00:23:27,240 --> 00:23:29,080
THEIR ABILITY, THEIR IMPRESSIVE

615
00:23:29,080 --> 00:23:32,760
ABILITY TO PRIME CD4 T-CELL

616
00:23:32,760 --> 00:23:34,520
RESPONSES AND DRIVE TFH CELL

617
00:23:34,520 --> 00:23:35,480
DIFFERENTIATION AND I THINK

618
00:23:35,480 --> 00:23:36,560
WE'RE SHOWING THAT HERE.

619
00:23:36,560 --> 00:23:38,560
IN ADDITION TO GENERATING THOSE

620
00:23:38,560 --> 00:23:41,480
TFH CELLS, THESE VACCINES ARE

621
00:23:41,480 --> 00:23:44,280
GENERATING MEMORY TFH CELLS

622
00:23:44,280 --> 00:23:47,040
WHICH IS IMPORTANT FOR BOOSTER

623
00:23:47,040 --> 00:23:51,200
RESPONSES AND SUBSEQUENT TIME

624
00:23:51,200 --> 00:23:52,000
POINTS.

625
00:23:52,000 --> 00:23:53,360
FOR CD8 T-CELLS.

626
00:23:53,360 --> 00:23:54,880
THIS IS WHERE THE LITERATURE WAS

627
00:23:54,880 --> 00:23:59,360
A LOT MORE MIXED IN GOING BACK

628
00:23:59,360 --> 00:24:03,320
TO ACTUALLY EARLY PUBLICATIONS

629
00:24:03,320 --> 00:24:06,760
THAT WE'RE OBSERVING VERY

630
00:24:06,760 --> 00:24:09,800
SIMILAR IMMUNE RESPONSES BETWEEN

631
00:24:09,800 --> 00:24:13,480
THE PFIZER, AND MODERNA VACCINE

632
00:24:13,480 --> 00:24:15,600
EXCEPT IN CD8S WHERE PFIZER

633
00:24:15,600 --> 00:24:18,040
REPORTED RELATIVELY STRONG CD8

634
00:24:18,040 --> 00:24:20,440
RESPONSES AND CONTINUED WORKING

635
00:24:20,440 --> 00:24:23,200
WITH MODERNA GENERALLY REPORTED

636
00:24:23,200 --> 00:24:25,280
LOW TO UNDETECTABLE CD8 T-CELL

637
00:24:25,280 --> 00:24:25,520
RESPONSES.

638
00:24:25,520 --> 00:24:26,880
WE AND OTHER VS WORKED ON THIS

639
00:24:26,880 --> 00:24:30,280
IN A VARIETY OF WAYS, IN

640
00:24:30,280 --> 00:24:32,320
PARTICULAR IN THIS CONSORTIUM,

641
00:24:32,320 --> 00:24:34,760
IT WAS JOSE MATEUS, WORKING WITH

642
00:24:34,760 --> 00:24:35,160
[INDISCERNIBLE].

643
00:24:35,160 --> 00:24:39,120
AND SO A LOT OF THIS PARTICULAR

644
00:24:39,120 --> 00:24:41,040
PROJECT WAS ALEX SETTE, MYSELF

645
00:24:41,040 --> 00:24:47,200
AND DANIEL [INDISCERNIBLE] A

646
00:24:47,200 --> 00:24:50,240
REALLY FANTASTIC ASSISTANT

647
00:24:50,240 --> 00:24:53,120
RESEARCH PROFESSOR HERE, AND

648
00:24:53,120 --> 00:24:54,520
MATEUS HANDLING THE BRUNT OF THE

649
00:24:54,520 --> 00:24:57,160
WORK, WHERE WHAT WE SEE WITH

650
00:24:57,160 --> 00:24:59,280
ESSENTIALLY AN OVERNIGHT

651
00:24:59,280 --> 00:25:00,040
EPITHELIAL RACELLULAR CYTOKINE

652
00:25:00,040 --> 00:25:01,960
STAINING AND THE FOLLOWING THAT

653
00:25:01,960 --> 00:25:03,680
ACTUALLY MODERNA AND PFIZER

654
00:25:03,680 --> 00:25:06,320
VACCINES ARE QUITE GOOD AT

655
00:25:06,320 --> 00:25:07,360
ILLICITTING CD8 T-CELL RESPONSES

656
00:25:07,360 --> 00:25:10,280
TO THE EXTENT THEY ARE

657
00:25:10,280 --> 00:25:11,680
DETECTABLE IN 85-90% OF

658
00:25:11,680 --> 00:25:12,960
INDIVIDUALS AFTER IMMUNIZATION

659
00:25:12,960 --> 00:25:16,400
AND ARE STILL DETECTABLE AND

660
00:25:16,400 --> 00:25:17,640
2/3RDS OF INDIVIDUAL ADDED 6

661
00:25:17,640 --> 00:25:20,080
MONTHS NOT AS GREAT AS I WOULD

662
00:25:20,080 --> 00:25:22,160
LIKE BUT CERTAINLY PRESENT IN

663
00:25:22,160 --> 00:25:23,800
THE MAJORITY OF INDIVIDUALS AND

664
00:25:23,800 --> 00:25:30,120
IN FACT, THOSE RESPONSES ARE

665
00:25:30,120 --> 00:25:34,040
HIGHER OR AS HIGH THAN THE
J&  J

666
00:25:34,040 --> 00:25:34,920
VACCINE.

667
00:25:34,920 --> 00:25:37,360
WHAT OTHER GROUPS HAVE FOUND IS

668
00:25:37,360 --> 00:25:39,560
THAT IF INSTEAD YOU USE A

669
00:25:39,560 --> 00:25:45,080
SHORT-TERM STIMULATION ONLY A 6

670
00:25:45,080 --> 00:25:47,760
HOUR STIMULATION INSTEAD OF AN

671
00:25:47,760 --> 00:25:49,240
OVERNIGHT STIMULATION, WHAT YOU

672
00:25:49,240 --> 00:25:54,080
SEE IS RESPONSES TO AN ADEN O

673
00:25:54,080 --> 00:25:56,600
VACCINE IN HUMANS AND NOT TO THE

674
00:25:56,600 --> 00:25:58,480
RNA VACCINES SO THIS COMES IN

675
00:25:58,480 --> 00:26:01,720
DOWN GENERAL ASSAYS 1 USES, AND

676
00:26:01,720 --> 00:26:03,040
IN ASSESSING T-CELLS, ICS IS

677
00:26:03,040 --> 00:26:06,120
REALLY MORE IN LINE WITH WHAT

678
00:26:06,120 --> 00:26:06,840
YOU'RE INTERESTED IN BECAUSE DO

679
00:26:06,840 --> 00:26:09,160
YOU WANT TO KNOW ARE THE CELL

680
00:26:09,160 --> 00:26:11,720
SAYS THERE GOOD, THEY DID SEE A

681
00:26:11,720 --> 00:26:13,320
REINFECTION WOULD THEY RECALL,

682
00:26:13,320 --> 00:26:15,000
WHEREAS A 6 HOUR ASSAY IS

683
00:26:15,000 --> 00:26:17,960
TELLING YOU THE CAPACITY FOR

684
00:26:17,960 --> 00:26:21,680
IMMEDIATE EFFECTOR FUMPLEGZS

685
00:26:21,680 --> 00:26:25,800
WHICH IS VERY HIGH, WHETHER CD8

686
00:26:25,800 --> 00:26:27,000
T-CELL RESPONSE WAS ILLICITTED

687
00:26:27,000 --> 00:26:28,320
OR NOT.

688
00:26:28,320 --> 00:26:30,280
WE DO SEE A LITTLE INDICATION OF

689
00:26:30,280 --> 00:26:34,080
THE CD8 RESPONSE AFTER THE IN,

690
00:26:34,080 --> 00:26:35,920
OVAVAX, WE HAVE REPRODUCED THIS

691
00:26:35,920 --> 00:26:39,440
IN A COHORT, 25 INDIVIDUALS HAVE

692
00:26:39,440 --> 00:26:41,480
SOME DETECTABLE RESPONSE, I WILL

693
00:26:41,480 --> 00:26:44,160
NOT FOCUS ON THAT NOW BAH WE DO

694
00:26:44,160 --> 00:26:45,800
THINK THAT'S INTERESTING BECAUSE

695
00:26:45,800 --> 00:26:47,840
IT'S UNCONVENTIONAL FOR A

696
00:26:47,840 --> 00:26:48,800
PROTEIN VACCINE.

697
00:26:48,800 --> 00:26:50,480
AND THE FINAL IMMUNE MEMORY

698
00:26:50,480 --> 00:26:52,320
COMPONENT WE LOOKED AT ACROSS

699
00:26:52,320 --> 00:27:00,400
THESE 4 VACCINES HEAD-TO-HEAD

700
00:27:00,400 --> 00:27:02,760
WERE THE MEMORY B-CELLS WHICH

701
00:27:02,760 --> 00:27:06,640
WERE SPIKE AND RBD, WE FOUND ALL

702
00:27:06,640 --> 00:27:09,000
4 DO ILLICIT MEMORY B-CELLS AND

703
00:27:09,000 --> 00:27:11,400
THOSE DO INCREASE BETWEEN 3

704
00:27:11,400 --> 00:27:12,240
MONTHS AND 6 MONTHS POST

705
00:27:12,240 --> 00:27:13,640
VACCINATION AND I WILL COME BACK

706
00:27:13,640 --> 00:27:15,880
TO THIS AND IT IS INTERESTING

707
00:27:15,880 --> 00:27:18,240
THAT THESE GO UP, WHEREAS THE

708
00:27:18,240 --> 00:27:21,520
ANTIBODY TITERS ARE CLEARLY

709
00:27:21,520 --> 00:27:23,640
GOING DOWN AND THE T-CELL

710
00:27:23,640 --> 00:27:24,560
RESPONSES CERTAINLY AREN'T GOING

711
00:27:24,560 --> 00:27:26,560
UP AND THIS IS SIMILAR TO WHAT

712
00:27:26,560 --> 00:27:28,920
WE SEE IN THE CONTEXT OF

713
00:27:28,920 --> 00:27:31,960
INFECTION AND COMPARING ACROSS

714
00:27:31,960 --> 00:27:33,400
THE 4 VACCINES OTHERS AGAIN

715
00:27:33,400 --> 00:27:38,440
THEY'RE DOING A FANTASTIC JOB OF

716
00:27:38,440 --> 00:27:39,600
GENERATING B-CELL MEMORY, IT

717
00:27:39,600 --> 00:27:43,960
WILL BE ADEN O VIRAL VECTOR OR

718
00:27:43,960 --> 00:27:47,520
EVEN THE PROTEIN VACCINE.

719
00:27:47,520 --> 00:27:49,880
AND HOW DOES ALL THIS CONNECT TO

720
00:27:49,880 --> 00:27:52,960
PROTECT EVALUATION PROCESS

721
00:27:52,960 --> 00:27:53,320
IMMUNITY?

722
00:27:53,320 --> 00:27:56,640
AND I'LL COMMENT JUST A BIT ON

723
00:27:56,640 --> 00:28:03,040
THIS, HAVING TRAINED AS A

724
00:28:03,040 --> 00:28:04,120
VIROLOGIST IT'S ALWAYS CRITICAL

725
00:28:04,120 --> 00:28:05,960
TO THINK OF PROTECTIVE IMMUNITY

726
00:28:05,960 --> 00:28:08,600
IN THE CONTEXT OF THE ANATOMY

727
00:28:08,600 --> 00:28:10,080
AND PATHOGENESIS OF THE

728
00:28:10,080 --> 00:28:11,720
PARTICULAR VIRAL INFECTION THAT

729
00:28:11,720 --> 00:28:16,640
YOU ARE TRYING TO DEAL WITH AND

730
00:28:16,640 --> 00:28:20,600
IN THE CASE OF SARS COV-2 THIS

731
00:28:20,600 --> 00:28:23,880
IS CLEARLY A VIRUS THAT IS RAPID

732
00:28:23,880 --> 00:28:25,960
AT REPLICATING NAISAL CAVITIES

733
00:28:25,960 --> 00:28:32,280
AND ORAL CAVITIES AND VERY RAPID

734
00:28:32,280 --> 00:28:33,200
AT CAUSING ASYMPTOMATIC TO COLD

735
00:28:33,200 --> 00:28:36,400
LIKE DISEASE AND IT'S A RATHER

736
00:28:36,400 --> 00:28:45,520
DIFFICULT VIRUS TO STOP QUICKLY

737
00:28:45,520 --> 00:28:48,640
BUT IN TERMS OF PATHOGENESIS

738
00:28:48,640 --> 00:28:49,600
IT'S A RELATIVELY SLOW INFECTION

739
00:28:49,600 --> 00:28:52,360
IN THE LUNG AND INFECTION IN THE

740
00:28:52,360 --> 00:28:55,280
LUNG IS LOW WITH

741
00:28:55,280 --> 00:28:57,920
HOSPITALIZATIONS, FREQUENTLY 2

742
00:28:57,920 --> 00:29:01,680
WEEKS POST INFECTION OR SYMPTOM

743
00:29:01,680 --> 00:29:03,040
ONSET AND THIS PROTECTIVE

744
00:29:03,040 --> 00:29:05,200
IMMUNITY NEEDS TO KEEP THESE

745
00:29:05,200 --> 00:29:07,360
DIFFERENTIAL CONCEPTS OF

746
00:29:07,360 --> 00:29:09,000
PROTECTION, I. E. PROTECTION

747
00:29:09,000 --> 00:29:10,360
FROM INFECTION, VERSUS

748
00:29:10,360 --> 00:29:11,000
PROTECTION FROM SEVERE DISEASE

749
00:29:11,000 --> 00:29:12,360
IN MIND AS WELL AS THE DIFFERENT

750
00:29:12,360 --> 00:29:18,560
TISSUES IN WHICH THOSE ARE

751
00:29:18,560 --> 00:29:18,960
HAPPENING.

752
00:29:18,960 --> 00:29:20,240
IN BRIEF MY PERSONAL

753
00:29:20,240 --> 00:29:24,640
INTERPRETATION OF THE LITERATURE

754
00:29:24,640 --> 00:29:25,600
IS AS FOLLOWS.

755
00:29:25,600 --> 00:29:27,880
FIRST OF ALL THE SIMPLEST OPTION

756
00:29:27,880 --> 00:29:33,680
FOR ANY VACCINE IS HIGH LASTING

757
00:29:33,680 --> 00:29:39,760
NEUTRALIZING ASPECT BODIES, AND

758
00:29:39,760 --> 00:29:41,040
SARS-COV-2 IS PRIMARY FOR THIS,

759
00:29:41,040 --> 00:29:43,160
I MEAN THIS IS--THIS GENERAL

760
00:29:43,160 --> 00:29:44,560
TOPIC IS LITERALLY WHAT I

761
00:29:44,560 --> 00:29:47,920
FOUNDED MY LAB BASED ON 19 YEARS

762
00:29:47,920 --> 00:29:50,360
AGO WAS GENERATING NEUTRALIZING

763
00:29:50,360 --> 00:29:52,200
ANTIBODY RESPONSES IS KEY FOR

764
00:29:52,200 --> 00:29:54,040
MOST VACCINES AND WHAT WE NEEDED

765
00:29:54,040 --> 00:29:57,240
TO BETTER UNDERSTAND IS THE

766
00:29:57,240 --> 00:29:57,800
FUNDAMENTAL IMMUNOLOGICAL

767
00:29:57,800 --> 00:29:58,880
PRINCIPLES UNDERLYING HOW DO YOU

768
00:29:58,880 --> 00:29:59,720
GENERATE THOSE RESPONSES AND HOW

769
00:29:59,720 --> 00:30:01,720
DO YOU GET THEM TO BE DURABLE.

770
00:30:01,720 --> 00:30:05,920
BUT GIVEN THAT IT WAS CLEAR THAT

771
00:30:05,920 --> 00:30:09,040
INFECTION ITSELF DIDN'T ELICIT

772
00:30:09,040 --> 00:30:09,680
PARTICULARLY HIGH NEUTRALIZING

773
00:30:09,680 --> 00:30:12,280
ANTIBODIES AND THERE WAS LOTS OF

774
00:30:12,280 --> 00:30:13,720
CONCERN ABOUT DURABLE

775
00:30:13,720 --> 00:30:14,760
ANTIBODIES, WE AND OTHERS RAISE

776
00:30:14,760 --> 00:30:16,280
THE ISSUE OF LIF YOU CAN'T

777
00:30:16,280 --> 00:30:18,520
GENERATE HIGH ENOUGH LEVELS OF

778
00:30:18,520 --> 00:30:19,360
NEUTRALIZING ANTIBODIES OR IF

779
00:30:19,360 --> 00:30:22,360
THEY'RE NOT LONG LASTING, ARE

780
00:30:22,360 --> 00:30:24,280
THERE OTHER POTENTIAL MECHANISMS

781
00:30:24,280 --> 00:30:31,000
OF PROTECTIVE IMMUNITY AGAINST

782
00:30:31,000 --> 00:30:37,600
COVID-19 AND ADDITIONAL LAYERS

783
00:30:37,600 --> 00:30:37,960
OF ANTIBODIES.

784
00:30:37,960 --> 00:30:41,320
AND IT HAS BEEN HARD TO MAINTAIN

785
00:30:41,320 --> 00:30:42,320
ANTIBODIES LONG LASTING EITHER

786
00:30:42,320 --> 00:30:44,040
IN THE CONTEXT OF VACCINE BEING

787
00:30:44,040 --> 00:30:46,120
USED OR IN THE CONTEXT OF

788
00:30:46,120 --> 00:30:47,760
VARIANTS AND THE VITRATTURE HAS

789
00:30:47,760 --> 00:30:48,680
VARIOUS LINES OF EVIDENCE

790
00:30:48,680 --> 00:30:50,920
POINTING TO CONTRIBUTION OF

791
00:30:50,920 --> 00:30:52,400
T-CELLS AGAINST COVID-19.

792
00:30:52,400 --> 00:30:54,200
I WON'T GO THROUGH ALL OF THOSE

793
00:30:54,200 --> 00:30:56,080
IN THE INTEREST OF TIME WE CAN

794
00:30:56,080 --> 00:31:02,080
TALK ABOUT THEM IN THE Q&A.

795
00:31:02,080 --> 00:31:03,160
OVER ALL MY PERSPECTIVE OVERALL

796
00:31:03,160 --> 00:31:04,680
WHICH IS THE SAME BACK IN 2020

797
00:31:04,680 --> 00:31:06,760
IS THAT IT'S REASONABLE TO

798
00:31:06,760 --> 00:31:07,720
CONSIDER THAT HOSPITALIZATION

799
00:31:07,720 --> 00:31:09,680
LEVEL COVID-19 IS PREVENTED BY

800
00:31:09,680 --> 00:31:13,320
ANY DESCENT COMBINATION OF

801
00:31:13,320 --> 00:31:17,520
ANTIBODIES, MEMORY B-CELLS, CD4S

802
00:31:17,520 --> 00:31:17,760
AND CD8S.

803
00:31:17,760 --> 00:31:19,120
I HAVE FOUND THAT SOMETIMES

804
00:31:19,120 --> 00:31:20,560
PEOPLE HEAR THIS IN RATHER

805
00:31:20,560 --> 00:31:24,000
DIFFERENT WAYS SO I WILL SAY IT

806
00:31:24,000 --> 00:31:25,320
AGAIN A LITTLE BIT DIFFERENTLY,

807
00:31:25,320 --> 00:31:29,120
I AM NOT SAYING THAT T-CELLS,

808
00:31:29,120 --> 00:31:32,320
THAT ALL THE PROTECTIVE IMMUNITY

809
00:31:32,320 --> 00:31:34,320
AGAINST COVID-19 IS T-CELLS, SO

810
00:31:34,320 --> 00:31:35,360
T-CELLS IS THE MAJORITY OF IT,

811
00:31:35,360 --> 00:31:37,280
WHAT I AM SAYING IS THAT THE

812
00:31:37,280 --> 00:31:39,880
AVAILABILITY DATA POINT TO

813
00:31:39,880 --> 00:31:43,520
CONTRIBUTIONS OF T-CELLS AGAINST

814
00:31:43,520 --> 00:31:44,440
COVID-19 AND IN PARTICULARLY IN

815
00:31:44,440 --> 00:31:46,640
THE CONTEXT OF MORE SEVERE

816
00:31:46,640 --> 00:31:47,560
DISEASE, IT'S REASONABLE TO

817
00:31:47,560 --> 00:31:48,880
CONSIDER THAT THEY DO CONTRIBUTE

818
00:31:48,880 --> 00:31:55,680
AS WELL AS MEMORY B-CELLS

819
00:31:55,680 --> 00:31:56,000
CONTRIBUTING.

820
00:31:56,000 --> 00:31:59,760
AND I LIKE TO THINK OF THIS IN A

821
00:31:59,760 --> 00:32:01,840
LAYERED DEFENSES TYPE OF MODEL

822
00:32:01,840 --> 00:32:05,200
WHERE YOU WOULD LOVE TO HAVE THE

823
00:32:05,200 --> 00:32:06,640
VIRUS STOPPED BY NEUTRALIZING

824
00:32:06,640 --> 00:32:07,520
ANTIBODIES BUT IF YOU DON'T HAVE

825
00:32:07,520 --> 00:32:08,840
ENOUGH, DO YOU HAVE ADDITIONAL

826
00:32:08,840 --> 00:32:10,560
LAYERS OF THE DEFENSE THAT CAN

827
00:32:10,560 --> 00:32:13,080
HELP PREVENT SEVERE COVID-19

828
00:32:13,080 --> 00:32:13,520
FROM OCCURRING.

829
00:32:13,520 --> 00:32:16,040
AND REALLY IF YOU CAN CONSIDER

830
00:32:16,040 --> 00:32:17,280
LAYERED DEFENSES, WE NEED TO

831
00:32:17,280 --> 00:32:21,960
MOVE BEYOND JUST THINKING ABOUT

832
00:32:21,960 --> 00:32:22,760
CIRCULATING IMMUNITY WHICH IS

833
00:32:22,760 --> 00:32:24,040
EVERYTHING THAT I'VE TALKED

834
00:32:24,040 --> 00:32:26,240
ABOUT SO FAR, RIGHT, WERE ALL

835
00:32:26,240 --> 00:32:28,600
MEASUREMENTS IN THE BLOOD TO

836
00:32:28,600 --> 00:32:30,960
ALSO CONSIDERING LOCAL IMMUNITY,

837
00:32:30,960 --> 00:32:32,360
TISSUE RESIDENT MEMORY WHICH

838
00:32:32,360 --> 00:32:34,200
WOULD BE MORE FRONT LINE

839
00:32:34,200 --> 00:32:35,960
DEFENSES AND SO THERE HAVE BEEN

840
00:32:35,960 --> 00:32:38,360
PLENTY OF QUESTIONS ABOUT, WELL,

841
00:32:38,360 --> 00:32:39,800
DID INFECTION ILLICIT TISSUE

842
00:32:39,800 --> 00:32:42,000
RESIDENT MEMORY OR DO THE

843
00:32:42,000 --> 00:32:44,400
VACCINES ILLICIT TISSUE RESIDENT

844
00:32:44,400 --> 00:32:45,680
MEMORY, THOSE ARE MUCH HARDER

845
00:32:45,680 --> 00:32:47,440
QUESTIONS TO ASK BECAUSE YOU

846
00:32:47,440 --> 00:32:50,520
HAVE TO ACCESS HUMAN TISSUE TO

847
00:32:50,520 --> 00:32:50,720
DO SO.

848
00:32:50,720 --> 00:32:57,160
AND SO THOSE ANSWERS HAVE

849
00:32:57,160 --> 00:32:59,240
FOLLOWED BEHIND THE MUCH MORE

850
00:32:59,240 --> 00:33:05,280
COMMON MEASUREMENTS IN THE

851
00:33:05,280 --> 00:33:05,640
CIRCULATION.

852
00:33:05,640 --> 00:33:07,280
AND 1 OF THE FIRST STUDIES TO

853
00:33:07,280 --> 00:33:09,920
SHOW OR TO ASSESS WHETHER OR NOT

854
00:33:09,920 --> 00:33:16,960
THERE WAS TISSUE RESIDENT MEMORY

855
00:33:16,960 --> 00:33:18,080
AFTER SARS-COV-2 INFECTION WHICH

856
00:33:18,080 --> 00:33:25,280
IS THIS 1 LED BY THE WONDERFUL

857
00:33:25,280 --> 00:33:27,280
DONNA FAR BERNEA DEET AND MOST

858
00:33:27,280 --> 00:33:33,240
OF YOU WILL KNOW DONNA FAR

859
00:33:33,240 --> 00:33:33,960
 FARBER

860
00:33:33,960 --> 00:33:36,160
HAS DONE AMAZING WORK MAKING USE

861
00:33:36,160 --> 00:33:37,960
OF ORGAN DONOR PROGRAMS IN THE

862
00:33:37,960 --> 00:33:39,240
NEW YORK METROPOLITAN AREA TO

863
00:33:39,240 --> 00:33:42,680
DIRECTLY LOOK AT HUMAN IMMUNE

864
00:33:42,680 --> 00:33:44,440
MEMORY IN TISSUES, IN COMPARISON

865
00:33:44,440 --> 00:33:44,880
TO BLOOD.

866
00:33:44,880 --> 00:33:48,040
AND SO IN THIS PARTICULAR STUDY

867
00:33:48,040 --> 00:33:51,680
WHAT BECAME AVAILABLE JUST

868
00:33:51,680 --> 00:33:53,800
THROUGH THAT--JUST AN EXTENT

869
00:33:53,800 --> 00:33:55,000
RANDOM ENROLLMENT PROCESS WAS

870
00:33:55,000 --> 00:34:01,880
THERE WERE 4 INDIVIDUALS QUHO

871
00:34:01,880 --> 00:34:04,120
DIED FROM COVID UNRELATED CAUSES

872
00:34:04,120 --> 00:34:05,920
AND HAD UNREMARK CALVERT CASINGS

873
00:34:05,920 --> 00:34:07,800
OF COVID-19 AT SOME PREVIOUS

874
00:34:07,800 --> 00:34:10,920
TIME POINTS AND WE COMPARED

875
00:34:10,920 --> 00:34:12,040
WHETHER THOSE INDIVIDUALS, THOSE

876
00:34:12,040 --> 00:34:16,160
4 INDIVIDUALS WHO HAD A HISTORY

877
00:34:16,160 --> 00:34:18,560
OF COVID-19 DID THEY HAVE

878
00:34:18,560 --> 00:34:20,520
DETEBTIBLE B-CELL OR T-CELL

879
00:34:20,520 --> 00:34:23,360
MEMORY IN THEIR LUNGS AND THE

880
00:34:23,360 --> 00:34:24,240
LUNG DRAINING LYMPHNODES.

881
00:34:24,240 --> 00:34:26,240
SO THOSE INDIVIDUALS ARE SHOWN

882
00:34:26,240 --> 00:34:27,040
IN RED HERE.

883
00:34:27,040 --> 00:34:28,880
AND THE SHORT ANSWERS WERE YES,

884
00:34:28,880 --> 00:34:32,000
THEY HAD TISSUE RESIDENT MEMORY

885
00:34:32,000 --> 00:34:34,200
CD4 T-CELLS AND TISSUE MEMORY

886
00:34:34,200 --> 00:34:35,520
CD8 T-CELLS IN LUNGS AND IF

887
00:34:35,520 --> 00:34:38,920
ANYTHING, THERE WERE A HIGHER

888
00:34:38,920 --> 00:34:40,640
FREQUENCY OF VIRUS SPECIFIC CD8

889
00:34:40,640 --> 00:34:42,760
IN THE LUNGS THAN IN THE BLOOD,

890
00:34:42,760 --> 00:34:44,320
AND IT IS NOTABLE HERE BECAUSE

891
00:34:44,320 --> 00:34:46,360
AGAIN, THESE ARE PEOPLE WITH

892
00:34:46,360 --> 00:34:48,400
UNREMARKABLE CASES OF COVID-19

893
00:34:48,400 --> 00:34:50,000
AND THERE STILL WAS ENOUGH

894
00:34:50,000 --> 00:34:54,520
ANTIGEN IN THE LUNGS RIGHT TO

895
00:34:54,520 --> 00:34:58,360
RESULT IN SIGNIFICANT AMOUNTS OF

896
00:34:58,360 --> 00:34:59,440
RESIDENT MEMORY T-CELLS.

897
00:34:59,440 --> 00:35:01,240
WHAT ALEX IN MY GROUP WAS

898
00:35:01,240 --> 00:35:03,440
RESPONSIBLE FOR WAS ASKING THE

899
00:35:03,440 --> 00:35:05,280
QUESTION WERE THERE RESIDENT

900
00:35:05,280 --> 00:35:10,280
MEMORY B-CELLS WHICH IS A MUCH

901
00:35:10,280 --> 00:35:11,240
LESS STUDIED AREA, PARTICULARLY

902
00:35:11,240 --> 00:35:13,920
IN HUMANS SO WE WERE THE FIRST

903
00:35:13,920 --> 00:35:17,360
TO DEMONSTRATE THAT THERE ARE

904
00:35:17,360 --> 00:35:18,960
INDEED ROBUST AMOUNTS OF

905
00:35:18,960 --> 00:35:20,240
RESIDENT MEMORY B-CELLS IN THE

906
00:35:20,240 --> 00:35:22,800
LUNG, SPIKE SPECIFIC AND RBD

907
00:35:22,800 --> 00:35:23,800
SPECIFIC RESIDENT MEMORY B-CELLS

908
00:35:23,800 --> 00:35:27,240
IN THE LUNGS OF PEOPLE WHO HAVE

909
00:35:27,240 --> 00:35:31,560
HAD AGAIN UNREMARKABLE CASES OF

910
00:35:31,560 --> 00:35:33,720
COVID-19 COMPARED TO NEGATIVE

911
00:35:33,720 --> 00:35:34,000
CONTROLS.

912
00:35:34,000 --> 00:35:35,960
THESE PEOPLE WERE ALL ENROLLED

913
00:35:35,960 --> 00:35:36,680
BEFORE THE VACCINES WERE

914
00:35:36,680 --> 00:35:39,080
AVAILABLE SO WE KNOW THESE ARE

915
00:35:39,080 --> 00:35:41,360
ALL INFECTION INDUCED EVENTS,

916
00:35:41,360 --> 00:35:41,720
OKAY.

917
00:35:41,720 --> 00:35:43,720
AND WE DID ALSO SEE MEMORY IN

918
00:35:43,720 --> 00:35:48,320
THE LUNG DRAINING LYMPHNODES,

919
00:35:48,320 --> 00:35:49,920
THAT'S WHAT LLN STANDS FOR AS

920
00:35:49,920 --> 00:35:51,520
WELL AS GUT TRAINING LYMPHNODES

921
00:35:51,520 --> 00:35:54,800
WHICH IS AN IMPORTANT AND

922
00:35:54,800 --> 00:35:56,200
INTERESTING TOPIC.

923
00:35:56,200 --> 00:36:01,120
OTHER LABS HAVE ALSO PUBLISHED

924
00:36:01,120 --> 00:36:02,880
THAT MEMORY T-CELLS ARE

925
00:36:02,880 --> 00:36:05,240
DETECTABLE IN LUNGS OF INVESTED

926
00:36:05,240 --> 00:36:06,600
INDIVIDUALS AND MORE RECENTLY

927
00:36:06,600 --> 00:36:10,360
THERE'S BEEN NICE DATA AVAILABLE

928
00:36:10,360 --> 00:36:18,240
ON NAISAL, NAISAL PHARYNGIAL

929
00:36:18,240 --> 00:36:21,000
MEMORY CELLS, BY UPON J. SUN AND

930
00:36:21,000 --> 00:36:22,280
[INDISCERNIBLE] AMONG RPGHTS

931
00:36:22,280 --> 00:36:23,560
DEMONSTRATING THERE CLEARLY ARE

932
00:36:23,560 --> 00:36:25,600
CDEFICIENCY, 8 AND CD4 MEMORY

933
00:36:25,600 --> 00:36:29,680
T-CELLS IN THESE TISSUES AFTER

934
00:36:29,680 --> 00:36:32,800
INFECTION AND NOT AFTER

935
00:36:32,800 --> 00:36:34,200
VACCINATION WITH R NA VACCINES

936
00:36:34,200 --> 00:36:38,840
WHICH I THINK LARGELY MATCHES

937
00:36:38,840 --> 00:36:39,840
OUR EXPECTATION BUT IS IMPORTANT

938
00:36:39,840 --> 00:36:41,880
TO SEE AND ANYTHINGLY IT LOOKS

939
00:36:41,880 --> 00:36:44,880
LIKE THESE MAY BE RELATIVELY

940
00:36:44,880 --> 00:36:46,080
DURABLE RESPONSES WHICH WARRANTS

941
00:36:46,080 --> 00:36:47,440
MORE INFORMATION BUT AT LEAST

942
00:36:47,440 --> 00:36:48,600
FOR THE MOMENT IT DOESN'T LOOK

943
00:36:48,600 --> 00:36:59,080
LIKE THEY JUST SHOW UP FOR 2

944
00:37:00,560 --> 00:37:02,160
MONTHS AND IN THIS PERSON WHO IS

945
00:37:02,160 --> 00:37:04,600
INFECTED OR IN HYBRID IMMUNITY

946
00:37:04,600 --> 00:37:06,800
IF YOU'VE BEEN INFEBTED OR

947
00:37:06,800 --> 00:37:08,040
VACCINATED AND THEN VACCINATED

948
00:37:08,040 --> 00:37:09,560
AND HAVE A BREAK THROUGH

949
00:37:09,560 --> 00:37:11,000
INFECTION, YOU END UP WITH

950
00:37:11,000 --> 00:37:12,480
HYBRID IMMUNITY WHERE YOU GET

951
00:37:12,480 --> 00:37:14,880
TISSUE RESIDENT MEMORY CELLS,

952
00:37:14,880 --> 00:37:16,560
REALLY AS VERY STRONG

953
00:37:16,560 --> 00:37:24,760
CIRCULATING MEMORY GENERATED BY

954
00:37:24,760 --> 00:37:25,080
VACCINATION.

955
00:37:25,080 --> 00:37:33,840
THERE WAS 1 ADDITIONAL PIECE OF

956
00:37:33,840 --> 00:37:37,160
INFORMATION BY THESE ORGAN DO

957
00:37:37,160 --> 00:37:38,200
DONORS THAT SURPRISED US AND

958
00:37:38,200 --> 00:37:40,360
THAT WAS WHEN WE LOOKED IN THE

959
00:37:40,360 --> 00:37:41,640
LUNG DRAINING LYMPHNODES WE

960
00:37:41,640 --> 00:37:43,040
COULD SEE GERMINAL CENTERS THAT

961
00:37:43,040 --> 00:37:44,760
IN AND OF ITSELF IS

962
00:37:44,760 --> 00:37:46,040
UNSURPRISING, PEOPLE DO GET

963
00:37:46,040 --> 00:37:47,120
OBVIOUSLY EXPOSED TO MANY

964
00:37:47,120 --> 00:37:51,280
THINGS, BUT WE HAD THE CAPACITY

965
00:37:51,280 --> 00:37:53,080
WITH FLUORESCENT PROBE STAINING

966
00:37:53,080 --> 00:37:56,000
TO DEMONSTRATE THERE WERE

967
00:37:56,000 --> 00:37:57,880
SARS-COV-2 SPIKE SPECIFIC

968
00:37:57,880 --> 00:37:59,520
GERMINAL CENTER B-CELLS IN THESE

969
00:37:59,520 --> 00:38:01,680
LUNG DRAINING LYMPHNODES AND THE

970
00:38:01,680 --> 00:38:05,640
PREVIOUS PROBABLY FOR 3 OUT OF 4

971
00:38:05,640 --> 00:38:08,000
OF THESE INDIVIDUALS AND THEY'RE

972
00:38:08,000 --> 00:38:09,400
PREVIOUSLY RECORDED INFECTIONS

973
00:38:09,400 --> 00:38:13,840
WERE 6 MONTHS OR MORE IN THE

974
00:38:13,840 --> 00:38:16,080
PAST AND SO THIS SUGGESTS THAT

975
00:38:16,080 --> 00:38:17,280
THERE WERE ONGOING GERMINAL

976
00:38:17,280 --> 00:38:19,240
CENTERS FOR AT LEAST 6 MONTHS

977
00:38:19,240 --> 00:38:23,200
AFTER AGAIN AN UNREMARKABLE CASE

978
00:38:23,200 --> 00:38:27,960
OF COVID-19 IN THESE LUNG

979
00:38:27,960 --> 00:38:28,600
DRAINING LYMPHNODES.

980
00:38:28,600 --> 00:38:31,120
AND SO NOW, WITH THAT, I'LL

981
00:38:31,120 --> 00:38:34,400
PIVOT TO THESE CONNECTIONS

982
00:38:34,400 --> 00:38:35,160
BETWEEN WHAT WE'VE BEEN

983
00:38:35,160 --> 00:38:36,920
OBSERVING IN THE CONTEXT OF

984
00:38:36,920 --> 00:38:38,520
COVID-19 AND COVID-19 VACCINES

985
00:38:38,520 --> 00:38:41,720
AND WHAT WE'VE BEEN WORKING ON I

986
00:38:41,720 --> 00:38:45,280
WOULD SAY MORE BROADLY IN

987
00:38:45,280 --> 00:38:48,680
VACCINE IMMUNOLOGY, PARTICULARLY

988
00:38:48,680 --> 00:38:50,640
USING--WORKING ON HIV VACCINES

989
00:38:50,640 --> 00:38:52,240
BOTH BECAUSE THE WORLD NEEDS AN

990
00:38:52,240 --> 00:38:54,480
HIV VACCINE AND BECAUSE IT'S A

991
00:38:54,480 --> 00:38:56,240
RATHER FANTASTIC MODEL SYSTEM

992
00:38:56,240 --> 00:38:57,040
FOR VACCINE IMMUNOLOGY BECAUSE

993
00:38:57,040 --> 00:39:04,320
OF THE MANY TOOLS WE HAVE

994
00:39:04,320 --> 00:39:04,880
AVAILABLE.

995
00:39:04,880 --> 00:39:07,840
WE--I MENTIONED TF8 CELLS BEING

996
00:39:07,840 --> 00:39:10,760
IMPORTANT BEING ESSENTIAL FOR

997
00:39:10,760 --> 00:39:13,080
T-CELL AND B-CELLS, AND WE'VE

998
00:39:13,080 --> 00:39:14,400
BEEN STUDYING TFH CELLS FOR A

999
00:39:14,400 --> 00:39:18,280
NUMBER OF YEARS NOW AND AFTER WE

1000
00:39:18,280 --> 00:39:22,160
AND OTHERS HOPE TO ESTABLISH

1001
00:39:22,160 --> 00:39:24,240
THAT TF8 STYLES WERE REAL AND

1002
00:39:24,240 --> 00:39:26,120
IMPORTANT IN 2009, THERE HAVE

1003
00:39:26,120 --> 00:39:29,520
BEEN A LOT OF GREAT ADVANCES IN

1004
00:39:29,520 --> 00:39:32,400
THAT FIELD BY MANY GROUPS

1005
00:39:32,400 --> 00:39:33,280
INCLUDING PAM [INDISCERNIBLE]

1006
00:39:33,280 --> 00:39:36,040
GROUP AT NIH AND MANY OTHERS AND

1007
00:39:36,040 --> 00:39:38,880
BETWEEN THE ENTIRE WORK OF THE

1008
00:39:38,880 --> 00:39:46,440
FEELTD WE HAVE LEARNED MANY

1009
00:39:46,440 --> 00:39:48,400
THINGS ABOUT TFH CELLS, AND THEY

1010
00:39:48,400 --> 00:39:50,440
HELP THESE CELLS EARLY IN IMMUNE

1011
00:39:50,440 --> 00:39:52,840
RESPONSES AS EARLY AS THE FIRST

1012
00:39:52,840 --> 00:39:55,480
FEW DAYS, BUT ARE THEN

1013
00:39:55,480 --> 00:39:57,640
ABSOLUTELY CRITICAL IN GERMINAL

1014
00:39:57,640 --> 00:40:01,960
CENTERS FOR THE ENTIRE PROCESS

1015
00:40:01,960 --> 00:40:06,560
OF GERM LINE CENTERS INCLUDING

1016
00:40:06,560 --> 00:40:11,320
THE PRODUCTS, THE PRODUCTS

1017
00:40:11,320 --> 00:40:11,720
THEMSELVES.

1018
00:40:11,720 --> 00:40:14,000
GERMINAL CENTERS ARE ABSOLUTELY

1019
00:40:14,000 --> 00:40:17,960
AMAZING IMMUNOLOGICAL EVENTS AND

1020
00:40:17,960 --> 00:40:18,520
STRUCTURES.

1021
00:40:18,520 --> 00:40:23,000
THESE ARE LITERALLY REALTIME

1022
00:40:23,000 --> 00:40:24,240
EVOLUTION WHERE ANY EVOLUTIONARY

1023
00:40:24,240 --> 00:40:26,200
PROCESS HAS TO HAVE GENERATIONS

1024
00:40:26,200 --> 00:40:26,680
ISSUES RIGHT?

1025
00:40:26,680 --> 00:40:28,920
SO THAT'S CELL DIVISION,

1026
00:40:28,920 --> 00:40:31,280
MUTATIONS, WHICH ARE SOMATIC

1027
00:40:31,280 --> 00:40:32,360
HYPERMUTATIONS THAT OCCUR, IN

1028
00:40:32,360 --> 00:40:35,680
THE CENTERS AND A SELECTIVE

1029
00:40:35,680 --> 00:40:37,080
PRESSURE OR A LIMITING RESOURCE

1030
00:40:37,080 --> 00:40:39,680
AND IN THIS CASE, THE LIMITING

1031
00:40:39,680 --> 00:40:41,520
RESOURCE IS ACTUALLY GENERALLY

1032
00:40:41,520 --> 00:40:43,520
THE TFH CELLS AND THE TFH CELLS

1033
00:40:43,520 --> 00:40:45,880
ARE LIMITED IN NUMBER AND

1034
00:40:45,880 --> 00:40:47,000
PROVOID A LIMITED AMOUNT OF HELP

1035
00:40:47,000 --> 00:40:50,200
TO THE B-CELLS AND THEY SIGNAL

1036
00:40:50,200 --> 00:40:51,880
THE B-CELLS TO UNDERGO MUTATION

1037
00:40:51,880 --> 00:40:53,920
AND PROLIFERATION AND THEN

1038
00:40:53,920 --> 00:40:56,480
AMONGST THOSE EVENTS, AFTER A

1039
00:40:56,480 --> 00:40:57,600
PSYCHOEVENT, THOSE B-CELLS HAVE

1040
00:40:57,600 --> 00:40:59,640
TO COME BACK, INTERACT WITH THE

1041
00:40:59,640 --> 00:41:01,720
TFH CELLS AGAIN AND OVERALL IN

1042
00:41:01,720 --> 00:41:03,800
THE POP IELINGS, THERE'S A

1043
00:41:03,800 --> 00:41:05,440
TENDENCY FOR THE B-CELLS TO HAVE

1044
00:41:05,440 --> 00:41:06,360
THE HIGHEST AFFINITY TO GET THE

1045
00:41:06,360 --> 00:41:09,920
MOST HELP FROM THE TFH CELLS AND

1046
00:41:09,920 --> 00:41:11,280
THEIR ADDITIONAL SIGNALS, THAT

1047
00:41:11,280 --> 00:41:14,160
GO ON, BEYOND DRIVING THIS

1048
00:41:14,160 --> 00:41:16,480
EVOLUTIONARY PROCESS, CAN THEN

1049
00:41:16,480 --> 00:41:17,760
DRIVE FURTHER DIFFERENTIATION TO

1050
00:41:17,760 --> 00:41:19,400
GENERATE PLASMA CELLS OUT OF

1051
00:41:19,400 --> 00:41:25,400
THAT GERMINAL CENTER B-CELLS OR

1052
00:41:25,400 --> 00:41:25,960
MEMORY B-CELLS.

1053
00:41:25,960 --> 00:41:27,720
AND IT'S VERY CLEAR FROM

1054
00:41:27,720 --> 00:41:29,360
BEAUTIFUL WORK FROM A NUMBER OF

1055
00:41:29,360 --> 00:41:32,800
LABS THAT REALLY ESSENTIALLY,

1056
00:41:32,800 --> 00:41:36,280
ALL--AS I WAS SAYING EARLIER ALL

1057
00:41:36,280 --> 00:41:37,840
OF YOUR OMICRON NEUTRALIZING

1058
00:41:37,840 --> 00:41:39,360
ANTIBODIES IN THE BLOOD ARE

1059
00:41:39,360 --> 00:41:41,120
COMING FROM THIS PROCESS WHERE A

1060
00:41:41,120 --> 00:41:42,440
B-CELL THAT STARTED WITH THE

1061
00:41:42,440 --> 00:41:44,480
ABILITY TO RECOGNIZE THE

1062
00:41:44,480 --> 00:41:46,600
ANCESTRAL STRAIN PRESENT IN YOUR

1063
00:41:46,600 --> 00:41:48,240
ORIGINAL MODERNA OR PFIZER OR

1064
00:41:48,240 --> 00:41:51,440
OTHER VACCINE, THOSE B-CELLS

1065
00:41:51,440 --> 00:41:52,360
UNDERWENT EXTENSIVE MUTATION AND

1066
00:41:52,360 --> 00:41:54,200
SELECTION AND A NUMBER OF THEM

1067
00:41:54,200 --> 00:41:56,960
BECAME CAPABLE OF BINDING TO

1068
00:41:56,960 --> 00:41:58,360
OMICRON, WITH HIGH AFENNITY EVEN

1069
00:41:58,360 --> 00:42:01,160
THOUGH THEY'VE NEVER SEEN

1070
00:42:01,160 --> 00:42:02,160
OMICRON, AND MAKING ANTIBODIES

1071
00:42:02,160 --> 00:42:04,240
THAT COULD DO SO.

1072
00:42:04,240 --> 00:42:06,600
OR IN FACT, IN GENERAL, THAT

1073
00:42:06,600 --> 00:42:08,600
DIDN'T HAPPEN DIRECTLY AFTER THE

1074
00:42:08,600 --> 00:42:10,280
FIRST OR SECOND IMMUNIZATION,

1075
00:42:10,280 --> 00:42:12,200
WHAT WAS HAPPENING AFTER THE

1076
00:42:12,200 --> 00:42:13,440
FIRST AND SECOND IMMUNIZATION

1077
00:42:13,440 --> 00:42:15,080
FOR THE GENERATION OF MEMORY

1078
00:42:15,080 --> 00:42:18,080
B-CELLS THAT HAD THE POTENTIAL

1079
00:42:18,080 --> 00:42:20,440
TO BIND OMICRON AND REALLY 1 KEY

1080
00:42:20,440 --> 00:42:21,640
ASPECT OF GERMINAL CENTERS

1081
00:42:21,640 --> 00:42:23,440
THAT'S BECOMING MORE AND MORE

1082
00:42:23,440 --> 00:42:26,520
APPRECIATED IS THAT THEY REALLY

1083
00:42:26,520 --> 00:42:29,760
ARE A SOURCE OF GENERATING

1084
00:42:29,760 --> 00:42:31,760
B-CELL DIVERSITY FROM A TELEIO

1085
00:42:31,760 --> 00:42:34,400
LOGICAL PERSPECTIVE OF THE

1086
00:42:34,400 --> 00:42:36,240
IMMUNE SYSTEM RECOGNIZING THAT

1087
00:42:36,240 --> 00:42:37,880
THE PRESENCE OF 1 VIRUS SLOWING

1088
00:42:37,880 --> 00:42:40,000
UP NOW MAY MEAN THAT THEY WOULD

1089
00:42:40,000 --> 00:42:42,040
BE RELATED VIRUSES SHOWING UP IN

1090
00:42:42,040 --> 00:42:44,480
THE FUTURE AND THUS MAKING A

1091
00:42:44,480 --> 00:42:48,000
DIVERSITY OF MEMORY B-CELLS,

1092
00:42:48,000 --> 00:42:50,160
MIGHT BE QUITE HELPFUL IN

1093
00:42:50,160 --> 00:42:51,760
RECOGNIZING VIRAL VARIANTS IN

1094
00:42:51,760 --> 00:42:56,320
THE FUTURE AND INDEED THAT'S

1095
00:42:56,320 --> 00:42:57,520
EXACTLY WHAT GETS SEEN.

1096
00:42:57,520 --> 00:42:59,800
WE HAVE BEEN TRYING TO

1097
00:42:59,800 --> 00:43:01,440
UNDERSTAND THOSE GERMINAL CENTER

1098
00:43:01,440 --> 00:43:04,520
PROCESSES FROM OTHER

1099
00:43:04,520 --> 00:43:04,840
PERSPECTIVES.

1100
00:43:04,840 --> 00:43:06,560
THE SIMPLEST MODEL OF A GERMINAL

1101
00:43:06,560 --> 00:43:12,240
CENTER HAS ALWAYS BEEN THAT IT'S

1102
00:43:12,240 --> 00:43:13,760
WHERE YOU HAVE RAPID EVOLUTION

1103
00:43:13,760 --> 00:43:15,280
AND SELECTION OF THE BEST

1104
00:43:15,280 --> 00:43:20,440
B-CELLS AND THE BEST B-CELLS WIN

1105
00:43:20,440 --> 00:43:23,280
OUT AND WHAT WE SAID WAS THAT

1106
00:43:23,280 --> 00:43:25,680
DIDN'T REALLY MATCH OUR

1107
00:43:25,680 --> 00:43:28,200
OBSERVATIONS IN SOME OF THE HIV

1108
00:43:28,200 --> 00:43:29,840
VACCINE FIELDS WHERE IT'S BEEN

1109
00:43:29,840 --> 00:43:32,120
VERY DIFFICULT TO GENERATE

1110
00:43:32,120 --> 00:43:33,120
NEUTRALIZING ANTIBODIES, SO, WHY

1111
00:43:33,120 --> 00:43:36,720
WOULD YOU HAVE SITUATIONS WHERE

1112
00:43:36,720 --> 00:43:38,200
YOU WOULD IMMUNIZE WITH AN

1113
00:43:38,200 --> 00:43:40,440
ANTIGEN THAT HAD NEUTRALIZING

1114
00:43:40,440 --> 00:43:41,880
ANTIBODY EPITOPES ON IT BUT YOU

1115
00:43:41,880 --> 00:43:44,160
WOULDN'T SEE THOSE NEUTRALIZING

1116
00:43:44,160 --> 00:43:44,800
ANTIBODIES COME OUT.

1117
00:43:44,800 --> 00:43:47,200
AND WE CONSIDERED THAT IMMUNO

1118
00:43:47,200 --> 00:43:53,160
DOMINANCE MIGHT BE A  REASON FOR

1119
00:43:53,160 --> 00:43:53,480
THAT PROBLEM.

1120
00:43:53,480 --> 00:43:54,800
THAT WAS CERTAINLY IN THE HIV

1121
00:43:54,800 --> 00:43:56,280
FIELD THAT WAS CONTROVERSIAL AS

1122
00:43:56,280 --> 00:44:02,520
WELL AS SOME OTHER FIELDS AND SO

1123
00:44:02,520 --> 00:44:05,360
WE TRIED TO LAYOUT SOME CLEAR

1124
00:44:05,360 --> 00:44:06,920
CONCEPTS THAT WERE TESTABLE THAT

1125
00:44:06,920 --> 00:44:09,960
WOULD ADDRESS THOSE B-CELLS AND

1126
00:44:09,960 --> 00:44:12,120
IMMUNO DOMINANCE EXISTS AND IF

1127
00:44:12,120 --> 00:44:15,400
IT DID WHAT PARAMETERS DOES IT

1128
00:44:15,400 --> 00:44:18,160
ABIDE BY AND SO 1 MODEL WAS THAT

1129
00:44:18,160 --> 00:44:21,080
YOU CAN GET IMMUNO RESPONSES

1130
00:44:21,080 --> 00:44:21,920
BASED ON INFINITY DISPARITY, AND

1131
00:44:21,920 --> 00:44:24,520
IF YOU HAVE FOR EXAMPLE, EASY

1132
00:44:24,520 --> 00:44:28,720
EPITOPES ON AN ANTIGEN, LET'S

1133
00:44:28,720 --> 00:44:30,680
CALL THESE THE NONNEUTRALLIZING

1134
00:44:30,680 --> 00:44:32,520
EPITOPES, IF THESE HAVE A BETTER

1135
00:44:32,520 --> 00:44:35,120
AFFINITY THAN THE B-CELLS THAT

1136
00:44:35,120 --> 00:44:36,440
RECOGNIZE DIFFICULT NEUTRALIZING

1137
00:44:36,440 --> 00:44:37,800
EPITOPES THEN PERHAPS THE

1138
00:44:37,800 --> 00:44:40,840
B-CELLS THAT RECOGNIZE THE

1139
00:44:40,840 --> 00:44:41,880
NONNEUTRALLIZING EPITOPES, WIN

1140
00:44:41,880 --> 00:44:43,000
OUT IN COMPETITION SIMPLY BUZZ

1141
00:44:43,000 --> 00:44:46,760
THEY START WITH A BETTER

1142
00:44:46,760 --> 00:44:47,200
AFFINITY ON AVERAGE.

1143
00:44:47,200 --> 00:44:50,320
OR YOU COULD HAVE A NUMERICAL

1144
00:44:50,320 --> 00:44:51,360
DISPARITY WHERE MAYBE THERE ARE

1145
00:44:51,360 --> 00:44:55,440
JUST MANY MORE B-CELLS THAT CAN

1146
00:44:55,440 --> 00:44:56,560
RECOGNIZE NONNEUTRALLIZING

1147
00:44:56,560 --> 00:44:57,840
EPITELOMERES, THAN NEUTRALIZING

1148
00:44:57,840 --> 00:44:59,560
EPITOPES AND THAT NUMERICAL

1149
00:44:59,560 --> 00:45:00,760
DISPARITY MIGHT BE SO LARGE THAT

1150
00:45:00,760 --> 00:45:03,840
YOU FAILED TO GET NEUTRALIZING

1151
00:45:03,840 --> 00:45:07,000
ANTIBODY RESPONSES BECAUSE THEY

1152
00:45:07,000 --> 00:45:07,920
GET NIEWMERICALLY OUTCOMPETED.

1153
00:45:07,920 --> 00:45:09,880
THESE CAN HAPPEN THROUGH

1154
00:45:09,880 --> 00:45:12,880
MULTIPLE MECHANISMS, 1ICISMEM

1155
00:45:12,880 --> 00:45:14,960
CONCEPT IS GLYCANS SO VIRUSES

1156
00:45:14,960 --> 00:45:17,760
LIKE HIV, THIS IS THE ENVELOPE

1157
00:45:17,760 --> 00:45:20,360
SHOWN WITH GLYCANS SHOWN IN

1158
00:45:20,360 --> 00:45:23,400
BLUE, THESE ARE SELF-GLYCANS SO

1159
00:45:23,400 --> 00:45:25,400
HUMAN B-CELLS THAT DEVELOP IN

1160
00:45:25,400 --> 00:45:28,480
HUMAN B-CELLS THAT HAVE HIGH

1161
00:45:28,480 --> 00:45:31,640
AFFINITY FOR CELL GLYCANS GET

1162
00:45:31,640 --> 00:45:32,840
ELIMINATED BECAUSE THEY'RE

1163
00:45:32,840 --> 00:45:34,000
AUTOREACTIVE SO YOU

1164
00:45:34,000 --> 00:45:35,720
INTRINSICALLY HAVE LOWER

1165
00:45:35,720 --> 00:45:37,120
AFFINITY B-CELLS AND RARE

1166
00:45:37,120 --> 00:45:39,560
B-CELLS IF THE EPITOPES ARE

1167
00:45:39,560 --> 00:45:45,240
GOING TO INVOLVE A SELF-GLYCAN

1168
00:45:45,240 --> 00:45:45,520
COMPONENT.

1169
00:45:45,520 --> 00:45:47,440
ADDITIONALLY, IT COULD BE THAT

1170
00:45:47,440 --> 00:45:50,400
LIMITED T-CELL HELP COULD HELP

1171
00:45:50,400 --> 00:45:51,600
IN B-CELL IMMUNE DOMINANCE

1172
00:45:51,600 --> 00:45:53,360
BECAUSE AFTER AN INITIAL PRIMING

1173
00:45:53,360 --> 00:45:57,000
EVENT THERE ARE VERY FEW CD4

1174
00:45:57,000 --> 00:45:57,960
T-CELLS IN THE FIRST FEW DAYS

1175
00:45:57,960 --> 00:46:01,400
AND YET WE KNOW THAT MOST IMMUNE

1176
00:46:01,400 --> 00:46:02,640
RESPONSES B-CELLS REALLY ONLY

1177
00:46:02,640 --> 00:46:04,440
UNDER GO 1 CELL DIVISION BEFORE

1178
00:46:04,440 --> 00:46:07,200
THEY SEE T-CELL HELP AND THEN

1179
00:46:07,200 --> 00:46:08,960
ALL SUBSEQUENT CELL DIVISIONS

1180
00:46:08,960 --> 00:46:10,160
ARE T-CELL DEPENDENT IN A

1181
00:46:10,160 --> 00:46:12,600
MAJORITY OF CASES AND IN THAT

1182
00:46:12,600 --> 00:46:14,280
SCENARIO WITH A LIMITED NUMBER,

1183
00:46:14,280 --> 00:46:16,120
IT'S PRETTY EASY TO IMAGINE THAT

1184
00:46:16,120 --> 00:46:18,360
SOME B-CELLS MAYBE JUST THE MOST

1185
00:46:18,360 --> 00:46:19,440
COMMON B-CELLS WOULD GET HELP

1186
00:46:19,440 --> 00:46:21,280
AND MANY OTHERS WOULD NOT AND

1187
00:46:21,280 --> 00:46:24,480
THEN THESE CELLS WOULD START

1188
00:46:24,480 --> 00:46:25,120
EXPONENTIALLY DIVIDING, RIGHT

1189
00:46:25,120 --> 00:46:26,520
WHICH WHICH MAKES IT VERY

1190
00:46:26,520 --> 00:46:28,000
UNLIKELY THAT THESE WOULD EVER

1191
00:46:28,000 --> 00:46:30,520
BE ABLE TO CATCH UP.

1192
00:46:30,520 --> 00:46:35,400
SO WE PUT THESE OUT THERE AND WE

1193
00:46:35,400 --> 00:46:37,040
TESTED THESE IDEAS AND IN BRIEF

1194
00:46:37,040 --> 00:46:41,000
AND IN THE INTEREST OF TIME WE

1195
00:46:41,000 --> 00:46:43,400
FIRST SHOWED THAT IN HUMAN NAIVE

1196
00:46:43,400 --> 00:46:44,920
B-CELLS, THIS DEFINITELY OCCURS,

1197
00:46:44,920 --> 00:46:46,680
YOU CAN HAVE SIGNIFICANT

1198
00:46:46,680 --> 00:46:48,800
DIFFERENCES IN AFFINITY BETWEEN

1199
00:46:48,800 --> 00:46:50,120
NAIVE B-CELLS, AND 2 DIFFERENT

1200
00:46:50,120 --> 00:46:51,960
EPITOPE TAUPES AND YOU CAN HAVE

1201
00:46:51,960 --> 00:46:53,560
LARGE DIFFERENCES IN

1202
00:46:53,560 --> 00:46:57,360
FREQUENCIES, SO FOR A BROADLY

1203
00:46:57,360 --> 00:46:58,880
NEUTRALIZING EPITOPE, THE VRC 1

1204
00:46:58,880 --> 00:47:01,200
CLASS WHICH IS THE VRC IS VERY,

1205
00:47:01,200 --> 00:47:02,520
VERY FAMILIAR WITH, WE FOUND

1206
00:47:02,520 --> 00:47:05,480
THOSE ARE FREQUENT AT HIGH

1207
00:47:05,480 --> 00:47:08,120
AFFINITY AT 1 AND A MILLION TO

1208
00:47:08,120 --> 00:47:10,720
THE HUMAN B-CELLS WHERE IN AN

1209
00:47:10,720 --> 00:47:12,640
EASY EPITOPE THERE MIGHT BE 1

1210
00:47:12,640 --> 00:47:13,080
AND 5000.

1211
00:47:13,080 --> 00:47:18,560
THAT IS A REALEE BIG IN

1212
00:47:18,560 --> 00:47:20,040
FREQUENCIES FROM A COMPETITIVE

1213
00:47:20,040 --> 00:47:20,320
STANCE.

1214
00:47:20,320 --> 00:47:22,880
SO WE THEN TESTED THESE IN

1215
00:47:22,880 --> 00:47:26,080
DIFFERENT MOUSE MODELS, USING

1216
00:47:26,080 --> 00:47:28,000
PHYSIOLOGICALLY RELEVANT

1217
00:47:28,000 --> 00:47:30,360
CONDITIONS AND AGAIN, IN BRIEF,

1218
00:47:30,360 --> 00:47:32,000
WE DEMONSTRATED ALL 3 OF THESE

1219
00:47:32,000 --> 00:47:35,800
MECHANISMS OF IMOWN O DOMINANCE

1220
00:47:35,800 --> 00:47:36,080
DO CONSIDER.

1221
00:47:36,080 --> 00:47:40,480
AND CAN RESULT IN ESSENTIALLY NO

1222
00:47:40,480 --> 00:47:41,360
NEUTRALIZING ANTIBODIES

1223
00:47:41,360 --> 00:47:42,960
DEVELOPING IN SOME CASES AND THE

1224
00:47:42,960 --> 00:47:44,680
RESPONSE TO THAT WAS ESSENTIALLY

1225
00:47:44,680 --> 00:47:46,480
AT THE OTHER GROUPS HAVE

1226
00:47:46,480 --> 00:47:47,680
CONFIRMED THOSE OUTCOMES, THE

1227
00:47:47,680 --> 00:47:50,360
RESPONSE TO THAT TO SOME DEGREE

1228
00:47:50,360 --> 00:47:51,680
WAS, OKAY, FINE IMMUNO DOMINANCE

1229
00:47:51,680 --> 00:47:56,000
IS A REAL PROBLEM, NOW WE'RE

1230
00:47:56,000 --> 00:47:56,520
JUST SAD.

1231
00:47:56,520 --> 00:47:58,640
AND THE KEY THING THERE IS,

1232
00:47:58,640 --> 00:48:00,280
FREQUENTLY TO SOLVE A PROBLEM,

1233
00:48:00,280 --> 00:48:01,040
YOU HAVE TO FIRST UNDERSTAND

1234
00:48:01,040 --> 00:48:02,760
WHAT THE PROBLEM WAS, SO KNOWING

1235
00:48:02,760 --> 00:48:05,640
THAT IMMUNO DOMINANCE WAS AN

1236
00:48:05,640 --> 00:48:06,920
ISSUE, WE DID A SERIES OF

1237
00:48:06,920 --> 00:48:09,280
STUDIES TO TRY AND SEE IF IMMUNO

1238
00:48:09,280 --> 00:48:12,840
DOMINANCE COULD BE MODULATED BY

1239
00:48:12,840 --> 00:48:14,320
DIFFERENT IMMUNOLOGICAL EVENTS

1240
00:48:14,320 --> 00:48:17,240
AND WAWE HAVE FOUND IS THAT BY

1241
00:48:17,240 --> 00:48:18,760
CHANGING THE KINETICS OF THE

1242
00:48:18,760 --> 00:48:23,440
DELIVERY OF ANTIGEN, YOU CAN

1243
00:48:23,440 --> 00:48:25,120
HAVE MASSIVE IMPACTS ON IMMUNO

1244
00:48:25,120 --> 00:48:26,760
DOMINANCE WHERE A CONVENTIONAL

1245
00:48:26,760 --> 00:48:30,880
INJECTION OF HIV ENVELOPE INTO

1246
00:48:30,880 --> 00:48:31,880
MONKEYS GENERALLY GIVES ONLY

1247
00:48:31,880 --> 00:48:34,480
ABOUT 50% OF THE MONKEYS MAKE

1248
00:48:34,480 --> 00:48:35,240
NEUTRALIZING ANTIBODIES

1249
00:48:35,240 --> 00:48:36,480
APPROXIMATE AND IT'S ONLY ABOUT

1250
00:48:36,480 --> 00:48:38,360
AFTER 6 MONTHS OF IMMUNIZATIONS

1251
00:48:38,360 --> 00:48:39,960
BUT IF WE CHANGE THAT TO A SLOW

1252
00:48:39,960 --> 00:48:41,520
DELIVERY SUCH THAT THE EXACT

1253
00:48:41,520 --> 00:48:43,600
SAME AMOUNT OF PROTEIN AND

1254
00:48:43,600 --> 00:48:45,600
ADJUVANT IS DELIVERED, BUT IT'S

1255
00:48:45,600 --> 00:48:46,800
DELIVERED OVER--IT'S SPREAD OUT

1256
00:48:46,800 --> 00:48:49,000
OVER 14 DAYS OR 12 DAYS INSTEAD

1257
00:48:49,000 --> 00:48:56,320
OF A SINGLE INJECTION, THOSE

1258
00:48:56,320 --> 00:48:57,680
ANIMALS NOW MAKE NEUTRALIZING

1259
00:48:57,680 --> 00:48:59,880
EABT BODIES AND THEY MAKE THEM

1260
00:48:59,880 --> 00:49:01,360
FASTER AND OUR MEASUREMENT TO

1261
00:49:01,360 --> 00:49:03,680
THE B-CELL RESPONSES TESTED 2

1262
00:49:03,680 --> 00:49:06,280
IDEAS, 1 WOULD BE THIS HAPPENS

1263
00:49:06,280 --> 00:49:07,320
BECAUSE SOMATIC HYPERMUTATION IS

1264
00:49:07,320 --> 00:49:10,040
BETTER AND YOU JUST HAVE MORE

1265
00:49:10,040 --> 00:49:11,040
AFFINITY MATURATION, MORE

1266
00:49:11,040 --> 00:49:13,760
AFFINITY AND THAT'S WHY YOU END

1267
00:49:13,760 --> 00:49:14,600
UP WITH NEUTRALIZING ANTIBODIES

1268
00:49:14,600 --> 00:49:17,200
OR IT WAS AN IMMUNO DOMINANCE

1269
00:49:17,200 --> 00:49:19,440
PROBLEM OF WHICH B-CELLS GOT

1270
00:49:19,440 --> 00:49:21,240
RECRUITED AND IT TURNED OUT THAT

1271
00:49:21,240 --> 00:49:23,480
THEY ALL POINTED TO THE IMMUNO

1272
00:49:23,480 --> 00:49:26,080
DOMINANCE PROBLEM AND UNDER

1273
00:49:26,080 --> 00:49:27,200
CONVENTIONAL IMMUNIZATION, THERE

1274
00:49:27,200 --> 00:49:29,200
ARE LOW TO NO HIV B-CELLS THAT

1275
00:49:29,200 --> 00:49:33,320
GET RECRUITED INTO THE GERM LINE

1276
00:49:33,320 --> 00:49:34,880
CENTER RESPONSE AT ALL AND THEN

1277
00:49:34,880 --> 00:49:37,120
THEY GET OUTCOME PETEED QUICKLY.

1278
00:49:37,120 --> 00:49:39,320
BUT IN THE SLOW DELIVERY CONTEXT

1279
00:49:39,320 --> 00:49:43,400
WHERE WE HAVE A RESPONSE WE HAVE

1280
00:49:43,400 --> 00:49:44,840
MUCH BETTER RECRUITMENT OF THE

1281
00:49:44,840 --> 00:49:48,200
RARER AND LOWER AFFINITY, HIV

1282
00:49:48,200 --> 00:49:49,200
NEUTRALIZING ANTIBODY CAPACITY

1283
00:49:49,200 --> 00:49:50,560
B-CELLS AND THEN THAT THOSE HAVE

1284
00:49:50,560 --> 00:49:55,440
MORE TIME AND MORE ABILITY TO BE

1285
00:49:55,440 --> 00:49:57,760
KEPT IN A GERMINAL CENTER AND

1286
00:49:57,760 --> 00:50:00,680
NOT BE OUTCOME PETEED AND ATTAIN

1287
00:50:00,680 --> 00:50:01,120
ADDITIONAL AFFINITY.

1288
00:50:01,120 --> 00:50:04,280
AND SOME OF THAT WE THINK HAS TO

1289
00:50:04,280 --> 00:50:06,240
DO WITH ANTIGEN ANTIBODY COMPLEX

1290
00:50:06,240 --> 00:50:08,240
FORMATION AND BETTER RETENTION

1291
00:50:08,240 --> 00:50:09,880
OF ANTIGEN AND WE CAN TRACK ALL

1292
00:50:09,880 --> 00:50:12,880
OF THAT USING LYMPHNODE FINE

1293
00:50:12,880 --> 00:50:13,920
NEEDLE ASPIRATES AND IN THE

1294
00:50:13,920 --> 00:50:18,160
INTEREST OF TIME, I WILL JUMP TO

1295
00:50:18,160 --> 00:50:19,240
THE FINAL PIECE; OKAY WHICH IS 1

1296
00:50:19,240 --> 00:50:25,120
OF THE THINGS WE OBSERVED IN ALL

1297
00:50:25,120 --> 00:50:27,720
THOSE STUDIES CHES THAT THE

1298
00:50:27,720 --> 00:50:28,960
GERMINAL CENTER COULD BEHAVE

1299
00:50:28,960 --> 00:50:30,840
DIFFERENTLY THAN THE SIMPLE

1300
00:50:30,840 --> 00:50:32,240
MODELS ORIGINALLY IN PLACE AND A

1301
00:50:32,240 --> 00:50:37,320
GERMINAL CENTER COULD BE A MUCH

1302
00:50:37,320 --> 00:50:38,840
MORE INCLUSIVE ENVIRONMENT AND

1303
00:50:38,840 --> 00:50:40,960
ALSO COULD EXIST FOR A

1304
00:50:40,960 --> 00:50:41,760
SIGNIFICANTLY LONGER PERIOD OF

1305
00:50:41,760 --> 00:50:43,760
TIME THAN WE THOUGHT.

1306
00:50:43,760 --> 00:50:46,120
WE THOUGHT GERMINAL CENTERS AM

1307
00:50:46,120 --> 00:50:47,840
PEAK AT 2 OR 3 WESTBOUNDS BASED

1308
00:50:47,840 --> 00:50:49,560
ON MOUSE MODELS AND OTHER DATA

1309
00:50:49,560 --> 00:50:51,680
BUT WE HAD BEEN SEEING GERMINAL

1310
00:50:51,680 --> 00:50:52,760
CENTERS STILL AT 8 WEEKS AND

1311
00:50:52,760 --> 00:50:53,960
THAT WAS LONGER THAN WE EXPECTED

1312
00:50:53,960 --> 00:50:57,760
AND SO WE SET UP A STUDY WHICH

1313
00:50:57,760 --> 00:51:00,720
WE JUST RECENTLY PUBLISHED TO

1314
00:51:00,720 --> 00:51:02,400
ASK, WELL, HOW LONG CAN THESE

1315
00:51:02,400 --> 00:51:04,640
GERMINAL CENTERS LAST AFTER A

1316
00:51:04,640 --> 00:51:06,040
PRIMING IMMUNIZATION AND IT USED

1317
00:51:06,040 --> 00:51:07,720
TO BE ABOUT ESSENTIALLY NOTHING

1318
00:51:07,720 --> 00:51:09,680
HAPPENED AFTER A PRIMING

1319
00:51:09,680 --> 00:51:10,600
IMMUNIZATION BECAUSE YOU

1320
00:51:10,600 --> 00:51:11,760
COULDN'T MEASURE ANYTHING IN THE

1321
00:51:11,760 --> 00:51:12,840
BLOOD AND WHAT YOU SHOWED IS

1322
00:51:12,840 --> 00:51:13,800
THAT CERTAINLY THERE ARE THINGS

1323
00:51:13,800 --> 00:51:15,240
IN GOING ON IN THE LYMPHNODE AND

1324
00:51:15,240 --> 00:51:16,520
MAYBE LOTS OF THINGS ARE GOING

1325
00:51:16,520 --> 00:51:19,920
ON IN THE LYMPHNODE.

1326
00:51:19,920 --> 00:51:21,960
SO, WE DID A STUDY THAT WAS AN

1327
00:51:21,960 --> 00:51:23,520
EXERCISE IN PATIENTS SO HERE I'M

1328
00:51:23,520 --> 00:51:24,360
SHOWING YOU LYMPHNODE SAMPLES

1329
00:51:24,360 --> 00:51:28,840
FROM THE SAME ANIMALS,

1330
00:51:28,840 --> 00:51:29,520
LONGITUDINALLY TRACKED OVER TIME

1331
00:51:29,520 --> 00:51:31,800
AND LOOKING AT THE GERMINAL

1332
00:51:31,800 --> 00:51:34,080
B-CELLS AND AT 10 WEEKS POST

1333
00:51:34,080 --> 00:51:36,800
VACCINATION, WE SAW LOTS OF

1334
00:51:36,800 --> 00:51:38,600
GERMINAL B-CELLS THAT WERE

1335
00:51:38,600 --> 00:51:42,360
ENVELOPE SPECIFIC STILL AND AT 4

1336
00:51:42,360 --> 00:51:43,560
MONTHS, POST VACCINATION, THOSE

1337
00:51:43,560 --> 00:51:44,720
GERMINAL CENTERS WERE STILL

1338
00:51:44,720 --> 00:51:47,360
THERE, AND AT 6 MONTHS, THOSE

1339
00:51:47,360 --> 00:51:48,640
GERMINAL CENTERS WERE STILL

1340
00:51:48,640 --> 00:51:51,080
ONGOING EVEN THOUGH WE PROVIDED

1341
00:51:51,080 --> 00:51:53,400
NO NEW ANTIGEN IN THE SYSTEM

1342
00:51:53,400 --> 00:51:54,080
SINCE DAY 12.

1343
00:51:54,080 --> 00:51:54,760
OKAY?

1344
00:51:54,760 --> 00:51:57,560
SO I DON'T--THIS IS JUST

1345
00:51:57,560 --> 00:51:58,360
FANTASTIC.

1346
00:51:58,360 --> 00:51:59,840
THIS WAS REALLY AMAZING THESE

1347
00:51:59,840 --> 00:52:01,520
GERMINAL CENTERS WERE GOING ON

1348
00:52:01,520 --> 00:52:02,960
THIS LONG AND MY POST DOC SAID

1349
00:52:02,960 --> 00:52:04,000
THIS IS TERINCREASE IN BODY,

1350
00:52:04,000 --> 00:52:05,960
THIS EXPERIMENT'S GOING ON

1351
00:52:05,960 --> 00:52:09,240
FOREVER, AND SO WE DID END IT AT

1352
00:52:09,240 --> 00:52:10,440
THAT POINT.

1353
00:52:10,440 --> 00:52:13,520
AND FOR COMPARISON, WE IMMUNIZED

1354
00:52:13,520 --> 00:52:15,200
ANIMALS WITH HIV ENVELOPE WITH

1355
00:52:15,200 --> 00:52:16,840
ALLUM AND WE GOT A PEAK AT ABOUT

1356
00:52:16,840 --> 00:52:18,560
WEEK 3 AND THEN THEY WERE GONE

1357
00:52:18,560 --> 00:52:21,920
BY WEEK 10 BUT IF WE DID THIS

1358
00:52:21,920 --> 00:52:22,600
SLOW DELIVERY IMMUNIZATION,

1359
00:52:22,600 --> 00:52:24,840
AGAIN JUST OVER A COURSE OF 12

1360
00:52:24,840 --> 00:52:27,600
DAYS WITH AN ADJUVANT WE REALLY

1361
00:52:27,600 --> 00:52:30,560
LIKE WHICH WE CAN DISCUSS, WE

1362
00:52:30,560 --> 00:52:32,960
SEE AT WEEK TEN-DOLLAR'S OVER A

1363
00:52:32,960 --> 00:52:34,240
HUNDRED FOLD DIFFERENCE IN THE

1364
00:52:34,240 --> 00:52:36,760
GERMINAL CENTER RESPONSE BETWEEN

1365
00:52:36,760 --> 00:52:38,960
THESE 2, IMMUNIZATION APPROACHES

1366
00:52:38,960 --> 00:52:40,640
AND A HUNDRED FOLD DIFFERENCE IN

1367
00:52:40,640 --> 00:52:42,000
B-CELLS IS A MASSIVE DIFFERENCE

1368
00:52:42,000 --> 00:52:43,680
IN THE AMOUNT OF EVOLUTIONARY

1369
00:52:43,680 --> 00:52:46,200
SPACE THAT CAN BE EXPLORED

1370
00:52:46,200 --> 00:52:47,040
BECAUSE THEY'RE DIVIDING

1371
00:52:47,040 --> 00:52:49,120
APPROXIMATELY ONCE EVERY 4-6

1372
00:52:49,120 --> 00:52:51,680
HOURS AT LEAST BASED ON MOUSE

1373
00:52:51,680 --> 00:52:52,880
MODELS AND HERE'S THE

1374
00:52:52,880 --> 00:52:54,440
QUANTIFICATION OF THE DATA OUT

1375
00:52:54,440 --> 00:52:55,160
TO 6 MONTHS.

1376
00:52:55,160 --> 00:52:57,560
SO 1 CRITICAL QUESTION WAS ARE

1377
00:52:57,560 --> 00:52:59,600
THESE ACTUALLY REAL GERMINAL

1378
00:52:59,600 --> 00:53:00,840
CENTERS, ARE THESE FUNCTIONAL?

1379
00:53:00,840 --> 00:53:03,160
SO WE DID SINGLE CELL

1380
00:53:03,160 --> 00:53:04,240
TRANSCRIPTOMICS AND WE CAN SEE

1381
00:53:04,240 --> 00:53:06,160
THAT THE GERMINAL CENTER B-CELLS

1382
00:53:06,160 --> 00:53:09,000
AT WEEK 3 LOOK SIMILAR TO THE

1383
00:53:09,000 --> 00:53:11,120
GERMINAL CENTER B-CELLS IN WEEK

1384
00:53:11,120 --> 00:53:12,520
29 INCLUDING PROLIFERATION

1385
00:53:12,520 --> 00:53:15,760
MARKERS AND SOMATIC

1386
00:53:15,760 --> 00:53:16,880
HYPERMUTATION, SO, TRANSCRIPT

1387
00:53:16,880 --> 00:53:18,640
ORDER OF MICRONSICS THESE

1388
00:53:18,640 --> 00:53:19,640
B-CELLS LOOK VERY EQUIVALENT

1389
00:53:19,640 --> 00:53:20,840
BETWEEN EARLY AND LATE.

1390
00:53:20,840 --> 00:53:25,400
THEY ARE STILL FUNCTIONAL, THEY

1391
00:53:25,400 --> 00:53:27,360
ARE STILL DIVIDING AND WE SHOW

1392
00:53:27,360 --> 00:53:28,880
THAT THEY ACONTINUE TO

1393
00:53:28,880 --> 00:53:30,960
ACCUMULATE FUNCTIONS SO THEY

1394
00:53:30,960 --> 00:53:33,720
CONTINUE TO ACCUMULATE SOMATIC

1395
00:53:33,720 --> 00:53:36,160
HYPERPUTATION FOR 6 FULL MONTHS.

1396
00:53:36,160 --> 00:53:37,960
BUT REALLY TO SUMMARIZE IT ALL

1397
00:53:37,960 --> 00:53:40,240
IN A SINGLE SLIDE, WE COULD

1398
00:53:40,240 --> 00:53:41,680
TRACK LYNNERAGES OVER 6 MONTHS

1399
00:53:41,680 --> 00:53:43,880
IN NISSAN MALS, SINGLE B-CELL

1400
00:53:43,880 --> 00:53:45,320
LINEAGES BY GOING BACK INTO

1401
00:53:45,320 --> 00:53:46,600
THESE GERMINAL CENTERS OVER AND

1402
00:53:46,600 --> 00:53:48,040
OVER AGAIN AND WE COULD SEE

1403
00:53:48,040 --> 00:53:49,240
THERE WERE LINEAGES THAT STAYED

1404
00:53:49,240 --> 00:53:51,960
IN THESE GERMINAL CENTERS FOR 6

1405
00:53:51,960 --> 00:53:54,400
MONTHS AND THAT THEY WOULD

1406
00:53:54,400 --> 00:53:55,920
UNDERGO AFFINITY MATURATION.

1407
00:53:55,920 --> 00:53:58,560
HERE'S 1 THAT'S PRETTY STRIKING

1408
00:53:58,560 --> 00:54:00,880
EXAMPLE OF ESSENTIALLY

1409
00:54:00,880 --> 00:54:01,720
UNDETECTABLE AFFINITY AT TIME

1410
00:54:01,720 --> 00:54:03,840
POINTS AND NOW A THOUSAND FOLD

1411
00:54:03,840 --> 00:54:07,360
IMPROVEMENTS IN AFFINITY BY 6

1412
00:54:07,360 --> 00:54:07,720
MONTHS LATER.

1413
00:54:07,720 --> 00:54:09,560
THAT DOES HAVE PRACTICAL

1414
00:54:09,560 --> 00:54:10,360
SMLICATIONS BECAUSE WE CAN

1415
00:54:10,360 --> 00:54:11,680
ACTUALLY SEE FOR THE FIRST TIME

1416
00:54:11,680 --> 00:54:19,640
EVER, THAT THESE ANIMALS

1417
00:54:19,640 --> 00:54:21,640
ACTUALLY DEVELOPED AUTOLOGOUS

1418
00:54:21,640 --> 00:54:23,880
BEFORE, THIS INDICATING THE

1419
00:54:23,880 --> 00:54:25,840
B-CELLS WERE FUNCTIONAL BEFORE

1420
00:54:25,840 --> 00:54:26,040
BOOSTER.

1421
00:54:26,040 --> 00:54:27,440
SO IMMUNOLOGICALLY THIS IS

1422
00:54:27,440 --> 00:54:28,160
REALLY FASCINATING BECAUSE BACK

1423
00:54:28,160 --> 00:54:29,680
TO THE ENVELOPE CALCULATIONS

1424
00:54:29,680 --> 00:54:33,000
WOULD BE THAT THAT'S ABOUT 750

1425
00:54:33,000 --> 00:54:34,640
CELL DIVISIONS THAT THESE

1426
00:54:34,640 --> 00:54:35,920
GERMINAL CENTER B-CELLS ARE

1427
00:54:35,920 --> 00:54:36,880
UNDER GOING OVER 6 MONTHS.

1428
00:54:36,880 --> 00:54:39,840
SO I THINK THAT MEANS WE DON'T

1429
00:54:39,840 --> 00:54:41,800
REALLY UNDERSTAND THE ABILITY OF

1430
00:54:41,800 --> 00:54:43,560
THESE CELLS TO PROLIFERATE THE

1431
00:54:43,560 --> 00:54:48,360
WAY WE THOUGHT AND THAT THESE

1432
00:54:48,360 --> 00:54:49,000
GERMINAL CENTERS ARE FUNCTIONAL

1433
00:54:49,000 --> 00:54:51,960
THEY CAN HAPPEN IN RESPONSE TO A

1434
00:54:51,960 --> 00:54:53,240
PRIMING IMMUNIZATION AND THAT

1435
00:54:53,240 --> 00:54:54,640
ESSENTIALLY PATIENTS IN A

1436
00:54:54,640 --> 00:54:56,240
VACCINE STRATEGY CAN HAVE LOTS

1437
00:54:56,240 --> 00:54:57,560
OF BENEFITS WHEN YOU'RE TRYING

1438
00:54:57,560 --> 00:54:58,720
TO GENERATE RESPONSES TO

1439
00:54:58,720 --> 00:55:01,760
DIFFICULT TARGETS, AND THIS WAS

1440
00:55:01,760 --> 00:55:04,080
LED BY A FANTASTIC INSTRUCTOR

1441
00:55:04,080 --> 00:55:08,120
JMPLET H. LEE WHO IS CAMERA SHY,

1442
00:55:08,120 --> 00:55:15,320
AN AMAZING SCIENTIST AND HARRY

1443
00:55:15,320 --> 00:55:17,480
SUTTON, DID SOME OF THE WORK,

1444
00:55:17,480 --> 00:55:19,720
AND JUST TO TIE IT BACK TO THE

1445
00:55:19,720 --> 00:55:20,880
COVID WORK, WE'RE NOT SHOWING

1446
00:55:20,880 --> 00:55:22,200
ANYTHING NEW HERE IN OUR

1447
00:55:22,200 --> 00:55:22,800
EXPERIMENTAL DATA, I THINK THE

1448
00:55:22,800 --> 00:55:25,120
DAILY BASIS AT IS CONSISTENT

1449
00:55:25,120 --> 00:55:28,200
WITH GERMINAL CENTERS IN

1450
00:55:28,200 --> 00:55:29,240
SARS-COV-2 INFECTED INDIVIDUALS

1451
00:55:29,240 --> 00:55:30,240
6 MONTHS LATER SUGGESTING THAT

1452
00:55:30,240 --> 00:55:34,200
IS A NORMAL BIOLOGICAL PROCESS

1453
00:55:34,200 --> 00:55:36,480
AND I THINK [INDISCERNIBLE] HA

1454
00:55:36,480 --> 00:55:38,560
BETA THAT GERMINAL CENTERS ARE

1455
00:55:38,560 --> 00:55:39,520
DETECTABLE IN PEOPLE 6 MONTHS

1456
00:55:39,520 --> 00:55:41,880
LATER WE THINK YOU DON'T HAVE TO

1457
00:55:41,880 --> 00:55:43,240
INVOKE RNA EXPRESSION FOR 6

1458
00:55:43,240 --> 00:55:44,560
MONTHS TO EXPLAIN THOSE RESULTS

1459
00:55:44,560 --> 00:55:46,240
BUT THEY COULD EXPLAIN WHY

1460
00:55:46,240 --> 00:55:48,640
MEMORY B-CELLS ARE INCREASING

1461
00:55:48,640 --> 00:55:49,600
OVER A 6 MONTH PERIOD.

1462
00:55:49,600 --> 00:55:53,320
IT MAY ALSO BE TRUE FOR ADEN O

1463
00:55:53,320 --> 00:55:55,400
VIRAL VECTORS BUT THESE KINETICS

1464
00:55:55,400 --> 00:55:57,400
ARE DIFFERENT FROM THESE

1465
00:55:57,400 --> 00:55:58,600
KINETICS SUGGESTING THAT THESE

1466
00:55:58,600 --> 00:55:59,760
DIFFERENT PROCESSES IN THE

1467
00:55:59,760 --> 00:56:03,080
GERMINAL CENTER, RIGHT AND LUNG

1468
00:56:03,080 --> 00:56:04,600
GERMINAL CENTERS MAY HAPPEN IN

1469
00:56:04,600 --> 00:56:05,760
DIFFERENT WAYS WITH DIFFERENT

1470
00:56:05,760 --> 00:56:08,080
PLATFORMS SO EVERYTHING I SHOWED

1471
00:56:08,080 --> 00:56:09,960
ABOUT THE HIV STUFF IS

1472
00:56:09,960 --> 00:56:11,800
COLLABORATIVE SO I DID JUSTMENT

1473
00:56:11,800 --> 00:56:13,560
TO HIGHLIGHT THAT THAT'S OUR

1474
00:56:13,560 --> 00:56:15,120
CHILD CONSORTIUM LED BY DENNIS

1475
00:56:15,120 --> 00:56:18,520
BURREDON, ALL OF THE ANTIGENS

1476
00:56:18,520 --> 00:56:19,480
ARE PROVIDED BY BILL

1477
00:56:19,480 --> 00:56:21,400
[INDISCERNIBLE] AND MOST OF OUR

1478
00:56:21,400 --> 00:56:25,360
WORK IS IN CLOSE COLLABORATION

1479
00:56:25,360 --> 00:56:26,600
BILL AND ADAPTED RUE AND WITH

1480
00:56:26,600 --> 00:56:28,000
THAT I WILL STOP AND TAKE ANY

1481
00:56:28,000 --> 00:56:30,240
QUESTIONS, I KNOW I WENT A SMIJ

1482
00:56:30,240 --> 00:56:33,920
LONG, YEAH, THANKS IF ARE YOUR

1483
00:56:33,920 --> 00:56:34,440
ATTENTION.

1484
00:56:34,440 --> 00:56:35,320
>>GREAT, THAT WAS
WONDERFUL

1485
00:56:35,320 --> 00:56:37,480
SHANE AND I DO WANT TO EMPHASIZE

1486
00:56:37,480 --> 00:56:38,760
FOR PEOPLE IN THE AUDIENCE THAT

1487
00:56:38,760 --> 00:56:44,520
PART OF THE REASON WHY SHANE AND

1488
00:56:44,520 --> 00:56:45,760
ALEX AND OTHERS ON THE TEAM

1489
00:56:45,760 --> 00:56:47,480
THERE HAVE BEEN ABLE TO REALLY

1490
00:56:47,480 --> 00:56:49,120
UNCOVER THESE AND STUDY THESE IS

1491
00:56:49,120 --> 00:56:51,280
JUST BECAUSE OF THE FUNDAMENT

1492
00:56:51,280 --> 00:56:53,840
AMILLIO WORK ON TFH AND GERMINAL

1493
00:56:53,840 --> 00:56:54,840
CENTER BIOLOGY THAT HE DESCRIBED

1494
00:56:54,840 --> 00:56:56,760
AT THE END AND WE HAVE A LOT OF

1495
00:56:56,760 --> 00:56:58,160
QUESTIONS, I WILL TRY TO GET

1496
00:56:58,160 --> 00:56:58,480
THROUGH THEM.

1497
00:56:58,480 --> 00:57:01,080
THERE WERE A COUPLE OF QUESTIONS

1498
00:57:01,080 --> 00:57:04,120
YOU PROBABLY--SOME ADDRESSED AT

1499
00:57:04,120 --> 00:57:07,840
THE END ON WHY--WHAT IS IT ABOUT

1500
00:57:07,840 --> 00:57:09,160
MRNA VACCINES THAT YOU THINK

1501
00:57:09,160 --> 00:57:14,240
THAT GIVES THIS LONG RESPONSE

1502
00:57:14,240 --> 00:57:14,600
PARTICULARLY.

1503
00:57:14,600 --> 00:57:17,280
IS IT THAT THEY'RE BETTER AT TFH

1504
00:57:17,280 --> 00:57:20,560
CELLS OR CD4 CELL RESPONSES AND

1505
00:57:20,560 --> 00:57:23,720
WHY IS IT OR WHY DO YOU THINK?

1506
00:57:23,720 --> 00:57:25,680
>>IT'S DEFINITELY--THEY
ARE

1507
00:57:25,680 --> 00:57:28,360
FANTASTIC AT PRIMING CDFOUR

1508
00:57:28,360 --> 00:57:30,680
RESPONSES AND FOR EXAMPLE, RBD

1509
00:57:30,680 --> 00:57:33,160
ALONE IS QUITE SMALL AND DIDN'T

1510
00:57:33,160 --> 00:57:36,480
HAVE GREAT T-CELL EPITOPES IN IT

1511
00:57:36,480 --> 00:57:39,000
AND YET BIOENTECH USING RBD WAS

1512
00:57:39,000 --> 00:57:41,600
ABLE TO ILLICIT QUITE ROBUST CD4

1513
00:57:41,600 --> 00:57:43,880
RESPONSE AND THAT'S 1 KEY PIECE

1514
00:57:43,880 --> 00:57:45,640
OF DATA FROM ME DEMONSTRATING

1515
00:57:45,640 --> 00:57:46,040
THAT.

1516
00:57:46,040 --> 00:57:50,480
AND IN TERMS OF KINETICS, WE

1517
00:57:50,480 --> 00:57:52,880
THINK THAT RNA VACCINES ARE

1518
00:57:52,880 --> 00:57:55,120
PROBABLY MIMICKING THESE TYPES

1519
00:57:55,120 --> 00:57:57,600
OF KINETICS WHERE THERE IS

1520
00:57:57,600 --> 00:57:58,760
ANTIGEN EXPRESSION FOR AT LEAST

1521
00:57:58,760 --> 00:58:02,160
A PERIOD OF A COUPLE OF WEEKS

1522
00:58:02,160 --> 00:58:04,880
AND THAT THAT IS INVOKING THESE

1523
00:58:04,880 --> 00:58:07,480
TYPES OF MECHANISMS THAT WE'RE

1524
00:58:07,480 --> 00:58:09,240
TALKING ABOUT THAT THEN ALLOW

1525
00:58:09,240 --> 00:58:10,080
FOR SUSTAINED GERMINAL CENTERS

1526
00:58:10,080 --> 00:58:12,400
AND I THINK REALLY WHAT WE'RE

1527
00:58:12,400 --> 00:58:14,960
DEALING WITH HERE ARE THE IMMUNE

1528
00:58:14,960 --> 00:58:15,920
SYSTEMS EVOLVE FOR MILLIONS OF

1529
00:58:15,920 --> 00:58:21,840
YEARS TO TRY AND RECOGNIZE

1530
00:58:21,840 --> 00:58:24,400
PATHOGENS SO IT'S NOT--LET'S SEE

1531
00:58:24,400 --> 00:58:29,000
IF I CAN--IT'S REALLY USED TO

1532
00:58:29,000 --> 00:58:35,520
NOT BEING EXPOSED TO A BOLUS

1533
00:58:35,520 --> 00:58:43,200
IMMUNIZATION, RIGHT?

1534
00:58:43,200 --> 00:58:45,560
BUT INSTEAD SEEING IT OVER TIME

1535
00:58:45,560 --> 00:58:49,080
MECHANISMS GET INVOKED AND I

1536
00:58:49,080 --> 00:58:50,520
WILL--GET INVOKED AND I THINK

1537
00:58:50,520 --> 00:58:52,760
RNA RACK SEENS ARE EXPRESSING

1538
00:58:52,760 --> 00:58:54,400
ANTIGEN OVER SOME PERIOD OF

1539
00:58:54,400 --> 00:58:54,600
TIME.

1540
00:58:54,600 --> 00:58:59,120
SCOTT BOYD HAS DATA ON HA AND

1541
00:58:59,120 --> 00:59:00,360
THAT THOSE RESULTS IN THE

1542
00:59:00,360 --> 00:59:03,320
ABILITY TO SUPER THESE LONGER

1543
00:59:03,320 --> 00:59:06,360
GERMINAL CENTERS IN OUR CASE,

1544
00:59:06,360 --> 00:59:09,960
THEY WILL SHOW, THE RESULTS IN A

1545
00:59:09,960 --> 00:59:10,880
DRAMATIC ANTIGEN CAPTURE AND

1546
00:59:10,880 --> 00:59:15,080
IT'S A BEAUTIFUL IMAGES FROM

1547
00:59:15,080 --> 00:59:17,200
DALE URBAN'S LAB WHERE WE LOOK

1548
00:59:17,200 --> 00:59:19,400
AT WHOLE CLARIFIED LYMPHNODES IN

1549
00:59:19,400 --> 00:59:22,040
THE MONKEYS WITH A FLUORESCENT

1550
00:59:22,040 --> 00:59:23,960
ANTIGEN 2 KAYS AFTER

1551
00:59:23,960 --> 00:59:25,040
CONVENTIONAL SYRINGE.

1552
00:59:25,040 --> 00:59:27,960
THIS IS A VIDEO, THERE ARE BITS

1553
00:59:27,960 --> 00:59:29,280
OF ANTIGEN THERE COMPARED TO

1554
00:59:29,280 --> 00:59:31,560
SLOW DELIVERY OF THE EXACT SAME

1555
00:59:31,560 --> 00:59:33,200
TOTAL AMOUNT OF ANTIGEN ASK

1556
00:59:33,200 --> 00:59:34,600
THERE'S ENORMOUS DIFFERENCE IN

1557
00:59:34,600 --> 00:59:37,080
THE ANTIGEN TO BE CAPTURED AND

1558
00:59:37,080 --> 00:59:39,040
GO TO GERMINAL CENTERS IF YOU

1559
00:59:39,040 --> 00:59:41,400
GET THE IMMUNE SYSTEM AHEAD

1560
00:59:41,400 --> 00:59:43,640
START AND SOME ADDITIONAL TIME.

1561
00:59:43,640 --> 00:59:45,280
YEAH, GO AHEAD, PAM.

1562
00:59:45,280 --> 00:59:47,720
>>OH, NO, I WAS REMINDED
TO

1563
00:59:47,720 --> 00:59:53,000
TELL PEOPLE THAT THE CME CODE IS

1564
00:59:53,000 --> 00:59:55,240
44465 AND JUST A LOT OF

1565
00:59:55,240 --> 00:59:56,480
QUESTIONS COMING IN.

1566
00:59:56,480 --> 00:59:59,160
SO 1 FROM AMANDA HENNING, ARE

1567
00:59:59,160 --> 01:00:01,160
YOU CONCERNED AT ALL ABOUT

1568
01:00:01,160 --> 01:00:03,960
INCREASED RISK OF LYMPHOMA

1569
01:00:03,960 --> 01:00:06,080
DEVELOPMENT WITH LONG GERMINAL

1570
01:00:06,080 --> 01:00:08,120
CENTER ACTIVITY AND AWLINGS FROM

1571
01:00:08,120 --> 01:00:08,800
STEPHEN [INDISCERNIBLE] 2 PEOPLE

1572
01:00:08,800 --> 01:00:14,240
WITH THE SAME QUESTION.

1573
01:00:14,240 --> 01:00:15,720
>>HMM, YOU KNOW THAT GOT
BUMPY

1574
01:00:15,720 --> 01:00:17,560
THERE SO I WILL PAUSE, CAN YOU

1575
01:00:17,560 --> 01:00:23,080
ASK THE QUESTION AGAIN?

1576
01:00:23,080 --> 01:00:23,960
>>YES, SORRY.

1577
01:00:23,960 --> 01:00:26,000
ARE YOU CONCERNED ABOUT A

1578
01:00:26,000 --> 01:00:28,720
POSSIBLE RISK OF INCREASE

1579
01:00:28,720 --> 01:00:30,920
DEVELOPMENT OR AUTOIMMUNITY WITH

1580
01:00:30,920 --> 01:00:32,600
MORE PROLONGED GERMINAL CENTER

1581
01:00:32,600 --> 01:00:33,080
ACTIVITY.

1582
01:00:33,080 --> 01:00:39,560
>>YEAH, WE ABSOLUTELY
HAVE TO

1583
01:00:39,560 --> 01:00:41,200
KEEP THAT IN MIND.

1584
01:00:41,200 --> 01:00:43,000
CLEARLY THESE RESPONSES CAN GO

1585
01:00:43,000 --> 01:00:44,960
ON DRAMATICALLY LONGER THAN WE

1586
01:00:44,960 --> 01:00:47,240
WERE GENUINELY THINKING AND

1587
01:00:47,240 --> 01:00:49,920
AGAIN, I THINK WHAT WE'RE DOING

1588
01:00:49,920 --> 01:00:52,160
IS ACTUAL NORMAL BIOLOGY AND I

1589
01:00:52,160 --> 01:00:55,200
THINK THIS IS PRETTY COMMON IF

1590
01:00:55,200 --> 01:00:58,000
NOT NORMAL EVEN AFTER VIRAL

1591
01:00:58,000 --> 01:00:59,400
INFECTIONS AND OTHER EXPOSURES,

1592
01:00:59,400 --> 01:01:03,960
AGAIN GOING BACK TO SEEING THESE

1593
01:01:03,960 --> 01:01:05,440
LUNG GERMINAL CENTERS AFTER

1594
01:01:05,440 --> 01:01:06,360
REMARKABLE CASES OF COVID-19.

1595
01:01:06,360 --> 01:01:09,000
I THINK THIS IS PROBABLY A

1596
01:01:09,000 --> 01:01:13,280
PRETTY NORMAL BACKGROUND EVENT

1597
01:01:13,280 --> 01:01:14,600
IN HUMANS AND THAT VACCINES MAY

1598
01:01:14,600 --> 01:01:16,320
BE ABLE TO ENGAGE THIS IN A

1599
01:01:16,320 --> 01:01:18,040
BETTER WAY SO THAT AGAIN, YOU

1600
01:01:18,040 --> 01:01:20,040
GET THINGS LIKE OMICRON

1601
01:01:20,040 --> 01:01:22,400
RECOGNITION FROM A VACCINE THAT

1602
01:01:22,400 --> 01:01:24,280
DOESN'T ACTUALLY INCLUDE OMICRON

1603
01:01:24,280 --> 01:01:27,320
SEQUENCES BUT YEAH, IT'S A GOOD

1604
01:01:27,320 --> 01:01:27,960
POINT.

1605
01:01:27,960 --> 01:01:28,240
>>OKAY.

1606
01:01:28,240 --> 01:01:29,600
ANOTHER QUESTION, MOST OF YOUR

1607
01:01:29,600 --> 01:01:34,360
WORK, THIS IS FROM

1608
01:01:34,360 --> 01:01:36,120
[INDISCERNIBLE] ON SARS-COV-2

1609
01:01:36,120 --> 01:01:37,280
INDICATES THAT THE IMMUNE

1610
01:01:37,280 --> 01:01:39,040
RESPONSE TO THE VIRUS IS

1611
01:01:39,040 --> 01:01:41,000
EXPECTED AND EXPECTED WITH TB

1612
01:01:41,000 --> 01:01:42,480
INTERACTIONS BUT THIS

1613
01:01:42,480 --> 01:01:44,520
INFECTION'S BEEN UNLIKE ANY

1614
01:01:44,520 --> 01:01:44,960
INFECTION WE HAVE.

1615
01:01:44,960 --> 01:01:50,080
DO YOU THINK IT'S

1616
01:01:50,080 --> 01:01:50,720
IMMUNOLOGICALLY DIFFERENT OR IS

1617
01:01:50,720 --> 01:01:54,920
IT THE VIRUS THAT'S DIFFERENT?

1618
01:01:54,920 --> 01:01:58,160
>>I THINK IT'S MORE THAN
1

1619
01:01:58,160 --> 01:01:58,360
THING.

1620
01:01:58,360 --> 01:02:01,960
ANY SITUATION WHERE YOU HAVE A

1621
01:02:01,960 --> 01:02:03,680
PROBLEM THAT'S BECOME AS VAST AS

1622
01:02:03,680 --> 01:02:04,160
COVID-19.

1623
01:02:04,160 --> 01:02:13,240
IT'S NOT JUST 1 THING.

1624
01:02:13,240 --> 01:02:16,800
I ALWAYS--SO, I SAID FOR QUITE A

1625
01:02:16,800 --> 01:02:19,200
WHILE LOOK THIS VIRUS' SUPER

1626
01:02:19,200 --> 01:02:21,640
POWER IS THAT IT'S INCREDIBLY

1627
01:02:21,640 --> 01:02:24,560
GOOD AT EVADING INNATE IMMUNITY.

1628
01:02:24,560 --> 01:02:26,320
IT'S VERY SILENT ANYBODY THAT

1629
01:02:26,320 --> 01:02:28,520
CAN HAVE CAUSE AND EFFECT OF

1630
01:02:28,520 --> 01:02:30,440
DISEASE HAS TO HAVE SOME GOOD

1631
01:02:30,440 --> 01:02:32,680
IMMUNE EVASION TRICK AND THIS

1632
01:02:32,680 --> 01:02:36,520
VIRUS IS UNUSUALLY GOOD AT BEING

1633
01:02:36,520 --> 01:02:39,400
SILENT TO THE INNATE IMMUNITY.

1634
01:02:39,400 --> 01:02:39,760
RIGHT?

1635
01:02:39,760 --> 01:02:43,240
THAT'S WHY YOU HAVE ASYMPTOMATIC

1636
01:02:43,240 --> 01:02:45,320
AND PRESYMPTOMATIC AND PEOPLE

1637
01:02:45,320 --> 01:02:48,040
ARE TRANSMITTING LARGE AMOUNTS

1638
01:02:48,040 --> 01:02:50,040
OF VIRUS WITHOUT KNOWING THEY'RE

1639
01:02:50,040 --> 01:02:53,280
SICK, THAT'S BECAUSE THIS VIRUS

1640
01:02:53,280 --> 01:02:54,160
AVOIDS TRIGGERING INNATE

1641
01:02:54,160 --> 01:02:55,840
IMMUNITY FOR I LONG TIME AND

1642
01:02:55,840 --> 01:02:57,600
THAT DOES HAVE IMPLICATIONS ON

1643
01:02:57,600 --> 01:02:58,560
THE ADAPTIVE IMMUNE RESPONSE AND

1644
01:02:58,560 --> 01:03:00,280
THE AABILITY OF THE ADAPTIVE

1645
01:03:00,280 --> 01:03:03,640
IMMUNE RESPONSE TO REPLY AND IN

1646
01:03:03,640 --> 01:03:06,160
A PAPER I DIDN'T TALK ABOUT, YOU

1647
01:03:06,160 --> 01:03:08,520
KNOW WE TRIED--WE COMPARED

1648
01:03:08,520 --> 01:03:09,800
HOSPITALIZED VERSUS

1649
01:03:09,800 --> 01:03:11,040
NONHOSPITALLIZED PATIENTS AND

1650
01:03:11,040 --> 01:03:13,200
OUR INTERPRETATION OF THE DATA

1651
01:03:13,200 --> 01:03:15,160
WAS THAT IT'S PROBABLY PEOPLE

1652
01:03:15,160 --> 01:03:18,920
WHO HAVE A RELATIVELY LATE AND

1653
01:03:18,920 --> 01:03:20,640
SLOW INNATE IMMUNE RESPONSE THAT

1654
01:03:20,640 --> 01:03:23,000
ARE THE PEOPLE ARE AT HIGHEST

1655
01:03:23,000 --> 01:03:24,600
RISK FOR HOSPITALIZATION BECAUSE

1656
01:03:24,600 --> 01:03:26,560
WHAT WE'RE SEEING IS PEOPLE IN

1657
01:03:26,560 --> 01:03:28,720
THE HOSPITAL WITHOUT DETECTABLE

1658
01:03:28,720 --> 01:03:30,360
CD4 OR 8 T-CELL RESPONSES

1659
01:03:30,360 --> 01:03:32,240
SUGGESTING THAT YOUR ADAPTIVE

1660
01:03:32,240 --> 01:03:33,400
IMMUNE RESPONSE DOESN'T JUST

1661
01:03:33,400 --> 01:03:35,480
START UNTIL THE INNATE IMMUNE

1662
01:03:35,480 --> 01:03:36,160
RESPONSE, RIGHT?

1663
01:03:36,160 --> 01:03:38,520
YOU NEED THAT INNATE IMMUNE

1664
01:03:38,520 --> 01:03:41,000
SIGNAL SO THIS DELAY IN THE

1665
01:03:41,000 --> 01:03:42,640
INNATE HAS THIS DOWN STREAM

1666
01:03:42,640 --> 01:03:44,800
LARGE IMPACT ON THE WAY IN THE

1667
01:03:44,800 --> 01:03:46,240
ADAPTIVE WHICH THE OLDER YOU

1668
01:03:46,240 --> 01:03:51,520
ARE, IS MORE LIKELY TO HAPPEN

1669
01:03:51,520 --> 01:03:52,960
AND CAN PROBABLY BE A MAJOR

1670
01:03:52,960 --> 01:03:55,720
CAUSE OF MUCH OF THOSE PROBLEMS.

1671
01:03:55,720 --> 01:03:57,200
CERTAINLY NOW I THINK WE ALL

1672
01:03:57,200 --> 01:03:58,880
FINALLY RECOGNIZE THAT THE OTHER

1673
01:03:58,880 --> 01:04:00,960
SUPER POWER OF THIS VIRUS IS

1674
01:04:00,960 --> 01:04:02,720
VARIANTS AND IT'S ABILITY TO

1675
01:04:02,720 --> 01:04:05,480
MUTATE AND IT'S INCREDIBLY

1676
01:04:05,480 --> 01:04:05,760
FRUSTRATING.

1677
01:04:05,760 --> 01:04:08,800
I THINK SOME OF THAT WASN'T

1678
01:04:08,800 --> 01:04:09,760
APPARENT EARLY ON BECAUSE IT

1679
01:04:09,760 --> 01:04:11,160
DOESN'T SHOW THAT MUCH DIVERSITY

1680
01:04:11,160 --> 01:04:13,480
BUT IT'S SHOWN THAT IF IT

1681
01:04:13,480 --> 01:04:14,200
DOES--GIVEN THE ABILITY TO

1682
01:04:14,200 --> 01:04:15,600
IBT--INTEGRATE FECT OVER A

1683
01:04:15,600 --> 01:04:16,080
BILLION PEOPLE, RIGHT?

1684
01:04:16,080 --> 01:04:18,520
YOU ROLL THE DICE THAT MANY

1685
01:04:18,520 --> 01:04:19,400
TIMES WITH SEQUENCE EVOLUTION OF

1686
01:04:19,400 --> 01:04:23,040
THE VIRUS AND IT CAN COME UP

1687
01:04:23,040 --> 01:04:25,800
WITH WAYS TO EVADE QUITE A

1688
01:04:25,800 --> 01:04:27,640
VARIETY OF NEUTRALIZING

1689
01:04:27,640 --> 01:04:27,960
ANTIBODIES.

1690
01:04:27,960 --> 01:04:31,760
>>I THINK THIS IS A
RELATED

1691
01:04:31,760 --> 01:04:33,640
QUESTION BUT IT'S ON YOUR

1692
01:04:33,640 --> 01:04:34,680
INTERPRETATION OF WHY THE

1693
01:04:34,680 --> 01:04:36,880
VACCINES DON'T HAVE A

1694
01:04:36,880 --> 01:04:38,120
SIGNIFICANT IMPACT ON

1695
01:04:38,120 --> 01:04:42,680
TRANSMISSION AS OPPOSE TO SEVERE

1696
01:04:42,680 --> 01:04:43,040
ILLNESS.

1697
01:04:43,040 --> 01:04:45,440
>>THEY DO HAVE A
SIGNIFICANT

1698
01:04:45,440 --> 01:04:48,800
IMPACT ON TRANSMISSION, I MEAN

1699
01:04:48,800 --> 01:04:49,720
TRANSMISSION IN THE

1700
01:04:49,720 --> 01:04:50,680
EPIDEMIOLOGICAL STUDIES I'M

1701
01:04:50,680 --> 01:04:53,200
FAMILIAR WITH, TRANSMISSION WAS

1702
01:04:53,200 --> 01:04:56,640
REDUCED 50-75% IN VACCINATED

1703
01:04:56,640 --> 01:04:57,600
COMPARED TO UNVACCINATED WHICH

1704
01:04:57,600 --> 01:05:00,360
YOU KNOW WE START MULTIPLYING

1705
01:05:00,360 --> 01:05:03,040
THAT ACROSS POPULATIONS, THAT IS

1706
01:05:03,040 --> 01:05:03,360
SUBSTANTIAL.

1707
01:05:03,360 --> 01:05:06,920
I DO THINK THE VIRUS, THERE'S

1708
01:05:06,920 --> 01:05:08,200
BEEN PLENTY EVALUATION PROCESS

1709
01:05:08,200 --> 01:05:09,800
EVIDENCE THAT THE VIRUS EVOLVED

1710
01:05:09,800 --> 01:05:12,840
TO BE MOAGHT MORE INFECTIOUS AND

1711
01:05:12,840 --> 01:05:14,320
HAVE HIGHER TITERS, IT IS HARDER

1712
01:05:14,320 --> 01:05:16,440
AND HARDER AS TIME HAS GONE ON

1713
01:05:16,440 --> 01:05:17,720
TO PREVENT TRANSMISSION IS

1714
01:05:17,720 --> 01:05:19,440
BECAUSE IT'S BECOME AN EVEN

1715
01:05:19,440 --> 01:05:21,760
FASTER VIRUS AT TRANSMITTING.

1716
01:05:21,760 --> 01:05:23,480
FOR THE ANCESTRAL STRAIN IT WAS

1717
01:05:23,480 --> 01:05:26,120
REASONABLE TO EXPECT SOME IMPACT

1718
01:05:26,120 --> 01:05:29,400
ON TRANSMISSION BECAUSE THERE

1719
01:05:29,400 --> 01:05:30,680
WAS A SEVERAL DAY WINDOW THERE

1720
01:05:30,680 --> 01:05:33,440
FOR THAT TO HAPPEN AND THAT'S

1721
01:05:33,440 --> 01:05:36,680
GOTTEN COMPRESSED MORE OVER

1722
01:05:36,680 --> 01:05:37,080
TIME.

1723
01:05:37,080 --> 01:05:38,640
>>SOMEONE'S ASKED, DO YOU
KNOW

1724
01:05:38,640 --> 01:05:39,800
ANYTHING ABOUT THE ENZYME

1725
01:05:39,800 --> 01:05:41,320
PATHWAYS THAT CLEARS THE

1726
01:05:41,320 --> 01:05:44,000
MODIFIED RNA IN THE COVID

1727
01:05:44,000 --> 01:05:44,280
VACCINES?

1728
01:05:44,280 --> 01:05:46,760
>>NO, IT'S A GREAT
QUESTION.

1729
01:05:46,760 --> 01:05:49,960
I MEAN, THE STANDARD STATEMENTS

1730
01:05:49,960 --> 01:05:51,840
BY BOTH MODERNA AND PFIZER HAVE

1731
01:05:51,840 --> 01:05:54,600
BEEN THAT THE RNA IS DETECTABLE

1732
01:05:54,600 --> 01:05:58,240
1 OR 2 DAYS POST IMMUNIZATION.

1733
01:05:58,240 --> 01:06:00,560
THERE HASN'T BEEN GREAT

1734
01:06:00,560 --> 01:06:02,400
LITERATURE PUBLISHED BY THEM,

1735
01:06:02,400 --> 01:06:03,720
WELL THERE HASN'T BEEN

1736
01:06:03,720 --> 01:06:07,600
LITERATURE PUBLISHED BY THEM ON

1737
01:06:07,600 --> 01:06:11,160
THOSE TOPICS AND I THINK THE

1738
01:06:11,160 --> 01:06:13,840
DATA FROM SCOTT BOYD WHERE HE

1739
01:06:13,840 --> 01:06:18,120
SHOWS IN CORE LYMPHNODE BIOPSIES

1740
01:06:18,120 --> 01:06:19,840
IN HUMANS DETECTABLE RNA 2 WEEKS

1741
01:06:19,840 --> 01:06:24,200
AND 4 WEEKS POST IMMUNIZATION

1742
01:06:24,200 --> 01:06:25,840
SUGGESTS AND PROTEIN SUGGESTS

1743
01:06:25,840 --> 01:06:27,920
THERE MAY BE FUNCTIONAL RNA FOR

1744
01:06:27,920 --> 01:06:31,200
AT LEAST THAT AMOUNT OF TIME AND

1745
01:06:31,200 --> 01:06:32,480
AND MAY SUGGEST THAT THE

1746
01:06:32,480 --> 01:06:34,200
DEGRADATION OF THE RNA, THE

1747
01:06:34,200 --> 01:06:38,440
MODIFIED RNA IS SLOWER THAN

1748
01:06:38,440 --> 01:06:39,200
INITIALLY THOUGHT, YEAH.

1749
01:06:39,200 --> 01:06:40,120
BUT I DON'T KNOW WHAT THE

1750
01:06:40,120 --> 01:06:40,680
PATHWAYS ARE.

1751
01:06:40,680 --> 01:06:51,120
THATYA A GOOD QUESTION.

1752
01:07:10,640 --> 01:07:16,560
>>I THINK IT REALLY
HIGHLIGHTS

1753
01:07:16,560 --> 01:07:19,680
THE CHALLENGES OF LOCAL TISSUE

1754
01:07:19,680 --> 01:07:20,120
RESPONSES, RIGHT?

1755
01:07:20,120 --> 01:07:22,320
THIS IS CLEARLY A VIRUS THAT

1756
01:07:22,320 --> 01:07:23,520
DOES HAVE ORAL INFECTIONS AND SO

1757
01:07:23,520 --> 01:07:28,160
YOU WOULD LOVE TO KNOW WHAT ARE

1758
01:07:28,160 --> 01:07:30,640
THE B-CELL AND T-CELL RESPONSES

1759
01:07:30,640 --> 01:07:31,960
IN THAT TISSUE, RIGHT?

1760
01:07:31,960 --> 01:07:35,800
THAT'S A HARD QUESTION, THAT IS

1761
01:07:35,800 --> 01:07:38,360
NOT A HUMAN SITE THAT'S EASY TO

1762
01:07:38,360 --> 01:07:41,640
SAMPLE AND THERE IS SOME ABILITY

1763
01:07:41,640 --> 01:07:44,280
TO START SAMPLING, NAISAL

1764
01:07:44,280 --> 01:07:45,400
TISSUES AND SO I'M HOPING

1765
01:07:45,400 --> 01:07:47,720
THERE'S MORE AND MORE DATA THAT

1766
01:07:47,720 --> 01:07:50,080
GET ACCUMULATED FOR EVEN WITH

1767
01:07:50,080 --> 01:07:51,600
THE KINETICS OF RESPONSES LOOK

1768
01:07:51,600 --> 01:07:53,440
LIKE, THAT'S HARD TO DO THOUGH,

1769
01:07:53,440 --> 01:07:53,680
RIGHT?

1770
01:07:53,680 --> 01:07:57,000
YOU HAVE TO CAPTURE PEOPLE

1771
01:07:57,000 --> 01:07:59,160
DURING ACUTE INFECTION,

1772
01:07:59,160 --> 01:08:00,000
PREFERABLY SUPER EARLY DURING

1773
01:08:00,000 --> 01:08:01,280
THE INFECTION SO YOU KNOW WHAT

1774
01:08:01,280 --> 01:08:04,880
THE BASE LINE IS BUT WE--PEOPLE

1775
01:08:04,880 --> 01:08:07,960
WOULDN'T SHOW UP UNTIL

1776
01:08:07,960 --> 01:08:08,440
SYMPTOMATIC.

1777
01:08:08,440 --> 01:08:10,200
SO THOSE ARE REALLY IMPORTANT

1778
01:08:10,200 --> 01:08:13,400
QUESTIONS FOR US TO BED

1779
01:08:13,400 --> 01:08:16,160
UNDERSTAND WHAT MECHANISMS OF

1780
01:08:16,160 --> 01:08:18,760
PROTECTIVE IMMUNITY REALLY OCCUR

1781
01:08:18,760 --> 01:08:19,920
IN THESE TISSUES BECAUSE I DO

1782
01:08:19,920 --> 01:08:23,720
THINK IT'S QUITE HARD TO

1783
01:08:23,720 --> 01:08:26,560
EXTRAPOLATE FROM ANIMAL MODELS,

1784
01:08:26,560 --> 01:08:28,280
ANIMAL MODELS ARE AWESOME BUT

1785
01:08:28,280 --> 01:08:31,520
YOU NEED SOME DIRECT EVIDENCE IN

1786
01:08:31,520 --> 01:08:33,560
PEOPLE.

1787
01:08:33,560 --> 01:08:35,560
I REALLY--I DO--I AM QUITE

1788
01:08:35,560 --> 01:08:37,840
IMPRESSED BY THE HUMAN CHALLENGE

1789
01:08:37,840 --> 01:08:41,120
MODELS BOTH FOR SARS-COV-2 AND

1790
01:08:41,120 --> 01:08:43,000
FLU, FOR EXAMPLE IN HUMAN

1791
01:08:43,000 --> 01:08:45,080
CHALLENGE MODELS IN FLU,

1792
01:08:45,080 --> 01:08:46,720
INFECTED PEOPLE, PEOPLE WHO GOT

1793
01:08:46,720 --> 01:08:48,520
INFECTED PEOPLE WHO HAD CD8

1794
01:08:48,520 --> 01:08:51,200
T-CELLS IN THEIR LUNG, THAT'S

1795
01:08:51,200 --> 01:08:53,120
WHAT CORRELATED WITH LOWER

1796
01:08:53,120 --> 01:08:54,200
OVERALL VIRAL LOAD DURING YOU

1797
01:08:54,200 --> 01:08:56,440
KNOW WHEN THEY GOT CHECKED FOR

1798
01:08:56,440 --> 01:08:58,080
VIRAL LOAD OVER 7 DAYS AND I

1799
01:08:58,080 --> 01:09:00,040
JUST DON'T THINK YOU CAN FIND

1800
01:09:00,040 --> 01:09:01,800
THOSE THINGS UNLESS YOU GET

1801
01:09:01,800 --> 01:09:03,440
TISSUE SAMPLES WHERE YOU FIND

1802
01:09:03,440 --> 01:09:06,800
[INDISCERNIBLE] HAD IS A HIGH

1803
01:09:06,800 --> 01:09:07,360
BAR.

1804
01:09:07,360 --> 01:09:08,960
IT'S ACTUALLY AMAZING, WHAT THE

1805
01:09:08,960 --> 01:09:15,080
STUDIES ARE BEING DONE NOWADAYS.

1806
01:09:15,080 --> 01:09:16,600
SO 1 PERSON WANTED TO ASK YOU TO

1807
01:09:16,600 --> 01:09:19,600
SPEAK TO THE IDEA OF THE

1808
01:09:19,600 --> 01:09:20,960
ORIGINAL ANTIGENIC SIN AND HOW

1809
01:09:20,960 --> 01:09:22,480
COVID AND COVID VACCINES HAVE

1810
01:09:22,480 --> 01:09:24,160
CAUSED THE FIELD TO UPDATE OR

1811
01:09:24,160 --> 01:09:34,640
MODIFY THIS IDEA IF AT ALL. 

1812
01:09:36,400 --> 01:09:37,560
>>YEAH, WE DON'T--SO WE
HAVE A

1813
01:09:37,560 --> 01:09:39,680
STRONG INTEREST IN THAT TOPIC,

1814
01:09:39,680 --> 01:09:41,120
WELL FIRST AS HUMAN BEINGS WE

1815
01:09:41,120 --> 01:09:42,480
WANT TO BE PROTECTED AGAINST

1816
01:09:42,480 --> 01:09:43,760
COVID BUT WE HAVE A STRONG

1817
01:09:43,760 --> 01:09:45,320
INTEREST IN THE TOPIC IN THE

1818
01:09:45,320 --> 01:09:47,280
CONTEXT OF HIV VACCINES AND SORT

1819
01:09:47,280 --> 01:09:51,400
OF TRYING TO EXTEND UPON WHAT I

1820
01:09:51,400 --> 01:09:54,200
TALKED ABOUT TODAY WHERE TO

1821
01:09:54,200 --> 01:09:55,680
GENERATE BROADLY NEUTRALIZING

1822
01:09:55,680 --> 01:09:57,920
ANTIBODIES WE HAVE A SHEPHERDING

1823
01:09:57,920 --> 01:09:58,960
APPROACH AND THEN YOU'RE COMING

1824
01:09:58,960 --> 01:10:01,800
BACK WITH A RELATED BUT

1825
01:10:01,800 --> 01:10:02,880
DIFFERENT IMMUNO GENERATED AND

1826
01:10:02,880 --> 01:10:04,760
THEN ANOTHER DIFFERENT BUT

1827
01:10:04,760 --> 01:10:05,920
RELATED IMMUNOGEN SO YOU HAVE TO

1828
01:10:05,920 --> 01:10:08,120
HAVE A RECALL RESPONSE THAT YOU

1829
01:10:08,120 --> 01:10:12,440
CAN BUILD UPON AND HOW DO THINGS

1830
01:10:12,440 --> 01:10:16,040
LIKE IMPRINTING OR CLINICAL

1831
01:10:16,040 --> 01:10:16,920
GENETICSINAL [INDISCERNIBLE]

1832
01:10:16,920 --> 01:10:17,640
IMPACT THAT.

1833
01:10:17,640 --> 01:10:19,480
I THINK LIKE MOST OF THE FIELD,

1834
01:10:19,480 --> 01:10:24,000
I TRIED TO MOVE AWAY FROM THE

1835
01:10:24,000 --> 01:10:25,240
TERM ORIGINAL [INDISCERNIBLE]

1836
01:10:25,240 --> 01:10:27,400
BECAUSE IT INVOKES QUITE A

1837
01:10:27,400 --> 01:10:28,200
VARIETY OF EMOTIONAL RESPONSES

1838
01:10:28,200 --> 01:10:29,800
FROM PEOPLE AND I THINK

1839
01:10:29,800 --> 01:10:32,640
IMPLINTING IS A LITTLE MORE

1840
01:10:32,640 --> 01:10:32,920
NEUTRAL.

1841
01:10:32,920 --> 01:10:34,120
I CAN JUST COMMENT ON THE STATE

1842
01:10:34,120 --> 01:10:40,880
OF THE LITERATURE WHICH IS THERE

1843
01:10:40,880 --> 01:10:43,280
ARE BEAUTIFUL PREPRINTS FROM

1844
01:10:43,280 --> 01:10:47,080
LAURA WALKER AND [INDISCERNIBLE]

1845
01:10:47,080 --> 01:10:52,080
BETTY SHOWING THAT WHEN A PERSON

1846
01:10:52,080 --> 01:10:55,520
SEES OMICRON OR ANOTHER FAIRLY

1847
01:10:55,520 --> 01:10:56,240
DIVERGENT VARIANT, ALMOST ALL

1848
01:10:56,240 --> 01:11:00,000
THE RESPONSE TO THAT IS MEMORY

1849
01:11:00,000 --> 01:11:05,760
B-CELLS TO THE ORIGINAL AND

1850
01:11:05,760 --> 01:11:08,240
WHILE EVERYBODY WAS ABLE TO

1851
01:11:08,240 --> 01:11:10,040
DETECT NAIVE B-CELLS, THEY WERE

1852
01:11:10,040 --> 01:11:11,320
LESS THAN 1 PERCENT OF THE

1853
01:11:11,320 --> 01:11:17,520
RESPONSE AND SO THERE IS A VERY

1854
01:11:17,520 --> 01:11:17,920
STRONG IMPRINTING.

1855
01:11:17,920 --> 01:11:18,720
NOW I THINK IT'S EASY TO

1856
01:11:18,720 --> 01:11:20,720
ELECTRIC AT THAT AS A PRETTY

1857
01:11:20,720 --> 01:11:21,560
POSITIVE THING.

1858
01:11:21,560 --> 01:11:23,880
THIS IS ESSENTIALLY WHAT I WAS

1859
01:11:23,880 --> 01:11:25,440
TALKING ABOUT EARLIER OF IN THE

1860
01:11:25,440 --> 01:11:26,280
GERMINAL CENTER RESPONSE IS,

1861
01:11:26,280 --> 01:11:29,040
PART OF A GOAL OF THAT PROCESS

1862
01:11:29,040 --> 01:11:32,080
IS TO GENERATE MEMORY B-CELLS,

1863
01:11:32,080 --> 01:11:34,040
THAT HAVE DIVERSE RECOGNITION

1864
01:11:34,040 --> 01:11:37,240
CAPACITY AND DON'T NECESSARILY

1865
01:11:37,240 --> 01:11:38,240
RECOGNIZE THE CURRENT ANTIGEN

1866
01:11:38,240 --> 01:11:41,360
THE BEST BUT MIGHT RECOGNIZE A

1867
01:11:41,360 --> 01:11:44,360
RELATED ANTIGEN I. E. OMICRON

1868
01:11:44,360 --> 01:11:48,480
MUCH BETTER THAN WHAT I NAIVE

1869
01:11:48,480 --> 01:11:49,720
B-CELL COULD STARTING FROM

1870
01:11:49,720 --> 01:11:52,520
SCRATCH SO THERE MIGHT BE

1871
01:11:52,520 --> 01:11:53,880
MUTATIONS ON OMICRON THAT ARE

1872
01:11:53,880 --> 01:11:56,000
AFFECTING AN EPITOPE BUT IF HAVE

1873
01:11:56,000 --> 01:11:57,520
A B-CELL IT'S BINDING NOT JUST

1874
01:11:57,520 --> 01:11:59,280
TO THE BINDING OF THE CENTER OF

1875
01:11:59,280 --> 01:12:01,920
THE EPITOPE BUT BESIDE THE CELL,

1876
01:12:01,920 --> 01:12:02,920
THE B-CELL CAN STILL HANG ON AND

1877
01:12:02,920 --> 01:12:04,560
BE A GOOD RESPONDER TO THAT AND

1878
01:12:04,560 --> 01:12:07,080
I THINK THAT'S WHAT REALLY THE

1879
01:12:07,080 --> 01:12:09,000
FLU FIELD SEES IN A LOT OF ITS

1880
01:12:09,000 --> 01:12:11,200
LITERATURE HAS JUST BEEN MORE

1881
01:12:11,200 --> 01:12:12,880
DIFFICULT TO INTERPRET THE FLU

1882
01:12:12,880 --> 01:12:14,640
LITERATURE BECAUSE PEOPLE HAVE

1883
01:12:14,640 --> 01:12:16,280
SUCH INTENSE COMPLEX HISTORIES

1884
01:12:16,280 --> 01:12:17,000
WITH FLU.

1885
01:12:17,000 --> 01:12:18,720
YEAH, I GUESS I WILL STOP THERE.

1886
01:12:18,720 --> 01:12:20,520
THOSE ARE MY MAIN THOUGHTS.

1887
01:12:20,520 --> 01:12:21,680
>>YEAH, I THINK WE'RE
GOING TO

1888
01:12:21,680 --> 01:12:23,920
HAVE TO STOP BECAUSE OF THE

1889
01:12:23,920 --> 01:12:25,280
TIME.

1890
01:12:25,280 --> 01:12:25,600
>>COOL.

1891
01:12:25,600 --> 01:12:30,360
>>THIS IS REALLY
WONDERFUL AND

1892
01:12:30,360 --> 01:12:31,440
YEAH, WE ARE--YOUR COMMENTS ON

1893
01:12:31,440 --> 01:12:33,560
THE FLU AND THE HISTORY, IT DOES

1894
01:12:33,560 --> 01:12:37,640
BRING HOME HOW WE ARE LIVING IN

1895
01:12:37,640 --> 01:12:38,480
THE WORLD'S BASED EXPERIMENT AND

1896
01:12:38,480 --> 01:12:42,840
WE ARE THE SUBJECTS.

1897
01:12:42,840 --> 01:12:44,920
AND I THANK YOU FOR PROVIDING

1898
01:12:44,920 --> 01:12:45,800
YOUR INSIGHT, SO, THANKS

1899
01:12:45,800 --> 01:12:46,440
EVERYONE AND WE WILL SEE YOU IN

1900
01:12:46,440 --> 01:12:47,400
2 WEEKS.

1901
01:12:47,400 --> 01:12:48,680
>>YEAH, THANKS IF YOUR
TIME AND

1902
01:12:48,680 --> 00:00:00,000
ALL THOSE EXCELLENT QUESTIONS.