WELCOME TO A REALLY UNIQUE WEDNESDAY TWELVE NOON LECTURE. THE ANNUAL POSSIBILITY TO SPEAK WITH An IDENTIFIED SCIENTIST WORKING IN AREAS OF IMMUNOLOGY WHICH WERE THE UNBELIEVABLE PAYMENTS OF OUR LONG TERM NIH SCIENTIFIC LEADER BILL PAUL WHO WAS CHIEF OF THE NIAID LAB OF IMMUNOLOGY. IT'' S QUITE A WEEK WE ' RE HAVING RIGHT HERE WITH NOBELS BEING REVEALED THIS WEEK. I TIN SAY FOR ONE MOMENT, HOW PLEASED WE WERE ALL MONDAY MORNING AT 5:30 A.M.TO LEARN ONE OF OUR OWN SCIENTISTS, HARVEY ALTER WAS AMONGST THOSE CHOSEN FOR THE NOBEL PRIDE IN MEDICATION AND PHYSIOLOGY FOR THE WORK HE DID ON HEPATITIS C WITH 2 OTHER ASSOCIATES. WE HAD A WONDERFUL DAY WITH HARVEY ON MONDAY PHYSICALLY DISTANCED APPROPRIATELY BUT HOLDING An INTERVIEW AND ALSO SOCIAL MEDIA ACTIVITIES AND ALSO REMINDING OURSELVES OF WHAT A WONDERFULLY GENTLE SELF-EFFACING MAN WHO JUST INTENDED TO HELP PEOPLE AVOID A HORRIBLE DISEASE. CONGRATS TO HARVEY AS WELL AS ONCE AGAIN TODAY DISCOVERING AFTER SOME ANTICIPATION OVER THE LAST 3 OR 4 YEARS THE NOBEL COMMITTEE DECIDED IT WAS TIME FOR CRISPR KAS TO BE RECOGNIZED THAT ALTERED EVERY LITTLE THING IN MOLECULAR BIOLOGY AND ALSO AWARDED TO TWO WOMEN MAKING IT EVEN MORE REMARKABLE BOTH EXTREMELY DESERVING OF THE RECOGNITION. IT'' S WONDERFUL TO HAVE SOME REALLY GOOD WONDERFUL THINGS OCCURRING IN THE MIDST OF WHAT IS ADMITTEDLY A CHALLENGING YEAR. WE'' RE DOING IT VIRTUALLY AND ALSO MORE PEOPLE HAVE THE ABILITY TO WEB LINK IN AND ALSO CAPITALIZE ON THE SCIENCE WE'' RE ABOUT TO SPEAK WITH OUR AUDIO SPEAKER. BEFORE I GET TO INTRODUCE THE AUDIO SPEAKER THOUGH I WANT TO SAY SOMETHING ABOUT EXPENSE PAUL BECAUSE SEVERAL OF THE MORE RECENT ARRIVALS AT THE NIH MIGHT NOT KNOW ABOUT THIS LEGENDARY CHARACTER.HE WAS A SHINING SYMBOL AND INTERNATIONAL GIANT IN CONTEMPORARY IMMUNOLOGY. HE HAD AN SUBSTANTIAL EFFECT ON SCIENCE AS WELL AS BEING An INSTRUCTOR OF LOTS DISTINGUISHED LEADERS WHO HAVE GONE ON TO COME TO BE QUITE FAMOUS THEMSELVES IN THE FIELD AND MOST OF WHOM ARE THEMSELVES NOW ASSOCIATED WITH TRYING TO UNRAVEL THE IMMUNOLOGICAL ENIGMAS OF THE COVID-19 PANDEMIC. I ' M LIKEWISE DELIGHTED TO SAY AMONGST THE FOLKS SIGNING UP WITH US REMOTELY, IS EXPENSE ' S WIDOW, MARILYN. IT ' S WONDERFUL YOU CAN SIGN UP WITH THE GATHERING. I'' M EVER JOYED RECALLING AT YOUR MEMORIES OF EXPENSE WHILE I WAS PREPARING TO PERFORM THE INTRO AS WELL AS FOUND EYE COLLECTION OF FEEDBACK– A SET OF FEEDBACK YOU PLACE IN THE FRONTIERS OF IMMUNOLOGY CONTRIBUTE TO BILL AN WHOLE UNIQUE ISSUE AS WELL AS YOU CLAIMED AND ALSO I ' M QUOTING EVERYDAY HE WENT TO WORK WAS A JOYOUS DAY.EVERY EVENING HE FUNCTIONED AT RESIDENCE WAS A CHEERFUL EVENING. AT THE END OF THE DAY HE STATED HE ' D QUIT ONLY WHEN HE REALIZED HE HAD TO READ SOMETHING THREE TIMES. HE TOOK THAT AS A SIGNAL HE WAS TIRED AND ALSO NEED TO STOP AND HAVE SOME ICE LOTION. WELL SHOULD HAVE GELATO. I ' M GOING REMEMBER THAT THE NEXT TIME I UNDERSTAND I NEEDED TO READ SOMETHING 3 TIMES SINCE IT DOES HAPPEN. WHAT A WONDERFUL METHOD TO ASSESS COSTS AS WELL AS FOR THOSE THAT RECOGNIZED HIM, HE RADIATED THAT HAPPINESS AND ALSO THE EXPERIENCE OF DOING SCIENCE AND ALSO LEARNING POINTS REGARDING THE BODY IMMUNE SYSTEM. AND MARILYN IF YOU ' RE ABLE TO UNMUTE AND ALSO SAY A WORD TO THE PUT TOGETHER TEAM IT WOULD BE TERRIFIC TO LISTEN TO YOUR VOICE FOR A MINUTE. ARE YOU'THERE? > > THANK YOU FOR THE OPPORTUNITY? AS WELL AS FOR PERFORMING THE LECTURE THOUGH IT NEEDS TO BE DIGITAL, I ' M SURE COSTS WOULD >> HAVE ACCEPTED OF THAT DECISION.NOW I HAVE A LITTLE SENTENCE I ' D LIKE TO ADD. I WISH IT ' S NOT TOO EMBARRASSING BUT I HAVE REMARKABLE MEMORIES OF THE TIME
WE WERE LIVING IN NEW YORK CITY AS WELL AS COSTS AS WELL AS I AND RUTH AND VICTOR WOULD SPEND SOCIAL TIME AND SCIENCE TIME TOGETHER. THOSE WERE REMARKABLE YEARS. AFTER THAT I HAVE ANOTHER MEMORY I ' D LIKE TO SHARE OF MICHELLE AND ALSO MY CHILD MATTHEW HAVING FUN BASKETBALL AT A GORDON MEETING AND THESE 2 TEEN AGE CHILDREN WERE HAVING A GREAT DEAL OF ENJOYABLE WHILE THEIR PARENTS WERE DOING SCIENTIFIC RESEARCH AND THIS IS A VERY LONG TIME AGO. WAY prior to iPHONES as well as CAMERAS SO I DON ' T HAVE A PICTURE TO SHARE. BUT I DO HAVE THAT LOVELY IMAGE ETCHED IN MY OWN MIND. THANKS FOR PERMITTING ME TO SHARE THAT AND THANK YOU AS WELL AS CONGRATULATIONS ON MICHELLE HONORING COSTS THIS AFTERNOON. > > MANY THANKS FOR THAT WONDERFUL REFLECTION. I DIDN ' T FIND OUT ABOUT THOSE LINKS. I ' M GLAD YOU WERE ABLE TO >> SHARE THEM. I UNDERSTAND WE ' RE 550 INDIVIDUALS ARE SEEING AND ALSO THE NUMBER IS STILL GROWING.BUT IT ' S TIME FOR KNOW INTRODUCE THE ACTUAL SPEAKER. MICHEL NUSSENZWEIG OF ROCKEFELLER UNIVERSITY. POSSIBLY AFTER WHAT WE ' VE BEEN THROUGH THIS YEAR WE CANISTER ALL USE A BIG BOWL OF GELATO AND THIS IS OUR INTELLECTUAL VERSION OF THAT BECAUSE MICHEL THAT IS A COLLEGE STUDENT, WAS ABLE TO IDENTIFY THE DENDRITIC CELLS AND ALSO NOW INCREASING TO THE DIFFICULTY OF COVID-19 WHICH IS WHAT HE ' S GOING TO TALK TO United States ABOUT TODAY, USING A MIX OF BIOCHEMISTRY AND BIOLOGY AS WELL AS MOLECULAR GENETICS AS A HAZE– ROCKEFELLER TEACHER HAS PIONEERED IN ANTIBODY BASED THERAPIES FOR HIV AS WELL AS HIS TREND IS FAD IS FOCUS TO WHAT MAY BE DONE FOR SARS COV2 A TOPIC THAT COULDN ' T BE EVEN MORE TIMELY.THIS MORNING THE LILLY FIRM LAUNCHED INFORMATION THEY FEEL THEY HAVE ENOUGH PRELIMINARY DATA ABOUT A MONOCLONAL ANTIBODY DIRECTED VERSUS SARS COV2 THEY INTEND TO HEAD TO FDA AND ALSO REQUEST EMERGENCY USE CONSENT. THIS IS STARTING TO FUNCTION. I WISH TO LISTEN TO FROM MICHEL ABOUT THE ABCS AND HOW WE BRING IT AHEAD TO THE INTERNATIONAL PANDEMIC. WITHOUT FURTHER ADO LET ME ASK YOU PRACTICALLY TO WELCOME OUR AUDIO SPEAKER FOR THE WILLIAM WALL LECTURE THE HUMAN ANTIBODY ACTIONS TO SARS COV2. > > THANKS, FRANCIS. THANKS, MARILYN. IT ' S REALLY SUCH AN HONOR TO ACCOMPLISH THIS. AS MARILYN MENTIONED MY PARENTS AS WELL AS BILL AND ALSO MARILYN WERE CLOSE AT THE ALL TIME THEY WERE WORKING AT NYU AND ALSO A GOT TO MEET >> EXPENSE BACK THEN AS WELL AS EVENTUALLY WHEN I ENDED UP BEING A SCIENTIST, EXPENSE WAS EXCEPTIONALLY HELPFUL IN MANY WAYS AS WELL AS I OBTAINED INTERACT WITH HIM AT NIH AT THE HOWARD HUGHES AND A BUNCH OF MEETING WHERE BILL WOULD OCCASIONALLY TAKE KNOW DINNER WITH MARILYN SO IT ' S A FANTASTIC HONOR TO DO THIS FOR BILL.WHAT I ' LL SPEAK ABOUT TODAY, FIRST, OF IMMUNOLOGY WHICH PERTAINS TO UNDERSTANDING HOW INDIVIDUALS REACT TO THE CORONAVIRUS. SOMETHING ABOUT HOW WE CAME TO FUNCTION ON THE CORONAVIRUS AND THE EXPERIMENTS. THIS SLIDE REVEALS YOU WHAT I ' M GOING TO SPEAK ABOUT TODAY SO NOT SIMPLY THE FUNCTION OF ONE LAB BUT THE FUNCTION OF DIFFERENT LABS AND ALSO SUPPORTED COMPLETELY OR IN HUGE PART BY THE NIH.AND I OUGHT TO SAY THAT THAT ASSISTANCE ORIGINATES FROM THE EXTREMELY LEADING AND ALSO LOTS OF COWORKERS AT NIH AS WELL AS I SHOUT-OUT TO MANY THAT HAVE BEEN INVOLVED IN CREATING AS WELL AS AIDING PERFORM SEVERAL OF THE EXPERIMENTS THE ANIMAL EXPERIMENTS THAT I ' M GOING TO SPEAK ABOUT AT THE END OF THE
TALK. SO WITH THAT, LET ' S START. SO FIRST THING IS WHAT MY LAB HAS BEEN CURIOUS ABOUT FOR A LONG TIME IS THIS PROBLEM THAT OFHERM HERMAN EISEN DISCOVERED IS THERE ' S RHYTHMIC BOOST IN THE AFFINITY'OF ANTIBODIES AFTER INFECTION. WE DISCOVERED A GREAT DEAL ABOUT HOW THIS OCCURRED. HIGHLIGHTED PARTIALLY ON THIS SLIDE. SO THE IMMUNE SYSTEM OF COMPOSED OF CELLS. EACH CELL HAS An ONE-OF-A-KIND RECEPTOR WITH A SPECIFICITY AS WELL AS
WHEN THE IMMUNE SYSTEM IS CHALLENGED BY An INFECTION OR SOME VIRUS, CELLS THAT HAVE THE PROPER RECEPTORS ARE EXPANDED.WHAT HAPPENS IN THE B CELL AREA IS THEY DON ' T JUST UNDER GO CLONAL DEVELOPMENT THEY ALSO DIVERSIFY THEIR ANTIBODY GENETICS THROUGHOUT CLONAL GROWTH. THIS IS REALLY A STRANGE POINT AS WELL AS THEY DO IT BY MUTATIONS SOMATIC ANOMALY SO THE ENZYME AID DISCOVERED BY COLLEAGUES AND ALSO ANOTHER TEAM IN FRANCE AT THE SAME TIME ENTERS INTO THE GENOME AND ALSO MAKES SMALL MUTATIONS IN ANTIBODY GENES AS WELL AS AS OPPOSED TO A MONOMORPHIC NONO CLONAL DEVELOPMENT YOU GET LIMB POE ENEMY SIGHT DIFFER– LYMPHOCYTES AND THERE ' S An OPTION FOR CELLS CREATING HIGH ANTIBODIES WHICH IS HOW YOU GET THE AFFINITY GROWTH DISCOVERY BY EISEN AND YOU OBTAIN An INEQUALITY IN DNA AND THAT INEQUALITY IS AFTER THAT PROFESSORED TO DEVELOP SOMATIC– REFINED TO TO PRODUCE SOMATIC CONVERSIONS AND IT ' S DANGEROUS BECAUSE IT CANISTER CAUSE CHROMOSOME TRANS PLACE OR ANOMALIES THAT ARE CANCER PRODUCING AND ALSO ACTUALLY A LOT OF THE LYMPHOMAS IN HUMAN BEINGS COME AS A RESULTS OF THIS ANOMALY AND ALSO AS A MATTER OF FACT THIS IS CRITICAL.AND HERE ' S IN THESE EXAMPLES FROM HIV. THESE ARE 4 VARIOUS HIV ANTIBODIES. YOU CAN SEE THEIR SPR TRACES AS WELL AS HAVE AN FONDNESS FOR THE ANTIGEN BUT IF YOU ELIMINATE THE MUTATIONS THAT DISAPPEARED. AND IMPORTANTLY THE ANTIBODIES ARE REDUCING THE EFFECTS OF AND ALSO IF YOU TAKE IT AWAY ALL THE COUNTERACTING ANTIBODIES VANISHES THIS PARTICULAR
REACTION'HAPPENS IN UNIQUE STRUCTURES THAT ARE IN UTILIZED ORGANS CALLED GERMINAL FACILITIES A DARK AND ALSO LIGHT ZONE. AND ALSO WHAT MY COLLEAGUES AND I HAVE DONE OVER THE LAST SEVERAL YEARS IS DEVELOP A DESIGN TO SHOT TO EXPLAIN HOW THE OPTION PROCEDURE OPERATES IN THE GERMINAL CENTERS.WHAT WE FOUND AND ALSO THIS IS THE WORK OF MANY LABS AND WE HAVE ADDED CONSIDERABLY TO THIS IS THE DARK ZONE THAT FIRST AREA SO WHERE THE LYMPHOCYTES ARE UNDERTAKING THE CLONAL EXPANSION AND IN WHICH THEY ' RE MUTATING. THIS STRUCTURE IS DYNAMIC AS WELL AS CELLS RELOCATE FROM ONE ZONE TO ANOTHER PERSON AND ALSO AN ORCHESTRATED SET OF ACTIVITIES WHEN THEY FINISH MOVING THEY GO TO
THE LIGHT ZONE AND ALSO THE LIGHT AREA WHERE THE PINK STUFF REMAINED IN THE PREVIOUS SLIDE IS WHERE THE CELLS WITH BRAND-NEW RECEPTORS THAT HAVE BEEN MUTATED TEST THEIR RECEPTORS ON THE INTI GEN. THEY TEST WEATHHETHER OR OTHERWISE THEY CONTAINER STILL POINT AND ALSO COMPETE FOR BINDING TO THE ANTIGEN. THE CELLS WITH ONE OF THE MOST ANTIGEN CANISTER EXISTING THAT TO CELLS THAT STAY IN THE LIGHT ZONE AND ALSO ONLY THE CELLS THAT HAVE THE FINEST RECEPTORS ARE SELECTED BY THE T CELLS ON THE BASIS OF JUST HOW MUCH ANTIGEN THEY PICKED UP AND GO BACK DOWN AND DIVIDE ONCE MORE AS WELL AS ALTER AGAIN AS WELL AS GO BACK DOWN AND RETURN UP AGAIN AND ALSO REPEAT THE CYCLE.YOU CAN VISUALIZE HOW THAT WOULD QUICKLY CAUSED THE CHOICE OF CELLS WITH HIGH FONDNESS RECEPTORS. CURRENTLY, THERE ARE TWO PRODUCTS OF THIS REACTION AND ALSO BOTH PRODUCTS OF THE RESPONSE ARE MEMORY B CELLS AND PLASMA CELLS. AND ALSO THEY ' RE REALLY VERY VARIOUS CELL TYPES. THE PLASMA CELL IS MAKING THE ANTIBODIES WE ' RE SEARCHING FOR IN OUR PLASMA BEING USED IN THE
CORONAVIRUS INFECTION. AND ALSO THE MEMORY CELLS IS A TANK, SOMETHING AHEAD BACK TO. INDIVIDUALS RESEARCHED PLASMA CELLS QUITE A BIT AND ALSO IT ' S CLEAR THEY ' RE SELECT FROM THIS ENVIRONMENT FROM THE GERMINAL CENTER SETTING BASED BUNCH THE AFFINITY.HIGH AFFINITY B CELLS OBTAIN CHANGED TO ANTIBODIES. LESS IS KNOWN ABOUT THE MEMORY CELL. AS WELL AS IT ' S BEEN RESEARCHED PRIMARILY BY CAPTURING IT UTILIZING ANTIGENS. SO THAT CALLS FOR THAT CELL HAVE A CERTAIN FONDNESS IN ORDER TO BE SEEN. WHAT I ' LL SPEAK ABOUT IN THE NEXT FEW SLIDES IS THE FUNCTION OF A POST-D POST-DOCTORAL IN THE LABORATORY WHO DETERMINED TO LOCATE OUT MORE ABOUT MEMORY CELLS NOT BY THEIR
CAPACITY TO BIND ANTIGEN BUT BY LINEAGE TRACING AND SHE DID THIS BY LABELLING CELLS THAT ARE GOING INTO THE GERMINAL CENTER SO ONCE THEY ' RE LABELLED THEY STAY LABELLED AND ALSO THE PRODUCTS ARE LABELLED. AND SHE DID THIS WITH A TAMOXIFEN INDUCIBLE CREAM. AS WELL AS WHAT IS THE MEMORY OF B CELLS IF WE TAKE ALL COMERS AND ALSO CONTRAST THEM TO CELLS IN GERM INIAL CENTERS? THERE ' S AN BOOSTER SHOT AND ALSO WE TAG THEM AROUND DAY FIVE 2 OR THREE DAYS EVEN MORE AND ALSO NOW SEARCH IN THAT GERMINAL FACILITY OR IN MEMORY CELLS 42 DAYS LATER FOR ANTIGEN BINDING.AND WHAT YOU CAN SEE RIGHT HERE IS THAT IT ' S EASY TO FIND CELLS THAT BIND TO THE ANTIGEN IN THE GERMIN SIGNAL FACILITY. THAT ' S EXPECTED BUT BUT IN THE MEMORY COMPARTMENT AS THE FEW CELLS WITH ADEQUATE AFFINITY TOA SIGNAL CENTER. THAT ' S EXPECTED BUT BUT IN THE MEMORY COMPARTMENT AS MINORITY CELLS WITH ENOUGH FONDNESS TOL SIGNAL FACILITY. THAT ' S EXPECTED BUT BUT IN THE MEMORY AREA AS THE FEW CELLS WITH ENOUGH FONDNESS TOIGNAL CENTER. THAT ' S ANTICIPATED BUT BUT IN THE MEMORY COMPARTMENT AS MINORITY CELLS WITH ENOUGH FONDNESS GNAL FACILITY. THAT'' S EXPECTED BUT BUT IN THE MEMORY AREA AS MINORITY CELLS WITH SUFFICIENT AFFINITY TONAL FACILITY. THAT'' S ANTICIPATED BUT BUT IN THE MEMORY COMPARTMENT AS MINORITY CELLS WITH SUFFICIENT AFFINITY AL FACILITY. THAT'' S EXPECTED BUT BUT IN THE MEMORY COMPARTMENT AS THE FEW CELLS WITH ADEQUATE FONDNESS L FACILITY. THAT'' S EXPECTED BUT BUT IN THE MEMORY COMPARTMENT AS THE FEW CELLS WITH ENOUGH AFFINITY TO CENTER. THAT'' S ANTICIPATED BUT BUT IN THE MEMORY AREA AS THE FEW CELLS WITH ADEQUATE AFFINITY TO BE SEEN BY THE ANTIGEN AND ALSO THAT ' S SHOWN IN MULTIPLE EXPERIMENTS ON THE RIGHT.NOW, THIS IS REAL THROUGHOUT THE IMMUNE FEEDBACK. SO YOU TIN SEE RIGHT HERE IF WE LABEL FROM DAY 9 OR DAY 15 IF WE TAG FROM DAY 21, IT ' S CONSTANTLY THE SAME. THERE ARE CELLS IN THE GERMINAL CENTER WITH RARE FONDNESS BUT RARE IN THE MEMORY AREA. ALL RIGHT, SO DOES THAT MEAN THAT MEMORY CELLS WEAR ' T HAVE ANY AFFINITY FOR THE ANTIGEN? NO. THAT ' S NOT THE CASE. WHAT WE DID TO TRY TO UNDERSTAND THIS WAS TO CLONE THE ANTIBODIES
FROM CELLS TAGS CELLS AT THE VERY SAME TIME AS WELL AS TO BIND WITH AN ANTIGEN ON A CHIP. THIS IS WHAT THE CIRCULATION CYTOMETRY RESEMBLES AND THERE ' S CELLS WITH AFFINITY IN THE GERMINAL FACILITY BUT HARD TO DISCOVER ONE IN THIS INSTANCE OUT OF 41 THAT HAVE THE DEMONSTRABLE MONOVEIL ENT– MONOVALENT FONDNESS BUT IT ' S ON THE FOLLICULAR DENDRITIC CELLS AND ALSO THOSE ARE POLYMERS SO SHOT WITH A POLY VALENT SITUATION.AND A FEW EVEN MORE OF THE ONES WE COULDN ' T FIND IN THE GERMINAL FACILITY ALSO COME UP. WE CANISTER FURTHER INCREASE THE SO-CALLED LA VIDITY OF THE ASSAY BY MAKE TETTRIMER AND ALSO YOU SEE MORE OF THE MEMORY CELLS HAVE SOME FONDNESS.'SO THE MEMORY CELLS ARE CAN BE FOUND IN THAT COMPARTMENT WITH ACTUALLY REALLY LOW LEVELS OF FONDNESS. THERE ARE CELLS SUCH AS THIS ONE BELOW WITH FAIRLY HIGHER FONDNESS AS WELL AS BY'AND ALSO LARGE THE CELLS ARE VARIATIONS THAT HAVE REDUCED FONDNESS FOR THE ANTIGEN. FOR PLASMA CELLS THE OPTION IS CLEAR IT
' S BASED ON AFFINITY.FOR MEMORY CELLS,'WHO YOU OBTAIN IS An ENTIRE COLLECTION OF LYMPHOCYTES AS WELL AS IT MAY BE A METHOD FOR THE BODY IMMUNE SYSTEM TO LOOK ONWARD TO VARIANTS OF THE VIRUS. SO THE MICROORGANISM IS GOING TO DEVELOP AND ALSO THE IMMUNE SYSTEM IS CREA CREATING A MEANS OF MANAGING THAT DEVELOPMENT. CURRENTLY I INTEND TO TELL YOU A LITTLE ABOUT HOW WE GOT TO CORONAVIRUS IN 2 OR 3 SLIDES. SO WHAT WE STARTED TO FUNCTION ON WAS HIV SINCE IT WAS AND ALSO IS A SIGNIFICANT PUBLIC WELLNESS PROBLEM. AND EXTREMELY LITTLE UNDERSTANDING OF WHY WE DON ' T REALLY HAVE An EXCELLENT INJECTION
. IT WAS KNOWN AS THERE WERE INDIVIDUALS OCCASION INDIVIDUALS THAT WOULD BE ABLE TO PRODUCE SEROLOGIC ACTIVITY ANTIBODIES THAT HAD THE ABILITY TO NEUTRALIZE THE INFECTIONS AND IF YOU HAD THE ABILITY TO REPRODUCE THAT, AFTER THAT YOU CAN PRODUCE A VACCINE BUT THESE PEOPLE WERE UNUSUAL. THEIR IMMUNE ACTION IS UNUSUAL BECAUSE IT DEVELOPED AFTER TWO FOR 3 YEARS NOT LIKE THE SLIDE AT THE BEGINNING IN WHICH YOU GET HIGH FONDNESS RIGHT AWAY.THIS SAY PROCEDURE THAT TOOK YEARS– IS A PROCESS THAT TOOK YEARS TO TAKE PLACE AND WERE INTERESTED TO SEARCHING FOR OUT WHAT ARE THESE PEOPLE, WHAT ARE THEY DOING AND ALSO HOW DID THEY DO THIS? WE BEGAN THE TRY OUTS A GREAT DEAL OF AID FROM THE CONTAINER– VRC TO RECRUIT INDIVIDUALS AS WELL AS DEVELOPED THE EXACT SAME INNOVATION THAT ' S BEEN UTILIZED BY PRACTICALLY EVERYBODY TOWEL ANTIBODIES FROM PEOPLE– CLONING ANTIBODIES FROM HUMAN FROM THAT TIME ON. THAT IS TO SELECT THESE PEOPLE, TAKE OUT THEIR LYMPHOCYTES FROM THEIR BLOOD AS WELL AS INCUBATE THE LYMPHOCYTES WITH THE HEALTHY PROTEIN TARGET YOUR INTERESTED IN. WHEN IT COMES TO THE HIV IT ' S THE HIV SPIKE. WHEN IT COMES TO THE ZIKA INFECTION, IT ' S THE ZIKA VIRUS SPIKE. IN THE INSTANCE OF JUNGLE FEVER, IT ' S MALARIA ANTIGENS AS WELL AS SO ON.AND UTILIZING THE TECHNOLOGY CANISTER FIGURE OUT AND ALSO SEE THE CELL THAT BINDS AND HAS An EXCELLENT RECEPTOR THAT BINDS THE ANTIGEN TYPE THOSE AS SOLITARY CELLS AND ALSO RECREATE THE'ANTIBODIES BY MOLECULAR BIOLOGY STRATEGIES. IN HIV THIS LEDDED TO– CAUSED THE LOCATING OF POTENT ANTIBODIES B OUR GROUP AS WELL AS OTHERS THAT ADOPT THE TECHNIQUE AND THE VRC IMPROVED ON THE METHODS AS WELL AS THE ANTIBODIES HAVE NOW BEEN PROGRESSED INTO THE CENTER FOR TREATMENTS AND AVOIDANCE. AS A MATTER OF FACT WE ' LL SOON FIND OUT ABOUT A LARGE TEST FUNDED'BY NIH USING AN ANTIBODY DISCOVERED BY VRC FOR HIV AVOIDANCE. ESSENTIALLY WE HAVE BEEN LOOKING AT
EXPERIMENTS LOOKING AT HUMAN BEING ANTIBODY RESPONSES AS WELL AS WE WERE PREPARED TO PERFORM THE SAME WHEN THE CORONAVIRUS CAME UP. AND REMAINING IN NEW YORK WE WERE HIT EARLY AND DIFFICULT BY THIS ENDEMIC AND ALSO WE WERE ABLE TO RAPIDLY RECRUIT INDIVIDUALS THAT HAD RECOUPED FROM THE ILLNESS TO ROCKEFELLER COLLEGE MEDICAL FACILITY WHERE WE SCREENED 2,000 PEOPLE AND AFTER THAT ULTIMATELY RECRUITED 150 VOLUNTEERS TO COME TO THE COLLEGE TO GIVE BLOOD THAT WE COULD THEN EXAMINE IN A VARIETY OF WAYS BOTH THE PRODUCTS AND CELLS WHICH ' S THE FUNCTION I ' M GOING TELL YOU CONCERNING NOW.SO FOR THE CORONAVIRUS WE KNEW A WHOLE LOT ABOUT IT AS WELL AS IT WAS CLEAR THE SPIKE FROM THIS VIRUS ENGAGES WITH HUMAN CELLS THROUGH THIS RECEPTOR ACE 2 AND ALSO IT ' S THIS RECEPTOR BETWEEN THE RECEPTOR BINDING DOMAIN NAME WE WERE A LOT OF THINKING ABOUT BECAUSE IF ANTIBODIES COULD BLOCK THIS THEY COULD BLOCK THE INFECTION AS WELL AS IF WE COULD DISCOVER THE ANTIBODIES WE COULD LEARN SOMETHING ABOUT HOW HUMANS TAKE CARE OF THE VIRUS. SO WHAT WE DID AT FIRST WAS TO TAKE THOSE 150 SERA AND ALSO SEARCH FOR THE CAPABILITY TO BIND TO THAT REGION OF THE SPIKE.THE SO-CALLED RECEPTOR BINDING DOMAIN NAME, RBD. YOU SEE THE INFORMATION HER AND THE AREAS UNDER THE CONTOURS AS WELL AS WHAT YOU TIN SEE BELOW IS THAT THESE MANAGES ARE INDIVIDUALS PRIOR TO CORONA ESSENTIALLY AND THIS IS THE TEAM OF 148 AND THERE IS SENSITIVITY BUT IT IS NOT A HUGE QUANTITY OF SENSITIVITY. SO PEOPLE THAT HAVE RECOVERED HAVE MADE ANTIBODIES BUT NOT TREMENDOUS FIGURES TO THIS RBD. THE BINDING OF THE ANTIBODIES IS INTERESTING BUT MORE INTERESTING IS NEUTRALIZATION AND ALSO THIS WAS FUNCTION USED UP A LABORATORY YOU HEARD A BIT ABOUT RECENTLY. THEY GENERATED A PSEUDOVIRUS BY UTILIZING AN HIV BACKION– BACKBONE AND ALSO INSERTING THE SPIKE SO THE PSEUDOVIRUS HAS THE CORONA SPIKE ON IT AS WELL AS HAS A GREAT ASSAY.
SO WHAT WE DID TOGETHER WAS TO EXAMINATION THE SERA FIRST FOR NEUTRALIZING ACTIVITY AS WELL AS THE PSEUDOVIRUS ASSAY IS QUITE A GOOD ASSAY AND ASSOCIATES EFFECTIVELY WITH THE NEUTRALIZING ACTIVITY VERSUS THE ACTUAL SARS INFECTION. THAT FUNCTION WAS DONE IN CHARLIE RICE ' S LABORATORY AND YOU SEE MONOCLONAL ANTIBODIES AND ALSO STRONG ASSAYS. THIS REVEALS THE TOP 60 OF THE 148 AS WELL AS WHAT IS REMARKABLE BELOW IS THAT HALF THE INDIVIDUALS HAVE TITERS LISTED BELOW AND THE RED HAVE BELOW THIS WITH ONE WILL THIRD 1-50. SO NOT A GREAT DEAL OF NEUTRALIZING TASK IN THESE INDIVIDUALS. THE NEUTRALIZATION IN THIS INSTANCE IS HAS BIVALENT BINDING AS WELL AS WHEN YOU MAKE A YOU MAKE A FAB IT TAKES MORE OF THAT TO NEUTRALIZE THE VIRUS THAN A BIVALENT ANTIBODIES AND ALSO IT ' S BEEN CONFIRMED IN LABS ALONG WITH OTHER DATA I JUST SHOWED YOU. IF YOU ' RE ONLY HOLDING ON WITH ONE HAND AND LET GO IT MIGHT FALL AWAY. THEY ' RE LOW LEVELS OF REDUCING THE EFFECTS OF ANTIBODIES AS WELL AS EXISTING IN ALMOST ALL INFECTED INDIVIDUALS. AS WELL AS CROSS LINKING IS AN CRUCIAL MECHANISM HERE IN NEUTRALIZATION. WHAT ABOUT THE FACILITY AS WELL AS THE pWITH a few of THESE THINGS.LATE FIRST OF ALL AS WELL AS IF YOU WISHED TO PROVIDE IT COUNTERACTING AND ALSO THEY GENERALLY HAVE BETTER TITERS AND ALSO GUYS ARE BETTER TITERS THAN WOMEN.THE NEUTRALIZING TASK BECAUSE THESE ARE ALL PROBABLY CO-DEPENDENT VARIABLES. NEUTRALIZING TASK ASSOCIATES WITH THE SIGNS AND SYMPTOMS AND SIGNS INTENSITY AND AGE. THE LONGER YOU ' RE CONTAMINATED THE MORE ANTIGEN YOU HAVE AND ALSO THE BETTER IT IS FOR YOUR IMMUNE SYSTEM IN REGARDS TO BEING SUBJECTED TO ANTIGEN AS WELL AS HAVING THE ABILITY TO'GENERATE ANTIBODIES. MEN THAT ARE SICKER THAN WOMEN FIT IN TO THAT OR HOSPITALIZED PEOPLE TOO. AND ALSO THERE ' S MONOCLONAL ANTIBODIES BEING PRODUCED AND ALSO WE DID THAT THE MEANS I DISCUSSED EARLIER WHICH IS TO TAKE CELLS AND DISCOLOR THEM WITH THE ANTIGEN THE SARS COV2 SPIKE RBD AND USE THAT TO SORT CELLS AND ALSO USE MOLECULAR BIOLOGY AND THIS WAS THE BAIT, THE RBD. WE KNOW THIS THE INTERACTION. WE DON ' T SEE CELLS THAT BIND TO
THE RBD AS WELL AS CONTROL AS WELL AS THEY NECESSITY EXIST BUT THEY ARE RARE. IN ALL THE INDIVIDUALS WE CAN FIND THESE CELLS. SO DIFFERENT PEOPLE MAKE SIMILAR ANTIBODIES AND ALSO YOU TIN SEE THAT DESCRIBED HERE IN THE PLOT. AND'SOME MUCH THESE ANTIBODIES WERE VERY POTENT THAT ' S SHOWN RIGHT HERE VERSUS THE AUTHENTIC SARS COV2 IN CHARLIE RICE ' S LAB WHO ' S BEEN A CLOSE PARTNER IN THE PROJECT AS WELL AS YOU CAN SEE THE ANTIBODIES ARE NANO GRAM POTENCY AGAINST THE VIRUS.AND ONCE AGAIN THIS IS A MUCOSAL INFECTION. ANTIBODIES HAVE A COMBINATION TO GENERATE THINGS LIKE IGA AS WELL AS IGA EXISTS AS A MONOMER IN BLOOD AND ALSO AS A POLYMER AND ALSO AT THE SAME TIME THEY WERE PRODUCING IGGs THEY WERE CREATING Relevant IGAs TO SOMEWHAT EXPECTED AS WELL AS WE DID THEM FOR THREE PEOPLE AND IN EVERY INSTANCE WE CAN SEE ASSOCIATED CLONES PRESENT AS IGGs And Also IGAs. AND ALSO WHY THE MUCOSAL DISTRIBUTION INJECTIONS ARE OPERATING IN THE PET MODELS AS WELL AS NOT JUST PRESENT AS A DIMER BUT MULTIMER TO CROSS LINK THE INFECTION. POTENT ANTIBODIES IN LOTS INDIVIDUALS IN ALL PEOPLE BASICALLY. THE B CELLS PRODUCING THE B CELLS ARE RARE IN CIRCULATION AS WELL AS HAVE LOW LEVELS OF SOMATIC MUTATION AND NEARLY IDENTICAL ANTIBODIES IN DIFFERENT PEOPLE AS WELL AS SOME OVER REPRESENTATION OF PARTICULARLY THE GENETICS AS WELL AS WE ' LL GO OVER THAT WHEN WE GO OVER MECHANISMS
. AS WELL AS HIGHER POTENCY FOR THE IGA DIMERS AND SO NOW LET ' S TALK A LITTLE ABOUT THE SYSTEMS. THE ACE THE RECEPTOR BINDS TO THE RBD WHEN THE RBD IS THE ARRANGEMENT. IT ' S A TRIMER AND ALSO THEY CONTAINER FLOP UP OR DOWN BUT ONLY WHEN THEY ' RE UP THEY ' RE ACCESSIBLE TO THE VAs.THE ANTIBODIES WE CLONE, A NUMBER OF WHICH WERE POWERFUL, HAVE BEEN STUDIED STRUCTURALLY TO TRY TO EXPLAIN HOW THEY NEUTRALIZE AND A LAB WE ' VE BEEN DEALING WITH VERY CLOSELY HAS DEFINED FOUR DIFFERENT TEAMS OF ANTIBODIES. THE FIRST ONE SHOWN RIGHT HERE BINDS TO THE VERY SAME SURFACE AS THE RBD AND ALSO IT ONLY BINDS TO THE RBD WHEN IT ' S IN THE UP ARRANGEMENT. SO THIS COURSE ONLY BINDS UP RBDs Really COMPARABLE TO ACE 2. AND ALSO THE V GENETICS THAT ARE IN THIS TEAM MORE THAN STOOD FOR PARTIALLY BECAUSE THE FRAMEWORKS THAT INTERACT WITH THIS EMERGE THE CDRH1 AND ALSO CDRH2 ARE ENCODED IN THE GENOME AND NOT COMPONENT OF CDRH3 FORMED THROUGHOUT THE RECOMBINATION.UNLIKE THE ANTIBODIES A GOOD DEAL OF THE BINDING POWER IS COMING FROM THE GENOME INSCRIBED PART OF THE ANTIBODY. IT MAY EXPLAIN WHY THEY'' RE OVERREPRESENTED IN THE GROUP. THERE ' S A SECOND TEAM THAT CONTAINER BIND THE RBD IN BOTH BACKWARDS AND FORWARDS SETUPS. AND ALSO THERE ARE SOME EXTREMELY INTERESTING INSTANCES IN THIS TEAM FOR MECHANISMS OF NEUTRALIZATION AS WELL AS THIS GROUP DOES ANOTHER THING. IT BINDS INDEED TO THE SURFACE THAT CONNECTS WITH THE ROBINSON. THAT'' S SHOWN BELOW.– RBD, THAT ' S SHOWN RIGHT HERE. BUT IN THE TRIMER THERE'' S A NEXT DOOR RBD AND ALSO IT HAS An IMPACT NOT JUST IN ONE RBD BUT IN BOTH. IN THIS ONE IT'' S OUT THE COMMUNICATION SURFACE AREA. AND IT ' S REACHING INTO A POCKET OF THE NEXT DOOR OF RBD AND WHEN THIS OCCURS THIS THING LOCKS DOWN THE RBD SO IT REMAINS IN A DOWN ARRANGEMENT AND ALSO IT'' S OBSTRUCTED FROM BINDING ACE 2 IN 2 VARIOUS WAYS.IT ' S OBSTRUCTED SINCE IT'' S UNAVAILABLE FOR ACE 2. IT'' S LOCKED DOWN AS WELL AS ADDITIONALLY THE ACE 2 BINDING SURFACE AREA IS OCCUPIED. SO THESE SECURE DOWN ANTIBODIES REMAIN IN TRUTH VERY REALLY POTENT. AND ALSO SO FOR THERE ' S ONLY 2 EXAMPLES OF THIS KIND OF ANTIBODY. ONE IS SHOWN RIGHT HERE C144. THE OTHER WAS LATELY REPORTED. A THIRD CLASSIFICATION DOES NOT BLOCK THE ACE BINDING DIRECTLY BUT INTERFERES WITH IT IN A FEW OTHER WAY AND ALSO BINDS TO A CORRESPONDING SURFACE. THIS SORT OF ANTIBODY AN EXAMPLE IS S3O9 AND THE ANTIBODY WE DUPLICATED C135. SO I INTEGRATED BOTH BACKWARDS AND FORWARDS RBDs BUT DOES NOT BLOCK ACE 2 BINDING STRAIGHT. IT'' S ANOTHER WAY. SO 4 CLASSES. ONE COURSES STOOD FOR BY UP ONLY AS WELL AS ONE UP AND DONE INCLUDING A BLOCKING THE ACE INTERACTION DIRECTLY AND ALSO A 3RD CLASS WHICH DOES IT BY A MECHANISM WE STILL DON'' T UNDERSTAND COMPLETELY BUT CAN BIND BOTH UP AND ALSO DOWN RBDs.SO THESE
MUST BE COMPLIMENTARY WHEN YOU INCORPORATE SOMETHING SIMILAR TO THIS FOR INSTANCE WITH SOMETHING LIKE THAT. THAT'' S WHAT WE ' VE DONE AND I ' LL PROGRAM YOU NEXT AND ALSO HUMAN RBD ANTIBODIES. TEAM 1 BINDING IT THE OPEN SETUP OVERREPRESENTED VH353 IN COMPONENT BECAUSE THE BINDING IS MEDIATED IN A REALLY SIGNIFICANT FASHION BY CDRH1 AND 2 AND GROUP 1 AS WELL AS 2 TO OPEN AS WELL AS CLOSE AND SOME IMPROVE THE MOMS AND DAD AFFINITY BY UTILIZING TWO HANDS ARTIFICIALLY ESSENTIALLY.ONE HAND ON ONE RBD AS WELL AS ANOTHER PEOPLE HAND ON THE OTHER AND ONE OUTSIDE. IF THEY'' RE COMPLIMENTARY MIGHT PREVENT THE DEVELOPMENT OF AN ANTIBODY ESCAPE AND MIGHT END UP BEING A PROBLEM IN THE CORONAVIRUS. THERE'' S IT ' S AN EXPERT USED UP PAUL NASH'' S LAB CRATING AN RBD VIRUS THAT'' S A PROFICIENT VIRUS WITH THE SARS SPIKE IF YOU DO IT IN THE PRESENCE OF THE 135 ANTIBODY AND ALSO IN THE CONTROL SITUATION ALL THE ANTIBODIES THAT WE ' RE TESTING ALL 3 OF THEM THE VIRUS IS SENSITIVE. CURRENTLY IF YOU PASS IT WITH 135 IT ENDS UP BEING REALLY IMMUNE BUT NOT TO THE OTHER ANTIBODIES AND ALSO THE COMPLIMENTARY ANTIBODIES. AND IF YOU DO IT WITH BOTH ANTIBODIES YOU DO NOT SEE THE RESISTANCE SO YOU CAN SHOT RATHER HARD TO FLOW THE VIRUS IN THE PRESENCE OF THE COMBINATION OF ANTIBODIES BUT YOU JUST DO NOT SEE EMERGENCE OF RESISTANCE. THIS HOLDS TRUE NOT SIMPLY IN THIS SYSTEM BUT TRUE FOR AUTHENTIC SARS INFECTION WHICH HAS A MUCH EVEN MORE DIFFICULT TIME MAKING ANOMALIES. SO RSV THIS ONE USED HAS AN EASY TIME MAKING MUTATIONS.SARS DOES NOT AND ALSO
SARS MUTATIONS DO ARISE AND THEY DO ARISE IN THE VISIBILITY OF RESISTANCE OCCURS IN THE EXISTENCE OF ANTIBODY ARTIFICIAL INSEMINATION. SO PERSON ANTIBODIES CANISTER SELECT FOR RESISTANT VARIATIONS AND ALSO THEY BIND STRAIGHT TO THE ANTIBODY TARGET WEBSITES AND ALSO WE KNOW THIS FROM THE FRAMEWORKS AND ALSO MIXES CAN PRESENT THE APPEARANCE OF THIS RESISTANCE. SO NOW WHAT ABOUT WHAT HAPPENS TO THE ANTIBODIES IN REGARDS TO AVOIDANCE OF INFECTION OR THERAPY. THIS EXPERIMENT WAS SPENT PRICK BOWENS LAB AT COLORADO STATE AND ALSO THIS WAS IN REALITY THE EXPERIMENT I MENTIONED EARLIER THAT WAS EXTREMELY MUCH PARTICIPATION IN ASSISTING TO LAYOUT THIS AND ALSO AT SOME POINT LOOK AT THE INFORMATION HERE.THEY MUST BE THE GOLD CRITERION FOR THIS DISEASE WHEN THEY OBTAIN SICK AND
THE INFECTION THEY OBTAIN IS A RAPIDLY PROCEEDING INFECTION BY DAY 3 IS THE PEAK OF THE INFECTION IN THE LUNGS. BY DAY 5 IT ' S GONE IN REQUISITES OF THE VIRUS AND 2 KINDS OF EXPERIMENTS. AS WELL AS THE WINDOW IS 3 AND WE ' RE OFFERING IT AT 12 HOURS? THAT DO YOU GET WE UNDERSTAND THEY ' RE IN THE PETS AND YOU TIN SEE IT ' S REALLY IN 3 OUT OF FOUR OF THESE ANIMALS AND ALSO THE ANTIBODIES'WERE SUPPLIED IP. THIS PERSON OR THIS HAMSTER STOPPED WORKING BUT PERHAPS THE ANTIBODIES WERE INFUSED IN THE GUT AND ALSO NOT THE PERINEAL CAVITY AND THESE PROTECT AS WELL AS THIS ONE ISN ' T.LOOKS LIKE VERY GREAT PREVENTION AT VERY LOW DOSES OF ANTIBODIES. MORE IMPRESSIVE FOR ME IS THERAPY'.
RIGHT HERE I PROVIDED A LITTLE HIGHER DOSES DUE TO THE FACT THAT THEY WERE CONCERNED SINCE HOW IS IT GOING TO WORK IN THE SHORT DURATION OF TIME. IT KNOCKS EVERYTHING DOWN BY 4 OR FIVE ORDERS OF SIZE. SO VERY IMPRESSIVE OUTCOMES UP THIS DESIGN. WHAT ABOUT MACAQUES? THEY WERE DEEPLY ASSOCIATED WITH INTENDING THOSE EXPERIMENTS AND ALSO GETTING PERFORMED. AS WELL AS BELOW YOU PROVIDE SOMEDAY BEFORE AND ALSO YOU PROVIDE TO ME ME– THE MONKEYS INTRAOCULARLY AS WELL AS INTRANASALLY AS WELL AS YOU SEE THE KILOGRAMS AND ALSO GREAT SECURITY AND ALSO YOU SEE THE KILOGRAM DOSAGE IN A PAIR OF THE PETS AS WELL AS OUTSTANDING IN THE MACAQUE DESIGN FOR TREATMENTS. AND ALSO COWORKERS AT DAVIS WE TOOK A LOOK AT THE LUNG TISSUE AS WELL AS THE EXPERIMENT WAS DONE BY GRANTING THE ANIMALS ANTIBODY ONE DAY AFTER INFECTION.THE TOP IS VERY BEFOREHAND IN THE VERSION. BETWEEN DAYS THREE AND FOUR, SOMETHING LIKE THAT. AS WELL AS WHAT WAS DONE HERE IS TO LOOK
AT LUNG SECTIONS BY TWO PATHOLOGISTS WHO DID THIS BLINDED AND AFTERWARDS THEY RATED THE LUNGS BASED ON WHAT THEY SAW. ALVEOLI LOOKED NORMAL AND VARIOUS DEGREES OF COAGULATION THAT INDICATE PNEUMONITIS AND ALSO TOSE SUPPLIED EARLY WERE HAVING A CONSIDERABLE EFFECT ON THE LUNG. WE RECRUITED 148 INDIVIDUALS AND STUDIED THEIR IMMUNE REACTIONS IS A THIS INFECTION. IN DOING SO WE WERE ABLE TO TO DISCOVER INTRIGUING FEATURES OF HOW HUMANS REPLY TO THIS INFECTION INCLUDING THE TRUTH THAT THERE ARE CLONELY BROADENED TEAM OF LYMPHOCYTES PRODUCING HIGH-AFFINITY ANTIBODIES AND ALSO PEOPLE DO THE EXACT SAME THING IN HOW THEY NEUTRALIZE THE VIRUS. WE ' VE BEEN ABLE TO USAGE THE ANTIBODIES TO DEFINE VARIOUS COURSES OF NEUTRALIZERS AS WELL AS FREE SITES ON THE INFECTIONS THAT ARE TARGETED BY THESE ANTIBODIES.AND ALL THESE THINGS CAN HAVE A FUNCTION IN THIS PANDEMIC. BOTH FOR DEFENSE IN PEOPLE THAT AS AN EXAMPLE DON ' T REACT TO VACCINATIONS. PEOPLE LIKE ME THAT ARE OLD ENOUGH THAT HAVE A TROUBLE WITH VACCINATION REACTIONS AND IN TREATMENT FOR INDIVIDUALS WHO HAVE ACTUALLY NOT GOTTEN A VACCINATION OR HAVE AND ALSO STILL OBTAIN INFECTED. ANTIBODIES ARE BEING ESTABLISHED BY A SERIES OF VARIOUS COMPANIES WITH A WHOLE LOT OF AID FROM PROCEDURE TERMINAL VELOCITY AND THE NIH. AND THIS IS JUST A LIST AND ALSO THE TWO FURTHEST ALONG ARE REGENERON AND LILLY.THEY MAY NOT HAVE THE VERY BEST ANTIBODIES BUT OTHERS WILL CERTAINLY COME ALONG AS WELL AS I ' M REALLY POSITIVE THE AGENTS WILL BE AVAILABLE IN THE NEAR FUTURE WITH HELP FOR PREVENTION AS WELL AS THERAPY. WITH THAT I WISH TO REITERATE THAT WHAT I ' VE SPOKE ABOUT IS AN INITIATIVE BY LOTS LABORATORIES. WE DID THE ANTIBODY TOWEL– CLONING PART AND ALSO DEALT WITH CHARLIE AND PAUL ON THE NEUTRALIZATION ASSAYS AS WELL AS PAMELA BORKEMAN AS WELL AS'HER LABORATORY AND ALSO A POST-DOC IN HER LABORATORY DID ALL THE STRUCTURED FUNCTION WITH A GREAT DEAL OF HELP FROM OTHERS THERE BUT LED THAT INITIATIVE. AND ALSO THE PROFESSIONAL COWORKERS WERE ESSENTIAL IN GETTING US BEGAN SINCE THE HARDEST COMPONENT IT APPEARS TO ME AMONG THE HARDEST COMPONENTS OF THIS WHOLE THING IS THE SCIENTIFIC FACET, OBTAINING INDIVIDUALS BELOW AS WELL AS GETTING MEDICAL METHODS AND ALSO PERSUADING INDIVIDUALS IT ' S A GREAT THING TO DO.AND FINALLY AT DAVIS AND ALSO TULANE FOR THE APE RESEARCHES AND THE MOEN LABORATORY IN COLORADO FOR ALL THE SERVICE THE HAMSTERS AND ALSO I HAVEN ' T HAD TIME TO DISCUSS MICE BUT WE ' VE DONE THE SAME THING IN MICE WITH RALPH BARRISH ' S LABORATORY. WITH THAT I ' M HAPPY TO TAKE INQUIRIES, IF THERE ARE ANY? > > WE ' RE ALL PRAISING. MICHEL, MANY THANKS FOR A WONDERFUL BRILLIANT PRESENTATION OVERCOMING SOME OF THE DETAILS OF THE BODY IMMUNE SYSTEM AS WELL AS IT ' S CAPABILITY >> TO'GENERATION THIS KIND OF VERY SPECIFIC BIOMOLECULES I INFORMED THEM HAVE YOU A BIOTECHNOLOGY MANUFACTURING FACILITY IN YOUR BODY AND KEEPS A RECORD OF WHAT IT'' S USED UP THE PAST AND ALSO CAN PULL THEM OUT OF THE DOCUMENTS IF IT NEEDS TO AND HOW VACCINES ARE INTENDED TO SHIELD. IF YOU PERMIT ME I ' LL ASK THE FIRST INQUIRY BUT IF INDIVIDUALS HAVE OTHER QUESTIONS THEY WISH TO PRESENT, TO ADVISE YOU ON THE VIDEO CLIP CAST INTERNET SITE IF YOU SEE WORDS SEND LIVE RESPONSES AT THE END OF THE WEBSITES YOU TIN SEND IN An INQUIRY AS WELL AS I ' LL TRY TO PUT AHEAD TO MICHEL.MICHEL, AT THE END YOU WERE DISCUSSING THE POTENTIAL HERE OF THESE NEUTRALIZING MONOCLONAL ANTIBODIES IN THE PRIMATE MODEL'TO BE PRETTY DARNED EFFECTIVE IN
TERMS OF PREVENTION AND ALSO THERAPY. WE UNDERSTAND THAT IN THE HUMAN TESTS THAT WE ' VE HEARD A LITTLE BIT ABOUT THOUGH NONE OF THIS IS REALLY RELEASED IT ' S PRESS RELEASES IT ' S AS IF INDIVIDUALS TREATED EARLY AFTER THEY CREATED SYMPTOMS CARRY OUT IN FACT HAVE A LOWER POSSIBILITY, THIS SAY– IS A LILLY'VACCINATION AND ALSO THE A HOSPITAL STAY NUMBERS ARE INTERESTING. EVERYONE ' S WONDERING WHAT ' S THE WINDOW OF CHANCE FOR THERAPEUTICS? IT TYPE OF MAKES FEELING THIS WOULD WORK BEST IF YOU BEGIN EARLY BUT THE LENGTH OF TIME WILL THAT WINDOW EXTEND IF YOU HAVE SOMEONE WHO ' S ALREADY IN THE HOSPITAL OR WORSE YET SOMEONE IN THE ICU REALLY SICK? ARE MONOCLONAL ANTIBODIES GOING TO OPERATE IN THAT STAGE OR IS THAT LATE FOR THIS TO FUNCTION? > > I ASSUME THOSE PEOPLE GET THE LEAST GAIN FROM THIS.THEIR CONDITION IS REALLY NOT DRIVEN BY VIRAL DUPLICATION. THEIR DISEASE IS DRIVEN BY THE DAMAGE THE VIRUS HAS ACTUALLY CURRENTLY DONE. SO THEY ARE GOING TO GET THE LEAST BENEFIT. THAT ' S NOT TO SAY THERE ' LL
BE SOME ADVANTAGE BUT THE LEAST. INDIVIDUAL THAT WILL BENEFIT MANY FROM THIS ARE FOR FOR INSTANCE THE CONTACTS. IF SOMEONE IN YOUR INSTANT LOCATION IS INFECT AND KNOWN TO BE CONTAMINATED ALL'THE CALLS WOULD BENEFIT AND ALSO PEOPLE DIAGNOSED EARLY THAT DO NOT HAVE MANIFESTATION OR HAVE MILD MANIFESTATION WOULD ALSO POSSIBLY ADVANTAGES AND THE MORE DOWN YOU GO AS WELL AS THE MORE DAMAGES THE INFECTIONS DOES, AND THE LESS VIRUS THERE REMAINS IN THE SYSTEM THE LESS LIKELY ANY TREATMENT SIMILAR TO THIS WILL CERTAINLY BE An ADVANTAGE. > > ALSO, IT ' S WHETHER YOUR OWN IMMUNE SYSTEM HAS HAD A POSSIBILITY TO MOUNT ITS OWN DEFENSES AS WELL AS REGENERON STATED THE INDIVIDUALS WHO BENEFITWARD NO DOWNSIDE AT THE TIME THEY GOT THE ANTIBODY.
>> THOSE ALREADY ABSOLUTELY NO POSITIVE DIDN ' T SEEM TO OBTAIN A GREAT DEAL OF BENEFIT. > > AS WELL AS THOSE WILL BE PEOPLE LATER BECAUSE THE ADAPTIVE SYSTEM TAKES AT THE VERY LEAST A WEEK OR 2 TO REACH ANTIBODIES SO IF YOU HAVE ANTIBODIES YOU ' VE BEEN INFECTED FOR SOME TIME AND ALSO THIS FOLLOWS THE EARLY THERAPY CONCEPT. > > ALLOW ME TO START WAY BASIC INQUIRY AS WELL AS IS IT REAL THAT HIGH FONDNESS MEMORY B CELLS ARE DELETED. > > WHAT I REVEALED AS WELL AS WISH TO SHARE EXISTS ARE HIGH AFFINITY B CELLS IN THE MEMORY COMPARTMENT.IT ' S NOTICEABLE >> THERE ARE DUE TO THE FACT THAT WE ' VE CLONED THEM FROM THAT AREA. AND ALSO THE COMPARTMENT IS DEVOTED TO VARIATION AS WELL AS CREATING AN ADDITIONAL LEVEL OF IMMUNOLOGIC VARIETY. AND ALSO ANTICIPATING A MUTANT VIRUS. > >'GOT IT. YOU DISCUSSED THE OPPORTUNITY ANOMALY DEVELOPS THE OPPORTUNITY OF RETREAT SO A CONCERN COULD VIRAL RETREAT RESULT IN THE REAPPEARANCE OF THE DISEASE THAT TAKES PLACE AT ABOUT DAY 10? > > THAT ' S A GREAT CONCERN AND I PUT ON ' >> T KNOW THE SOLUTION AS WELL AS I DON ' T ENEMY THAT ' S BEEN STUDIED. IT WOULD BE AN INTERESTING KIND OF STUDY TO PERFORM TO FOLLOW THE INFECTION IN INDIVIDUALS THAT ARE SICK FOR A LONG TIME AND ALSO THAT'ARE VEREMIC FOR A LONG PERIOD OF TIME TO SEE IF IT ' S INVOLVING THOSE INDIVIDUALS. >'> IF YOU SELECTED FOR INFECTIONS STRAIN THAT NO MORE WOULD REPLY TO THE MONOCLONAL YOU ' D STILL HAVE THAT INDIVIDUAL ' S OWN IMMUNE SYSTEM TYPE OF READY TO HANDLE THE CHALLENGE.BUT WE INTEND TO SEE WHAT OCCURS. >> > > YES, IT WILL BE EXTREMELY INTERESTING TO CONSIDER AND ALSO THE LILLY TRIAL IN SPECIFIC BECAUSE IT ' S GOING WITH A SOLITARY ANTIBODY TO SEE IF THEY ARE PICKING FOR VARIANCE IN THE INDIVIDUALS THAT
ARE BEING TREATED. >> AND ALSO I ' VE SEEN A BIT OF THE INFORMATION WHICH JUST OBTAINED PUT FOR YARD IN THE LAST FEW DAYS AS WELL AS IT DOES APPEARANCE WITH THE MONOTHERAPY THERE ' S THE POSSIBILITY OF A PRESSURE ARISING WHICH IS ALREADY THERE. IT ' S NOT THAT IT OCCURRED AS An ANOMALY DURING THE INFECTION BUT THE INFECTION ALREADY HAS HETEROGENEITY IN THE GENOME SEQUENCE.THAT ' S NOT EXTREMELY COMMON MAYBE LESS THAN 1% STRESS GETS SELECTED FOR BUT IN THEIR EXPERIENCE WITH THE MONOCLONAL MONOTHERAPY THE BODY IMMUNE SYSTEM KICKED IT OUT ANYWAY BUT WE ' D LIKE TO ENSURE. > > YOU ' LL PROVIDE SOME POPULATIONS THAT WILL CERTAINLY REQUIRE THIS FORM OF TREATMENT WILL CERTAINLY BE FOR INSTANCE CANCER PEOPLE WHERE THEIR IMMUNE SYSTEMS ARE ERASED. THAT WILL CERTAINLY NOT BE An OPPORTUNITY FOR THOSE INDIVIDUALS. IN GENERAL IN HIV INDIVIDUALS LEARN THIS LESSON BEFOREHAND THAT >> MONOTHERAPIES SIMPLY WEREN ' T ADEQUATE FOR THIS KIND OF VIRAL PATHOGEN AS WELL AS HERE IT WILL BE SAFER TO HAVE MIXES LIKE THE REGENERON COMBINATION AND THE COMBINATION WITH YOU WERE EXAMINING. > > THE CONCERNS ARE ACCUMULATING AND ALSO WE ' RE ABOUT AT THE END OF THE HOUR POSSIBLY I ' LL ASK YOU ONE EVEN MORE RATHER ARBITRARILY CHOSEN AND ALSO TRIGGERED A LITTLE BIT BY THE PUBLIC DETAILS REGARDING THE TREATMENT OF THE HEAD OF STATE. WOULD YOU ANTICIPATE TREATMENT WITH STEROIDS TO EFFECT THE HIGH QUALITY OF AN ANTIBODY ACTION SUPPLYING STEROIDS. I THINK WE ' RE DISCUSSING A SCENARIO WHERE MONOCLONALS WOULD BE SUPPLIED AS A THERAPEUTIC THAT TOOK PLACE BUT WHAT DO STEROIDS PERFORM IN GENERAL TO THE ANTIBODY REACTION TO SOMEONE THAT ' S GOT INFECTED WITH COVID? SHOULD WE BE PASSING AWAY THEM AROUND WILLY-NILLY? > > I PUT ON ' T KNOW SUFFICIENT INFORMATION ABOUT WHAT TOOK PLACE IN THIS SPECIFIC SITUATION BUT THE SUGGESTION IS THE STEROID SHOULD BE GIVEN TO PEOPLE SERIOUSLY SICKNESS AND ALSO NOT EARLY BECAUSE IN TRUTH IT COULD HINDER RESISTANCE. IT ' S HARD TO HUNCH WHAT PHYSICIANS WERE ASSUMING. > > WE WON ' T GO THERE CONSIDERING THAT >> WE ' RE NOT IN THE ROOM WHERE IT HAPPENED.FINALLY, DOES ANY OF WHAT YOU DISCOVERED SO FAR ANSWER FOR HOW LONG IMMUNITY MAY BE SUSTAINED BECAUSE WE ARE ASSUMING OF THAT IN TERMS OF INFECTION AS WELL AS WILL IT MAINTAIN VEXING US BECAUSE IMMUNITY IS NOT LASTING AS LONG AS WE WISH IT'WOULD? > > I ASSUME WE NEED TO TAKE OUR LESSONS FROM THE OTHER CORONAVIRUSES. IT ' S LIKELY WE WILL HAVE RESISTANCE IN THE FEELING THAT WE WILL CERTAINLY MEMORY CELLS THAT EXIST AND ABLE TO RESPOND SWIFTLY. WHAT THAT MEANS IS OUR SERUM LEVELS OF DEGREE MAY BE TOO LOW TO SAFEGUARD United States IN MANY CASE. EVEN IF THE PRODUCT LEVELS ARE LOW AND OBTAIN CONTAMINATE WITH THE >> CORONAVIRUS IT MAY BE YOUR IMMUNE SYSTEM WILL BEGIN ENOUGH IT'WILL CERTAINLY NOT BE A SIGNIFICANT INFECTION. SO IF YOU ' VE BEEN THROUGH IT ONCE, THE CHANCES ARE YOU ' LL DOUGH FINE THE SECONDLY– DO PENALTY THE SECOND TIME TOO. THAT ' S VIRTUALLY WHAT OCCURS WITH THE VARIOUS OTHER CORONAVIRUSES. > > RIGHT. AND WE HAD THE CASE OF A GENTLEMAN FROM HONG KONG WHO OBTAINED INFECTED A SECONDLY TIME CLEARLY MEANS SECONDLY VIRUS AS WELL AS GENOMIC EXTREMELY DIFFERENT AND ALSO HAD NO SYSTEMS– SIGNS AT ALL.MICHEL, AS THE'BEEN A REMARKABLE LECTURE AS WELL AS FANTASTIC MEANS TO HONOR BILL PAUL AS WELL AS THE PRESENTATION YOU OFFERED AND THE DISCUSSION HAD WAS SIMPLY'WHAT I WAS HOPING FOR TAKING WITH EACH OTHER IMMUNOLOGY AND THE CURRENT COVID SITUATION IN TRYING TO FIND OUT HOW TO BRING THE CLINICAL DEVICE TO THE FOREFRONT TO OBTAIN US THROUGH THIS AND ALSO WE ARE GOING TO GET VIA
THIS THOUGH WE ' RE NOT QUITE THERE YET. > > IT ' S A WONDERFUL HONOR AND I ' M THRILLED TO BE ABLE TO ACCOMPLISH THIS. > > PLEASE SIGN UP WITH ME, EVERYONE IN THANKING OUR BILL PAUL LECTURER FOR 2020. HAVE A FANTASTIC REMAINDER OF THE 01:04:08.011,00:00:00.000 DAY, EVERYONE.
