>> HELLO, EVERYONE. JUST AS COVID-19 ISN'T OVER, NEITHER IS THE SEMINAR SERIES. WE'VE STILL GOT LOTS OF COVID-19 SCIENCE TO TALK ABOUT IN THIS WORST PANDEMIC IN MORE THAN 100 YEARS. SO I'M SURE YOU WILL WANT TO SIGN UP AND WATCH EVERY EPISODE OF THIS FALL'S SERIES. FOR THOSE LOOKING FOR CME TODAY'S CODE IS 43927. WHO WOULD BE BETTER TO START THIS OFF THAN OUR OWN TONY FAUCI, LEGENDARY EXPERT IN INFECTIOUS DISEASE, DIRECTOR OF NIAID SINCE 1984, CHIEF MEDICAL CENTER TO THE PRESIDENT, CONSUMMATE SCIENTIST, WISE AND COMPASSIONATE PHYSICIAN, VISIONARY MANAGER OF RESOURCES, WORLD CLASS COMMUNICATOR TO ALL AUDIENCES, HE SERVED SEVEN PRESIDENTS AS HE LED RESEARCH ON HIV, INFLUENZA, EBOLA, ZIKA, AND MUCH, MUCH MORE. HE WAS A MAJOR ARCHITECT OF WHAT MIGHT BE CONSIDERED THE MOST AMBITIOUS AND COMPASSIONATE PROGRAM EVER ACROSS THE WORLD, PEPFAR. NOW ESTIMATED TO HAVE SAVED OVER 20 MILLION LIVES, BY PROVIDING ACCESS TO ANTIRETROVIRAL THERAPY FOR HIV. AND OF COURSE SINCE JANUARY 2020 HE HAS BEEN THE WORLD'S MOST RESPECTED LEADER IN THE RESEARCH EFFORT TO ADDRESS THE COVID-19 PANDEMIC. DURING 2020 AND 2021, TONY WAS MY DAILY AND OFTEN ALSO NIGHTLY TELEPHONE PARTNER IN INSTITUTING A 24/7 ALL-HANDS ON DECK TO BRING THE POWER TO SCIENCE TO BEAR ON THIS CRY IS. I BELIEVE THE RESULTS FOR WHICH ALL OF YOU AND NIH SHOULD TAKE PARTICULAR PRIDE WILL BE RECORDED LIE HISTORIANS OF YOU AN OF SCIENCES FINAL HOURS, INCLUDING DEVELOPMENT, TESTING, APPROVAL OF mRNA VACCINE IN 11 MONTHS. IF IT'S FOUR MONTHS OR MORE SINCE YOUR LAST BOOSTER, GET YOUR NEW BIVALENT BOOSTER NOW. TONY HAS BEEN THE VOICE OF TRUTH ABOUT THE PANDEMIC THROUGH THE TUMULTUOUS TWO YEARS, NEVER ONE TO SUGARCOAT, GAVE IT TO US STRAIGHT, MOST AMERICANS APPRECIATED THAT. ON THE SILLY SIDE THAT LED TO FAUCI BOBBLEHEADS AND FAUCI DOUGHNUTS. BUT ON THE MORE DISTURBING SIDE THAT LET TO ATTACKS BY POLITICALLY MOTIVATED INDIVIDUALS WHO CHOSE TO DISTRACT FROM THEIR OWN FAILINGS BY SEEKING TO DEMONIZE THE DEVOTED PUBLIC SERVANT. I TRUST THAT HISTORY WILL JUDGE VITRIOLIC CRITICS APPROPRIATELY AS THE SELF-SERVING DISTORTERS OF THE TRUTH THAT THEY HAVE BECOME. DESPITE THOSE ATTACKS ON HIM AND HIS FAMILY THAT REQUIRE ARMED SECURITY DETAIL TONY CONTINUES TO LEAD WITH VISION AND DETAIL, ANNOUNCED HIS INTENTIONS TO STEP DOWN FROM HIS GOVERNMENT RESPONSIBILITIES BY THE END OF THIS YEAR. THAT IS HARD FOR ALL OF US TO IMAGINE, ME ESPECIALLY. BUT AS THE PRESIDENT TOLD HIM, NO ONE HAS EARNED THE RIGHT MORE TO STEP BACK FROM SUCH SUPER HUMAN DUTIES. FOR ME IT'S BEEN A PRIVILEGE TO BE TONY'S COLLEAGUE AND HIS FRIEND OVER MANY DECADES. AND IT DOES MAKE ME SMILE THAT WHEN I, AS NIH DIRECTOR FOR 12 YEARS, WOULD OCCASIONALLY BE ASKED BY SOMEONE WHO DIDN'T KNOW A LOT BEFORE INSTITUTION TO DESCRIBE WHAT IS IT, DR. COLLINS, YOU DO, WHAT IS THE RANGE OF YOUR RESPONSIBILITIES. I WOULD GO THROUGH THE MAIN THINGS. THE LISTENER WOULD LISTENED SURPRISED, MAYBE NOT ENTIRELY COMPELLED BY THE RESPONSE, OH, YOU OVERSEE 27 INSTITUTES? UH-HUH. A BUDGET OF $45 BILLION? WELSHING THAT'S A LOT DID -- WELL, THAT'S A LOT, UH-HUH. PROJECTS ON ALZHEIMER'S, CANCER, SICKLE CELL DISEASE, SOUNDS GOOD. BUT WAIT WHAT? YOU'RE TONY FAUCI'S BOSS? HA! THAT ALWAYS GOT THE BIGGEST RESPONSE. WELL, AS IF TONY NEEDED A BOSS, WE'RE ALL GOING TO BE INTERESTED TO SEE WHAT THE NEXT CHAPTER BRINGS. FOR TONY, 81 IS THE NEW 41. YOU'RE ABOUT TO HEAR FROM THIS REMARKABLE LEADER IN THIS FIRST LECTURE OF THE FALL SERIES ON COVID SCIENCE, SO JOIN ME IN WELCOMING THE MOST DEDICATED PUBLIC SERVICE I'VE KNOWN, TONY FAUCI. >> THANK YOU FOR THE KIND INTRODUCTION. I THANK THE ORGANIZERS OF THE SIG LECTURE SERIES FOR GIVING ME THE OPPORTUNITY TO MAKE THIS PRESENTATION TODAY. I'LL BE TALKING ABOUT COVID-19 UPDATE BUT ALSO FOCUSING ON SOME OF THE LESSONS LEARNED THROUGH OUR EXPERIENCE OVER THE LAST 2 1/2 YEARS. THE PRESENTATION OBJECTIVES ARE TO REVIEW THE CURRENT STATE OF THE PANDEMIC, AS I MENTIONED TO PRESENT LESSONS LEARNED, BUT ALSO TO DISCUSS THE PRO-ACTIVE RESEARCH AIMED AT PREPARING FOR FUTURE SURGES WITHIN THIS OUTBREAK AS WELL AS OTHER FUTURE PANDEMICS OF THIS OR OTHER PATHOGENS. FIRST, A QUICK LOOK AT THE CURRENT STATE OF COVID-19. JUST HISTORICALLY TO BRING US BACK 2 1/2+ YEARS, TO THE FIRST AWARENESS OF AN UNUSUAL VIRUS THAT HAD EMERGED OUT OF THE CORONAVIRUS FAMILY, FROM A MARKET IN THE CENTRAL PART OF CHINA, IN THE WUHAN DISTRICT CITY. IT BEGAN AS A CLUSTER OF CASES WHICH AS WE FAST FORWARD TO TODAY SEE WE'VE BEEN EXPERIENCING OVER THE LAST 2 1/2 YEARS THE MOST IMPACTFUL AND DEVASTATING PANDEMIC OF A RESPIRATORY DISEASE THAT THE WORLD HAS EXPERIENCED IN WELL OVER 100 YEARS WITH A GLOBAL NUMBER OF OVER 600 MILLION CASES, DEATHS ABOUT 6.5 MILLION WHICH IS LIKELY A SIGNIFICANT UNDERCOUNT OF DEATHS ASSOCIATED WITH THIS PANDEMIC, THE UNITED STATES UNFORTUNATELY AND PAINFULLY HAS SUFFERED DISPROPORTIONATELY GREATER THAN MOST ANY OTHER COUNTRY WITH ABOUT 100 MILLION CASES, AND NOW 2 1/2 YEARS IN, OVER ONE MILLION DEATHS. AGAIN, WHICH IS LIKELY A BIT OF AN UNDERCOUNT. THE SARS-COV-2 FAMILY HAS EMERGED OVER THE LAST 2 1/2 YEARS HAS BEEN EXTRAORDINARY IN THE NUMBER OF VARIANTS THAT HAVE SEQUENTIALLY PRESENTED THEMSELVES TO THE COMMUNITY LIKELY THROUGH A SERIES OF SELECTIVE PRESSURES. I CIRCLE IN RED WHERE WE CURRENTLY ON, THE OMICRON VARIANT, AS I'LL SHOW IN THE NEXT SLIDE HAS A NUMBER OF SUBVARIANTS, STARTING OFF WITH BA .1 AND GOING TO BA.2, 2.12.1 AND BA.5/4. IF YOU LOOK AT CASES IN THE UNITED STATES, WE HAVE HAD VARIOUS SURGES OVER THE 2 1/2 YEARS THAT HAVE BEEN REFLECTIVE OF NEW VARIANTS THAT HAVE OBSERVED, ALPHA, AND THEN DELTA YOU REMEMBER IN THE SUMMER OF 2021, FOLLOWED BY OMICRON. AT THE PEAK OF JANUARY THIS YEAR WE WERE APPROACHING ONE MILLION CASES A YEAR. NOW ALTHOUGH YEAR NOT AT A LEVEL THAT IS ACCEPTABLE, IT HAS GONE DOWN TO BETWEEN 75 AND 100,000 CASES A DAY. IF YOU LOOK AT DEATHS, IN THE UNITED STATES, AGAIN IF YOU LOOK AT THE SEVEN-DAY ROLLING AVERAGES AND PEAK OF THE OMICRON, IN JANUARY OF THIS YEAR, WE HAD OVER 3,000 DEATHS PER DAY. AGAIN, IF YOU LOOK AT WHERE WE ARE NOW, BETWEEN 350 AND 450 DEATHS PER DAY, SUBSTANTIALLY LOWER THAN WHAT WE EXPERIENCED BEFORE. HOWEVER, STILL AN UNACCEPTABLY HIGH LEVEL OF DEATHS. SO WHEN PEOPLE ASK US WHERE ARE WE IN THE OUTBREAK, WE'RE NOT IN THE FULMINANT STAGE WE EXPERIENCED AT THE PEAK OF THE OMICRON SURGE, BUT WITH MULTIPLE SUBVARIANTS WHAT WE'RE TALKING ABOUT WE STILL HAVE A CONSIDERABLE NUMBER OF CASES. NOW, THIS SLIDE IS A COMPLICATED SLIDE BUT IT'S REALLY IMPORTANT BECAUSE IF YOU GO FROM LEFT TO RIGHT, AND YOU LOOK AT THE VARIOUS COLOR CODES REPRESENTING THE VARIANTS, YOU CAN SEE HOW ONE VARIANT OVER TIME BECAUSE OF A TRANSMISSION ADVANTAGE OVER THE PRIOR VARIANT ESSENTIALLY PUSHES OFF THE SCENE THE PRIOR VARIANT THAT GETS REPLACED BY THE CURRENT VARIANT. AS YOU CAN SEE TO THE FAR RIGHT-HAND PART OF THE SLIDE, WHAT THE MEDIAN DENSITY PURPLE, YOU HAVE BA.5 AT 88.6, AND BA .4 AT 2.8, AND 4.6 AND .4. BA .4.5, IT'S WELL OVER 90% OF VARIANTS CIRCULATING IN THE UNITED STATES, ALSO RELATIVELY SPEAKING RIGHT REFLECTIVE IN THE REST OF THE WORLD. WE ALL KNOW OF THE SUCCESS OF THE VACCINES. THESE ARE THE THREE PLATFORMS. mRNA, ADENO, AND RECOMBINANT WITH ADJUVANT. IMMUNOGEN DISCOVERED HERE BY BONNIE GRAHAM AND KIZZY CORBETT, AND THE GROUP AT THE VRC, THE STABILIZED PRE-FUSION SPIKE PROTEIN, WE HAVE MULTIPLE COMPANIES INVOLVED, AND THE VACCINES AS YOU SEE ON THE RIGHT HAVE EITHER RECEIVED FULL APPROVAL AS WITH MODERNA AND BioNTech, OR AN EUA AS SHOWN WITH THE REST OF THE VACCINES ON THE SLIDE HERE. THESE ARE NOT THE ONLY VACCINES THAT ARE USED. MANY OTHERS ARE USED THROUGHOUT THE WORLD. BUT THESE ARE THE ONES THAT ARE CURRENTLY BEING DISTRIBUTED IN THE UNITED STATES. WE'VE DEVELOPED A SUCCESSFUL THERAPEUTIC TOOLKIT PREDOMINANTLY FOR OUTPATIENTS TO KEEP THEM FROM PROGRESSING TO ADVANCED DISEASE REQUIRING HOSPITALIZATION. THE MOST IMPORTANT OF WHICH THAT IS USED WIDELY NOW IS PAXLOVID, A PROTEASE INHIBITOR, ALSO CLINICAL TRIALS HAVE SHOWN BENEFIT OF REMDESIVIR, M ALNOPIRAVR, AND NOW BEBTELOVIM ARCB, EFFECTIVE AGAINST THE BA .4.5. WE HAVE PROPHYLAXIS WITH A MONOCLONAL ANTIBODY WHICH REDUCE THE 80% RISK OF DEVELOPING SYMPTOMATIC DISEASE AT SIX MONTHS COMPARED TO A PLACEBO IN A WELL-CONDUCTED CLINICAL TRIAL. SO THE QUESTION IS, WHY DO WE HAVE THE PERSISTENCE OF DAILY COVID-19 CASES THAT EVEN THOUGH THEY ARE LOWER THAN THEY WERE BEFORE, THEY ARE, AS SHOWN ON A COUPLE PREVIOUS SLIDES, THAT I SHOWED YOU, STILL AT A RATHER DISTURBING LEVEL. IT HAS TO DO WITH THE INCREASED TRANSMISSIBILITY OF THE CURRENT VARIANT, BA.5, THE MOST IMPORTANT IS WANING IMMUNITY, BOTH TO THE PRIOR INFECTION AND/OR TO VACCINATION. TOGETHER WITH THE RELAXATION OF MITIGATIONS THAT WE COMMONLY SEE WITH THE DECREASE IN THE USE OF MASKING, AND INCREASE IN USE OF INDOOR CONGREGATING EVENTS SUCH AS WEDDINGS, PARTIES, AND DINNERS. NOW, IF YOU LOOK TO WHERE WE ARE RIGHT NOW, THE CDC HAS RECOMMENDED THE FIRST UPDATED COVID-19 VACCINE WHICH IS A BIVALENT BA .4/5 COMPONENT AUTHORIZED FOR PEOPLE OVER 12 YEARS OLD, IF YOU USE THE PFIZER OR OVER 18 YEARS OLD, 18 OR OVER, IF YOU USE THE MODERNA. AND IN THE COMING WEEKS, THE CDC EXPECTS WITH THEIR ACIP TO RECOMMEND UPDATED BOOSTERS FOR PEDIATRIC GROUPS YOUNGER THAN 12 LIMIT NOW SET BY THE FDA AUTHORIZATION. SO LET'S MOVE ON NOW TO TAKE A LOOK AT SOME LESSONS LEARNED AS WELL AS THE RESEARCH THAT'S INVOLVED TOGETHER WITH THESE LESSONS LEARNED. THESE ARE THE SEVEN POINTS THAT I'M GOING TO BRIEFLY MAKE. FIRST, GLOBAL INFORMATION SHARING AND COLLABORATIONS ARE ESSENTIAL TO OUR SUCCESS. WE KNOW THAT NOW BECAUSE OF THE FACT THAT THE SHARING OF REAGENTS, SURVEILLANCE DATA, CONVALESCENT AND PATIENT SAMPLES, REAL WORLD CLINICAL DATA, ISOLATES, GENOMIC DATA HAVE BEEN EXTREMELY IMPORTANT IN OUR ABILITY TO ADDRESS THE MANY PROBLEMS THAT HAVE ARISEN OVER THE LAST 2 1/2 YEARS, AND THAT'S INFORMED RESEARCH NOT ONLY HERE IN THE UNITED STATES BUT THROUGHOUT THE WORLD. NEXT, THE EXISTING CLINICAL TRIAL INFRASTRUCTURE SHOULD BE UTILIZED. THIS IS AN EXAMPLE OF USE OF RESOURCES THAT WERE INVESTED DECADES AGO, WITH THE HIV CLINICAL TRIALS AND LEVERAGING THESE TO BE USED NOW TO TEST THE COVID-19 VACCINES. I REFER NOW TO THE COVID-19 PREVENTION NETWORK WHICH WE REFER TO AS COV PN, ESTABLISHED BY MERGING FOUR NIAID-FUNDED NETWORKS, SUCCESS UNTIL IN DEVELOPING DRUGS IN THE ACTG, PREVENTION TRIALS NETWORK SO SUCCESSFUL IN THE PRE-EXPOSURE PROPHYLAXIS WORK AS WELL AS HIV-INFECTED VACCINE TRIALS NETWORK. AS I MENTIONED, THAT'S REFERRED TO NOW AS THE COV-PN. IMPORTANTLY, FOR THE BASIC AND FUNDAMENTAL SCIENTIFIC COMMUNITY, PRIOR ADVANCES IN BASIC RESEARCH HAVE ENABLED THE RAPID VACCINE DEVELOPMENT. I ARTICULATED THAT IN A COMMENTARY IN "SCIENCE" IN APRIL OF 2021. AS I SAID IN THAT, THE SPEED AND EFFICIENCY WITH WHICH THESE HIGHLY EFFICACIOUS VACCINES THAT I SHOWED ON THE PRIOR SLIDE WERE DEVELOPED IN THEIR POTENTIAL FOR SAVING MILLIONS OF LIVES, DUE TO AN EXTRAORDINARY MULTI-DISCIPLINARY EFFORT THAT INVOLVED BASIC PRE-CLINICAL AND CLINICAL SCIENCE THAT HAD BEEN UNDERWAY OUT OF THE SPOTLIGHT, UNDER THE RADAR SCREEN, LITERALLY FOR DECADES BEFORE THE UNFOLDING OF THE COVID-19 PANDEMIC. TO THE POINT WHERE "SCIENCE" MAGAZINE, YOU MIGHT RECALL, IN DECEMBER OF 2020 DESIGNATED THE COVID-19 VACCINES AS THE BREAKTHROUGH OF THE YEAR OF 2020. AND, AGAIN, HERE ARE THE SAME VACCINES THAT WE MENTIONED WHERE WE HAVE NOW MULTIPLE VACCINES THAT ARE BEING USED WITH UP TO 94 TO 95% EFFICACY PREVENTING CLINICALLY RECOGNIZABLE DISEASE BUT AS I'M GOING TO MENTION IN A MOMENT, AND AS I MENTIONED EARLIER, THE ISSUE THAT WE HAVE IS WANING IMMUNITY WHICH HAS REQUIRED A VERY UNUSUAL APPROACH OF MULTIPLE UPDATING BOOSTERS FOR THE WANING IMMUNITY WHICH WHEN PRESENT IS REALLY QUITE SUCCESSFUL. NEXT, PROTOTYPE AND PRIORITY PATHOGEN APPROACHES ENABLED OUR ABILITY TO PREPARE FOR PANDEMICS, INCLUDING THE PRESENT ONE. WHAT DO WE MEAN BY THE EMERGING INFECTIOUS DISEASE VACCINE DEVELOPMENT APPROACH? THERE ARE TWO. PRIORITY PATHOGENS AND PROTOTYPE PATHOGENS. PRIORITY PATHOGENS MEAN YOU ACTUALLY PICK OUT A PATHOGEN AND PREEMPTIVELY MAKE A VACCINE FOR THAT. AS IS BEING DONE NOW AS WE DID WITH ZIKA, AS WE'RE DOING WITH NIPPA, AS WE DID WITH EBOLA. HOWEVER, THE OTHER IS A PROTOTYPE PATHOGEN APPROACH, TAKE FAMILIES OF PATHOGENS AND AS DESCRIBED, AND THIS CONCEPT DEVELOPED BY BONNIE GRAHAM FOR NIAID, IN WHICH MADE THE PROPOSAL OF LOOKING AT PRIOR EXPERIENCES WITH DIFFERENT FAMILIES OF PATHOGENS AND TO USE THAT EXPERIENCE TO PROVIDE A COMMONALITY OF KNOWLEDGE WITHIN THAT FAMILY THAT WOULD ALLOW US TO MOVE QUICKLY IF WITHIN THAT FAMILY A NEW PATHOGEN EMERGED. THERE ARE ABOUT 20 PATHOGEN FAMILIES OF IMPORTANCE. SEVEN OR EIGHT OF WHICH ARE OF THE HIGHEST PRIORITY. AND SHOWN ON THIS SLIDE WE ALREADY DID THAT WITH CORONAVIRUS, FOR EXAMPLE WE HAVE EXPERIENCE WITH WORK THAT WAS DONE ON SARS 1 AS WELL AS MERS, WHICH LED US OVER A PERIOD FROM 2002 TO 2020 TO GIVE US THE EXPERIENCE TO RESPOND RAPIDLY TO SARS-COV-2. AND WHAT YOU DO IS YOU APPLY THE STRATEGIES AND TOOLS OF ONE VIRUS WITHIN A FAMILY TO INFORM VACCINE DESIGN FOR RELATED VIRUSES. SAME WHAT WE DID WITH THE EARLY STUDIES ON CORONAVIRUSES. BASIC VIROLOGY, ASSAY DEVELOPMENT, ANIMAL MODELS, ANTIGENIC TARGETS, OPTIMAL PLATFORMS, WHETHER IT IS mRNA, NANOPARTICLE, ADENOVIRUS, AND OTHER VECTOR EXPRESSED, POTENTIAL IMMUNE CORRELATES AS WELL AS MANUFACTURING STRATEGIES FOR THE VACCINE. REMEMBER, IF WE DO THIS FOR EACH OF THOSE FAMILIES, WHICH IS GOING TO BE A LOT OF RESOURCES, BUT IT WILL PUT US IN GOOD STEAD FOR THE NEXT PANDEMIC THAT WE WILL INEVITABLY FACE. ANOTHER IMPORTANT LESSON WE MUST CONTINUE THE SURVEILLANCE OF THE HUMAN/ANIMAL INTERFACE. THIS IS CRITICAL. MY COLLEAGUE DAVID MOREENS AND I OVER TWO YEARS AGO, ACTUALLY, WROTE IN "CELL" THAT THE COVID-19 PANDEMIC IS A TRULY STARK REMINDER, ADDED TO THE GROWING RAPIDLY ARCHIVE OF HISTORICAL REMINDERS THAT IN THE HUMAN-DOMINATED WORLD IN WHICH HUMAN ACTIVITIES REPRESENT AGGRESSIVE DAMAGING, AND AS I HIGHLIGHT HERE, UNBALANCED INTERACTIONS WITH NATURE WE WILL INCREASINGLY PROVOKE NEW DISEASE EMERGENCES. AS MOST OF YOU KNOW, ABOUT 75% OF ALL NEW PATHOGENS IN HUMANS ARE ZOONOTIC, THEY HAVE EMERGED FROM AN ANIMAL RESERVOIR SOURCE. COGENT EXAMPLES, HIV, INFLUENZA, EBOLA, AND NOW COVID-19. HUMAN HEALTH IS INEVITABLY CONNECTED TO THE HEALTH OF ANIMALS IN OUR SHARED ENVIRONMENT, AND IN FACT RECENT STUDIES THAT WERE FIRST IN THE META ARCHIVE NOW APPEARED IN "CELL," "SCIENCE," AND PEER REVIEW, ALTHOUGH WE KEEP AN OPEN MIND OF THE ORIGIN OF COVID-19 THAT IT MAY HAVE BEEN OUT OF A LABORATORY ACCIDENT, THE OVERWHELMING EVIDENCE NOW IS SHOWING THAT IT WAS A NATURAL OCCURRENCE THAT WAS CENTERED IN THE WUHAN MARKET, WHERE EVIDENCE INDICATES THAT ANIMALS WERE BROUGHT IN FROM THE WILD THAT WERE VERY LIKELY INFECTED WITH SARS-COV-2, AND SPILLED OVER TO HUMANS IN THE SETTING OF THAT MARKET. NEXT, LONGSTANDING SYSTEMIC HEALTH AND SOCIAL INEQUITIES DRIVE PANDEMIC DISPARITIES. THIS IS A JAMA COMMENTARY THAT OUR COLLEAGUES HERE AT NIH LED BY ELISEO STABLE-PEREZ INDICATE WHAT WE HAVE EXPERIENCED THROUGHOUT THIS AND OTHER PANDEMICS. THAT THE MOST PERVASIVE DISPARITIES IN HEALTH WITHIN A PANDEMIC SETTING ARE OBSERVED AMONG AFRICAN AMERICAN AND LATINO INDIVIDUALS AND WHERE THE DATA EXISTS ALSO AMONG NATIVE AMERICANS, ALASKA NATIVES, AND PACIFIC ISLANDERS. THAT IS THE RESULT OF LONGSTANDING SYSTEMIC HEALTH AND SOCIAL INEQUITIES THAT DRIVE THESE DISPARITIES. DISCRIMINATION, LIMITED HEALTH CARE ACCESS AND USE, THE OCCUPATIONS OF MINORITY POPULATIONS THAT DISPROPORTIONATELY PUT THEM IN ESSENTIAL WORK SETTINGS WHERE REMOTE WORK OR PHYSICAL DISTANCING IS DIFFICULT IF NOT IMPOSSIBLE. THERE ARE ALSO EDUCATIONAL, INCOME, AND WEALTH GAPS, AS WELL AS ISSUES LIKE HOUSING WHERE SOME PEOPLE LIVE IN CROWDED CONDITIONS WHERE IT'S VERY HARD TO FOLLOW THE PREVENTION STRATEGIES THAT ARE RECOMMENDED TO PREVENT COVID-19. AND FINALLY, MISINFORMATION, WHICH HAS ALWAYS BEEN AND STILL IS THE ENEMY OF PUBLIC HEALTH AND PANDEMIC CONTROL. AND THESE ARE JUST SOME OF THE EXAMPLES OF THE EGREGIOUS MISINFORMATION WHICH HAS CHARACTERIZED OUR RESPONSE NOT ONLY IN THE UNITED STATES BUT THROUGHOUT THE WORLD TO COVID-19. FROM CRAZY CONSPIRACY THEORIES TO JUST FRAUDULENT CLAIMS ABOUT PRODUCTS SUCH AS HYDROXYCHLOROQUINE AND OTHERS. LET'S LOOK AHEAD NOW. IN JANUARY OF THIS YEAR, MY COLLEAGUES DAVID WARRENS, JEFF TAUBENBERGER AND I WROTE IN THE NEW ENGLAND JOURNAL ON THE URGENT NEED FOR CORONAVIRUS VACCINES, IT GOES BEYOND THAT. FIRST LET'S LOOK AT A PAN CORONAVIRUS VACCINE. AS I MENTIONED, WE SAID THERE IS AN URGENT NEED FOR THIS. THESE ARE SOME OF THE PAPERS OF WORK THAT'S ALREADY BEING DONE BY MANY OF OUR GRANTEES, AS WELL AS HERE IN THE INTRAMURAL PROGRAM. ONE OF THE PAPERS THAT JUST CAME OUT A FEW WEEKS AGO FROM ONE OF OUR GRANTEES, PAM BORKMAN, ON AN EXCITING POTENTIAL CANDIDATE, MOSAIC NANOPARTICLES THAT PROTECT AGAINST CHALLENGE BY DIVERSE VIRUSES IN ANIMAL MODELS. THERE ARE ALSO A NUMBER OF OTHER TRIALS THAT ARE DONE OUTSIDE OF THE REALM OF NIH FUNDING THAT ARE ALSO IMPORTANT. WITHIN THE CONTEXT OF NIH, NIAID HAS MADE SIX RECENT AWARDS OF ABOUT $60 MILLION FOR RESEARCH ON BROADLY PROTECTIVE CROHN VACCINES AND THESE ARE THE GRANT THAT HAVE BEEN AWARDED THUS FAR WITH MORE TO COME. IMPORTANTLY, MUCOSAL VACCINES CLEARLY ARE THE VACCINES OF THE FUTURE TO PREVENT NOT ONLY AGAINST DISEASE BUT AGAINST ACQUISITION AND TRANSMISSION, AN ISSUE THAT HAS BECOME EXTREMELY IMPORTANT IN THE CONTEXT OF CORONAVIRUS. THERE HAVE BEEN A NUMBER OF DISCUSSIONS ABOUT THIS, MOST RECENT ONE LAST MONTH IN SCIENCE IMMUNOLOGY BY ERIC TOPOL AND IKKAAWASAWI ABOUT NEED FOR NASAL VACCINES. THERE'S TRANSFORMATIONAL PROMISE OF MUCOSAL VACCINES. ONE, FASTER IMMUNITY RECALL AT THE SITE OF ENTRY AT THE MUCOSA, AFTER VIRAL EXPOSURE. THE IMPORTANCE OF BOTH INFECTION AND TRANSMISSION BLOCKING AND THEN AGAIN THE FACT THAT IT'S NEEDLE-FREE DELIVERY. YOU KNOW THE EXPERIENCE THAT WE'RE HAVING NOW WITH COVID-19 THAT EVEN PEOPLE WHO ARE VACCINATED AND BOOSTED, ALTHOUGH IT'S VERY CLEAR THAT THE PROTECTION AGAINST SEVERE DISEASE LEADING TO HOSPITALIZATION AND DEATHS, DOES NOT PROTECT VERY WELL AGAINST ACTUAL INFECTION. I MYSELF BEING AN EXAMPLE OF THAT. A PERSON WHO WAS VACCINATED, DOUBLY BOOSTED, WHO GOT INFECTED DURING THE OUTBREAK OF BA .1.21.1 IN JUNE OF THIS YEAR. IT WAS A RELATIVELY MILD ILLNESS. THAT WAS THE IMPORTANCE OF THE VACCINE AND BOOSTER BUT I STILL INDEED GOT INFECTED AND MAY HAVE TRANSMITTED IT TO OTHER PEOPLE INADVERTENTLY. THERE IS SOME GOOD ACTIVITY IN THE INTRANASAL WORK, THE BARRATT BIOTECH IN INDIA RECEIVED EMERGENCY USE APPROVAL OF ADENOVIRUS VECTOR THAT WAS A CONCEPT THAT WAS ORIGINALLY DEVELOPED THROUGH AN NIH GRANT TO MIKE DIAMOND AND HIS COLLEAGUES AT WASHINGTON UNIVERSITY. WE CAN'T DISCUSS THIS ABOUT THE FUTURE OF PANDEMICS WITHOUT TALKING ABOUT THE IMPORTANCE OF ANTI-VIRALS. I MENTIONED THAT IN MY EARLIER SLIDES TALKING ABOUT THE STATE OF COVID-19 AND OTHERS WITH PAXLOVID AND OTHERS BUT WE HAVE AN ANTI-VIRAL PROGRAM FOR PANDEMICS AIMED AT CATALYZING NEW MEDICINES TO COMBAT COVID-19 BUT TO PROTECT FOR OTHER PANDEMIC THREATS, BASED ON TWO CONCEPTS, DEVELOPMENT OF DRUGS AND MOLECULES ALREADY EXISTING, THE WAY WE DID, FOR EXAMPLE, WITH AZT DURING THE HIV SITUATION DECADES AGO, BUT ALSO THE DISCOVERY OF NEW MOLECULES BY EXPANDING THE BASIC SCIENCE KNOWLEDGE AND GETTING NEW ANTI-VIRAL MEDICINES. THIS IS A SCHEMATIC OF THE REPLICATION CYCLE OF SARS-COV-2. VERY SIMILAR IN THE CONCEPT OF WHAT WE DID IN THE DISCOVERY OF ANTIRETROVIRALS FOR HIV. WHERE YOU TARGET VULNERABLE AREAS OF REPLICATION CYCLE AND DEVELOP INHIBITORS SUCH AS POLYMERASE, PROTEASE INHIBITORS, ENTRY INHIBITORS, AND THEN GO ON TO ADVANCE DEVELOPMENT FOR DRUGS THAT WOULD HOPEFULLY BE EFFECTIVE AGAINST THIS PATHOGEN AS WELL AS FUTURE PATHOGENS THAT USE THIS TARGETED ANTI-VIRAL APPROACH. AND IN THIS REGARD, THE SPRING OF THIS YEAR WE ANNOUNCED A NUMBER OF AWARDS FOR ANTI-VIRAL DRUG DEVELOPMENT TO ESTABLISH NINE CENTERS CALLED ANTI-VIRAL DRUG DISCOVERY CENTERS, AVIDDs, LOOKING AT PATHOGENS OF PANDEMIC CONCERN INCLUDING PARAMIX VIRUSES, FLAVORY VIRUSES. SO WRAPPING UP, WHAT IS THE END GAME FOR 2022 AND BEYOND WITH REGARD TO COVID-19? I THINK WE CAN BEST EXPLAIN IT BY LOOKING AT THE VARIOUS PHASES AND ISSUES WHEN YOU'RE DEALING WITH A PANDEMIC. WE'VE BEEN THROUGH THE VERY FULMINANT PANDEMIC PHASE AND HAVE SEEN DECELERATION OF NEW CASES BUT HAPPENS AT THE END OF ALL THIS? WILL WE ERADICATE SARS-COV-2? I WOULD SAY WITH SOME CONFIDENCE THAT THE ANSWER TO THAT IS NO. BECAUSE WE'VE ONLY ERADICATED ONE VIRUS IN THE HISTORY OF HUMAN PUBLIC HEALTH. AND THAT IS SMALLPOX. BUT THERE WERE REASONS WE WERE ABLE TO DO THAT. THERE'S NO ANIMAL RESERVOIR. IT'S A PHENOTYPICALLY STABLE VIRUS. SMALLPOX THAT AFFLICTED PEOPLE CENTURIES AGO IS THE SAME I WAS VACCINATED AGAINST AS A CHILD. WE HAD A WIDELY ACCEPTABLE GLOBAL CAMPAIGN OF VACCINATION. BUT IMPORTANTLY, THIS IS CRITICAL, THE IMMUNITY THAT'S INDUCED BY VACCINE OR INFECTION WITH SMALLPOX, THE DURABILITY IS MEASURED IN DECADES AND LIKELY LIFETIME. NEXT, WHAT ABOUT ELIMINATION? CAN WE ELIMINATE SARS-COV-2? I'LL EXPLAIN IN A MOMENT WHY NOT. BUT LET'S LOOK AT THE ONES WE HAD ELIMINATED, POLIO AND MEASLES IN THE UNITED STATES. AGAIN, WE'RE DEALING WITH A PHENOTYPICALLY STABLE VIRUS. MEASLES OF DECADES AGO IS THE SAME MEASLES WE'RE SEEING NOW IN SOME DEVELOPING NATIONS. IN THE UNITED STATES, WE HAD AND STILL HAVE A WIDELY ACCEPTED NATIONAL VACCINATION CAMPAIGN AND IMPORTANTLY AGAIN FROM AN IMMUNOLOGICAL STANDPOINT THE IMMUNITY INDUCED BY EITHER INFECTION OR VACCINES OF BOTH POLIO AND MEASLES, THE DURABILITY IS MEASURED IN DECADES, AND LIKELY LIFETIME. BUT WHERE ARE WE WITH SARS-COV-2? WE KNOW THERE ARE ESTABLISHED ANIMAL RESERVOIRS, UNIQUELY THERE'S THE EVOLUTION OF GENOTYPICALLY AND PHENOTYPICALLY DIVERSE VARIANTS, AND WE'VE EXPERIENCED FIVE OF THESE IN THE LAST 2 1/2 YEARS. IMPORTANTLY, AND I MENTIONED THIS A FEW TIMES, THAT THE IMMUNITY INDUCED BY EITHER INFECTION OR VACCINE WANES OVER TIME. PARTICULARLY WITH REGARD TO PROTECTION AGAINST INFECTION. LESS SO AGAINST PROTECTION AGAINST SEVERE DISEASE. AND UNFORTUNATELY FOR US, WITH THE ANTI-VAX SITUATION IN THIS COUNTRY AND THE WORLD IS THE LACK OF WIDE ACCEPTANCE OF SAFE AND EFFECTIVE VACCINES. WE'RE DEALING WITH CONTROL. AND THE LEVEL OF CONTROL IS IMPORTANT. TO GET TO A LOW ENOUGH LEVEL, WHERE IT DOESN'T DISRUPT THE SOCIAL ORDER, THAT'S WHAT WE REFER TO WHEN WE SAY A RETURN TO NORMALCY OR ENDEMICITY, A DIFFICULT-TO-DESCRIBE SITUATION, BUT SOMEWHAT SIMILAR TO OTHER RESPIRATORY VIRUSES THAT DON'T DISTURB THE SOCIAL ORDER. IT DOESN'T INTERFERE WITH THE ECONOMY OR OUR SOCIAL INTERACTIONS. AND THAT'S RESPIRATORY VIRUS, COMMON COLD, INFLUENZA, WE'RE LOOKING AT A LEVEL THAT DOESN'T DISTURB OUR SOCIAL INTERACTIONS. TO GET THERE, WE BELIEVE WE HAVE TO HAVE THE AVAILABILITY OF INTERMITTENT VACCINATION, LIKE WE REFERRED TO JUST RECENTLY ABOUT GETTING CORONAVIRUS VACCINE AT LEAST ON A YEARLY BASIS. AS WELL AS OTHER THINGS, SUCH AS RESPIRATORY HYGIENE, ATTENTION TO VENTILATION IN INDOORS, MASKING WHERE APPROPRIATE, AND THE AVAILABILITY OF EFFECTIVE VIRUS ANTI-VIRALS AND MONOCLONAL ANTIBODIES. I WANT TO CLOSE WITH THIS LAST SLIDE. AN ARTICLE THAT DAVID MORENS, GREG FOCUS AND I WROTE IN "LANCET" 14 YEARS AGO. THAT MERGING INFECTIOUS DISEASES HAVE ALWAYS BEEN WITH US BEFORE WE EVEN RECORDED THEM, IN RECORDED HISTORY WE'VE EXPERIENCED THEM OVER OUR LIFETIME AND WE'RE IN THE MIDDLE OF ONE RIGHT NOW. THEY ARE INDEED A PERPETUAL CHALLENGE. AND THE ONLY WAY TO ADDRESS THEM AS A GLOBAL COMMUNITY IS TO BE PERPETUALLY PREPARED. AND THAT IS THE REASON WHY WE'RE SPEAKING TODAY ABOUT THE LESSONS LEARNED FROM OUR CURRENT VERY DIFFICULT EXPERIENCE THAT WE'VE HAD OVER THE LAST TWO YEARS, AND LET'S HOPE THAT OUR CORPORATE MEMORY OF THOSE LESSONS DOES NOT FADE AS WE PUT COVID-19 BEHIND US IN THE FUTURE YEARS. THANK YOU. >> THANK YOU, DR. FAUCI, FOR THE INSIGHTFUL AND INSPIRING TALK. I'M PAM SCHWARTZBERG, ON THE BEHALF OF THE STEERING COMMITTEE. I THANK YOU FOR ATTENDING THE FIRST TALK OF THE SEASON. IF YOU'RE INTERESTED, PLEASE JOIN THE COVID-19 SCIENTIFIC INTEREST GROUP, JUST SEARCH NIH AND COVID-19 SIG AND YOU'LL FIND OUT OUR WEBSITE WITH INSTRUCTIONS ON HOW TO JOIN AND THE LIST OF UPCOMING SEMINARS. NEXT SEMINAR IS OCTOBER 6. IT WILL BE MICHELE MINCI FROM STANFORD SPEAKING ON NEUROCOVID. YOU'LL FIND INFORMATION ON OUR COVID-19 SCIENTIFIC RESEARCH WORKSHOP WHICH WILL BE HELD DECEMBER 15 AND 16 THIS YEAR. AND REGISTRATION WILL BE OPENING IN THE NEXT FEW WEEKS. AND WE REALLY HOPE YOU CAN ALL ATTEND WHAT WE THINK WILL BE A VERY EXCITING AND DIVERSE WORKSHOP. AND NOW I'D LIKE TO TURN THE MIC OVER TO DR. VERONIQUE NUSSENBLATT, HOSTING QUESTIONS WITH DR. FAUCI. THANK YOU AGAIN, DR. FAUCI AND DR. NEWSEN BACK. >> WE HAVE SEVERAL QUESTIONS FOR YOU. SO, THE FIRST QUESTION HAS TO DO WITH MUCOSAL VACCINES THAT YOU DISCUSSED. SO WHAT ARE THE MAJOR CHALLENGES ANTICIPATED FOR NEXT GENERATION COVID-19 MUCOSAL VACCINES? >> WELL, THERE ARE A COUPLE CHALLENGES. THE FIRST IS, YOU KNOW, WE DON'T HAVE VERY GOOD MUCOSAL VACCINES FOR RESPIRATORY VIRUSES. I MEAN, WE DO HAVE THE FLU MIST FOR FLU, WHICH SEEMS TO BE QUITE GOOD. BUT WHAT WE HAVE NOT WORKED OUT IS THE COMBINATION OF GETTING GOOD PROTECTION AT THE SOURCE OF ENTRY IN THE UPPER RESPIRATORY MUCOSA, AT THE SAME TIME AS GETTING GOOD SYSTEMIC PROTECTION AT THE SYSTEMIC LEVEL. THE OTHER THING IS THAT SOMETHING THAT PEOPLE DON'T REALLY APPRECIATE IS THE SAFETY ISSUES BECAUSE IF YOU'RE TALKING ABOUT SPIKE PROTEIN, IT'S A VERY SOMEWHAT OF A MYSTERIOUS MOLECULE, WHAT WE'RE SEEING ABOUT SOME OF THE IMPORTANT ADVERSE EFFECTS FROM THE DISEASE ITSELF RELATED TO ABERRANT RESPONSES TO THE SPIKE PROTEIN AND SPIKE PROTEIN'S ABILITY TO INFLAME AREAS, FOR EXAMPLE, THAT HAVE TO DO WITH TASTE AND SMELL, THERE IS A SUBSTANTIAL SAFETY ISSUE. I TAKE THAT BACK. WE DON'T KNOW WHAT THE SAFETY ISSUE IS, RATHER THAN TO SAY A SUBSTANTIAL SAFETY ISSUE, THERE'S A SUBSTANTIAL SAFETY QUESTION. THE OTHER THING IS, YOU KNOW, AS AN IMMUNOLOGIST, AFTER ALL THESE YEARS, I'M NOT A MUCOSAL IMMUNOLOGIST BUT I'M STUNNED HOW LITTLE WE KNOW ABOUT MUCOSAL IMMUNITY AFTER SO MANY YEARS OF GREAT ADVANCES IN IMMUNOLOGY IN GENERAL, AND THAT MAY BE TO THE DIFFICULTY IN SAMPLING, IT'S SO EASY TO SAMPLE BLOOD AND THINGS LIKE THAT, BUT TO SAMPLE AREAS OF MUCOSA I THINK IT'S IMPORTANT. SO, IT'S LACK OF A TRACK RECORD OF GOOD MUCOSALLY ADMINISTERED VACCINES THAT WILL BE THE BIGGEST PROBLEM AS WELL AS THEORETICAL AND PERHAPS REAL SAFETY ISSUE. WHEN IT COMES TO COVID, NOT WHEN IT COMES TO OTHER VACCINES LIKE INFLUENZA WHICH WE'VE ALREADY DONE THE PROOF-OF-CONCEPT WITH FLU MIST. >> GREAT. THANK YOU. SO, THERE'S ANOTHER QUESTION THAT HAS -- THAT'S ALONG THE SAME LINES. WHY DON'T WE USE NASAL VACCINES FOR OTHER RESPIRATORY VIRUSES? >> YEAH, I JUST ANSWERED IT. THAT WE JUST HAVE NOT HAD THE -- YOU SAY WHY DON'T WE USE THEM? BECAUSE WE HAVEN'T DEVELOPED THEM. AND IT'S JUST A SIMPLE ISSUE OF THE REAL GAPS IN KNOWLEDGE OF MUCOSAL IMMUNITY. IF WE HAD A GREATER HANDLE ON MUCOSAL IMMUNITY I THINK YOU WOULD SEE A LOT MORE OF THE EFFORTS THAT ARE GOING TO BE PUT IN DEVELOPING PRODUCTS THAT MUCOSALLY ADMINISTERED. THE ORAL POLIO VACCINE IS A GI MUCOSALLY ADMINISTERED AND MECHANISM OF ACTION IS NOT TO PREVENT REPLICATION IN THE GUT BUT FROM MAKING THE NEXT STEP ENTERING INTO THE NERVOUS SYSTEM. WHEREAS IF YOU GET PAST THE FIRST STAGE OF A RESPIRATORY VIRUS CHALLENGING THE MUCOSA IN THE UPPER AIRWAY, THEN THE HORSE IS OUT OF THE BARN. YOU'RE ALREADY INFECTED. YOU REALLY HAVE TO HAVE A VERY SUBSTANTIAL DEGREE OF PROTECTIVE IMMUNITY. WE'VE NOT BEEN ABLE TO ACHIEVE THAT VERY WELL WITH MOST RESPIRATORY VIRUSES. >> THANK YOU. SO, THE NEXT QUESTION IS MORE OF A PERSONAL QUESTION. WHAT ARE YOU MOST PROUD OF FROM YOUR TENURE AT NIH? >> WOW! WELL, THERE ARE A NUMBER OF THINGS. I DON'T THINK I COULD PICK OUT ONE THING. CERTAIN THINGS HAVE TO DO WITH THE MULTIPLE HATS I WEAR. SO IF YOU'LL ALLOW ME A COUPLE MINUTES, I CAN EXPAND BECAUSE I CAN'T GIVE YOU A TWO-CENT ANSWER. I'M USUALLY SOMEBODY VERY PRECISE IN THEIR ANSWER. SO THERE'S CONTRIBUTION AS A SCIENTIST WHICH HAS TO DO WITH MY TENURE AT NIH BUT NOT NECESSARILY AS MY TENURE AS DIRECTOR. AND THAT IS THE FACT THAT I HAVE BEEN INVOLVED NOW FOR OVER 40 YEARS IN THE STUDY OF THE PATHOGENIC MECHANISMS OF HIV, AND ALONG WITH OTHER INVESTIGATORS INCLUDING HERE AT THE NIH I THINK WE'VE MADE A LOT OF PROGRESS. I'M PROUD OF IT AS A SCIENTIFIC ACCOMPLISHMENT AS WELL AS THE PRE-AIDS ERA, WHICH ALREADY TELLS YOU HOW OLD I AM, THAT I DID SOME SIGNIFICANT WORK ON AUTO-INFLAMMATORY DISEASES DEVELOPING THERAPIES FOR VASCULITIES THAT WITH FATAL, DEVELOPING THERAPIES THAT UTILIZED INFORMATION FROM CANCER INSTITUTE WHERE THEY WERE USING CHEMOTHERAPIES FOR CANCER, WE USED VERY LOW DOSE DRUGS LIKE CYCLOFOSIMIDE AND PUT IN REMISSION POLYANYITIS. WHEN I CAME, IT WASN'T ON THE RADAR SCREEN, PEOPLE THOUGHT THAT INFECTIONS WERE THINGS OF THE PAST AND YOU DIDN'T HAVE TO PAY OF ATTENTION -- MUCH ATTENTION. IT WAS IN INSIPIENT STAGES OF IMMUNOLOGY IN HUMANS AND BUILT IT INSTITUTE TO A $6 BILLION INSTITUTE OVER THE PERIOD I WAS DIRECTOR, DEVELOPING THE AIDS PROGRAM WHICH I'M PROUD OF, THAT LED TO DEVELOPMENT OF DRUGS WHICH HAVE BEEN EXTREMELY LIFE-SAVING AND TRANSFORMING THE CLINICAL COURSE OF PEOPLE WITH HIV, THAT HAS TO STAND AS ONE OF THE THINGS I FEEL MOST GOOD ABOUT. THERE WAS RELUCTANCE EARLY ON HAVING A SEPARATE AIDS PROGRAM BECAUSE PEOPLE FELT IT WOULD TAKE ATTENTION FROM OTHER DISEASES, WHICH IT DIDN'T. IF ANYTHING, I BROUGHT ATTENTION TO INFECTIOUS DISEASE. AND SOMETHING THAT HAD VERY LITTLE TO DO WITH MY LINE ITEM RESPONSIBILITIES AS DIRECTOR BUT BECAUSE I'VE HAD THE OPPORTUNITY TO BE THE ADVISER TO SEVEN PRESIDENTS NOW, ONE OF THE PRESIDENTS DEVELOPED A VERY CLOSE RELATIONSHIP WITH ME, SEVERAL DID, BUT ONE WE DID SOMETHING VERY IMPORTANT TOGETHER, AND THAT WAS THE DEVELOPMENT OF THE PEPFAR PROGRAM UNDER GEORGE W. BUSH WHERE HE GAVE ME THE MANDATE TO PUT TOGETHER A PROGRAM WHICH HAS NOW LED TO THE SAVING OF ABOUT 18 MILLION LIVES GLOBALLY. SO THAT HAD NOTHING TO DO REALLY WITH MY RESEARCH EXCEPT THAT MY RESEARCH PUT ME IN A POSITION TO GAIN THE TRUST OF THE PRESIDENTS AND MY RELATIONSHIP WITH THE PRESIDENTS ALLOWED ME TO BE IN A POSITION TO PUT THE PEPFAR PROGRAM TOGETHER. SO I KNOW THAT'S A LONG-WINDED ANSWER TO THE QUESTION BUT IT HAS TO DO WITH THE THREE HATS AS A SCIENTIST, AS AN INSTITUTE DIRECTOR, AND AS PUBLIC HEALTH OFFICIAL. >> DR. FAUCI, YOUR ANSWER IS INSPIRING AND LEADS US TO THE NEXT QUESTION, WHAT IS YOUR PROFESSIONAL ADVICE FOR PEOPLE STARTING IN THEIR CAREERS INTERESTED IN PUBLIC HEALTH? >> YOU KNOW, TO ME, IT'S FOLLOW YOUR PASSION. FIRST OF ALL, HAVE -- YOU HAVE TO BE KEENLY INTERESTED IN SOMETHING AND FEEL VERY PASSIONATE ABOUT IT BECAUSE THE ENERGY THAT YOU NEED TO PUT INTO SOMETHING, TO BE SUCCESSFUL WITH IT, IT HAS TO BE A PROBLEM, IN MY MIND, THAT PICK OUT A PROBLEM THAT'S RELEVANT. YOU KNOW, THERE ARE SOME PROBLEMS THAT YOU CAN DO A LOT OF EXPERIMENTS ON THAT ARE NOT PARTICULARLY RELEVANT. AND THERE ARE OTHERS THAT ARE RELEVANT BUT IT'S VERY DIFFICULT TO DEVELOP THE RIGHT KIND OF QUESTIONS TO ANSWER THEM. PICK OUT SOMETHING THAT YOU CAN ACTUALLY WORK ON, EVEN IF IT'S FUNDAMENTALLY A BASIC SCIENCE QUESTION. THAT WOULD HAVE SOME CONNECTION TO SOMETHING YOU CAN FEEL VERY STRONGLY ABOUT. AND DON'T WORRY ABOUT WHAT OTHER PEOPLE THINK ABOUT WHAT YOU DO. I MEAN, OBVIOUSLY WHEN YOU ARE TRYING TO GET A GRANT YOU HAVE TO WORRY ABOUT WHAT OTHER PEOPLE THINK ABOUT IT, BUT YOU'VE GOT TO BE THE ONE THAT REALLY FEELS VERY STRONGLY ABOUT YOUR WORK BECAUSE THAT'S GOING TO DERIVE IN YOU THE ENERGY THAT IT TAKES TO BE SUCCESSFUL IN IT. SO, YOU KNOW, SCIENCE IS AN AMAZING PROFESSION. WE SHOULD FEEL SO FORTUNATE THAT WE'VE HAD THE OPPORTUNITY THAT WAS PROBABLY GIVEN TO US BY EVERYTHING GOING BACK FROM OUR PARENTS TO MENTORS AND OTHERS WHO PUT US INTO A POSITION TO BE ABLE TO CONDUCT SCIENCE. IT'S ONE OF THE MOST SELF-FULFILLING, GRATIFYING PROFESSIONS WE CAN THINK OF. DON'T GET DISCOURAGED BY LACK OF SUCCESS. YOU KNOW, PEOPLE LOOK AT ME BECAUSE I'VE BEEN AROUND A WHILE AND I'M VERY WELL KNOWN. I HAD AS MANY FAILURES IN THE LAB THAT ALL OF YOU NOW ARE THINKING ABOUT THE FAILURES IN THE LAB. YOU KNOW, THE FIRST GROUP OF EXPERIMENTS I GOT INVOLVED WITH DIDN'T WORK VERY WELL. I WAS VERY DEPRESSED, MY FIRST PAPER, "JOURNAL OF IMMUNOLOGY," I GOT REJECTED. YOU KNOW, I THOUGHT MY CAREER WAS OVER. SO, JUST BECAUSE YOU SEE ME ON TV DOESN'T MEAN I DIDN'T GO THROUGH THE SAME THING YOU'RE ALL GOING THROUGH. >> THANK YOU. I THINK THAT ANSWER RESONATES WITH A LOT OF PEOPLE. SO, THE NEXT QUESTION HERE IS, WHAT DO YOU FORESEE AS THE BIGGEST CHALLENGE IN THE NEXT YEAR OF COVID? >> YEAH, I THINK THE BIGGEST CHALLENGE IS HOW -- IT'S A COMBINATION OF A SOCIETAL CHALLENGE AND A SCIENTIFIC CHALLENGE. THE QUESTION IS GOING TO BE, AND THAT HAS A LOT TO DO I THINK WITH ONE OF YOUR FIRST QUESTIONS, IS HOW DO WE GET THE PROTECTION OF THE COMMUNITY SUCH THAT THE LEVEL OF VIRUS IN THE COMMUNITY IS LOW ENOUGH THAT IT DOES NOT DISRUPT THE SOCIAL ORDER, BECAUSE WE REALLY CAN'T GO ON FOR A LONG TIME THE WAY WE'VE GONE ON. WE'RE ALMOST THREE FULL YEARS INTO AN ENTIRELY DISRUPTIVE PANDEMIC. IF WE HAD A VACCINE THAT WAS, A, HIGHLY EFFECTIVE, WHICH WE DO, GOOD NEWS, BAD NEWS IT DOESN'T PROTECT FOR A DURABLE PERIOD OF TIME. THE OTHER CHALLENGE IS THE FACT THAT UNLIKE THE VIRUSES THAT WE'VE CONQUERED, POLIO, SMALLPOX, MEASLES, THE ABILITY OF THIS VIRUS TO FORM VARIANTS THAT ELUDE PROTECTION OF VACCINES, MORE SO AGAINST INFECTION, THAN AGAINST SEVERE DISEASE, IS IN MANY RESPECTS UNPRECEDENTED. I MEAN, WITHIN ONE SEASON, WE'VE GONE FROM WILDTYPE TO ALPHA TO DELTA, TO THE END OF THE YEAR OMICRON. THAT IS A SCIENTIFIC AND PUBLIC HEALTH CHALLENGE, THE LIKES OF WHICH WE HAVEN'T SEEN, EVER, REALLY, WITH ANY PATHOGEN. SO THE CHALLENGE IS GOING TO BE TO DEVELOP THERAPEUTICS AS WELL AS A VACCINE THAT PREVENTS AGAINST INFECTION, HENCE YOUR QUESTION ABOUT MUCOSAL. NUMBER TWO, HAS A DURABILITY OF PROTECTION. AND THREE, IS BROADLY PROTECTIVE. SO THAT WE GET A RESPONSE AGAINST ANY ASPECT OF A SARS-COV-2, ANY VARIANT, THAT MAY NOT JUST BE CONCENTRATING ON THE SPIKE PROTEIN. THERE MAY BE OTHER COMPONENTS OF THE ANTIGENIC STRUCTURE OF THE VIRUS THAT WE NEED TO AIM AT. BUT THAT REALLY IS THE CHALLENGE TO ESSENTIALLY GET IT TO SUCH A LOW LEVEL IT DOESN'T DISRUPT US. >> THANK YOU. THERE ACTUALLY IS A QUESTION ABOUT -- IF YOU COULD COMMENT ON MUTATIONS OUTSIDE OF THE SPIKE PROTEIN, AND IF THESE MIGHT LEAD TO LONGER INFECTION OR THEIR SIGNIFICANCE. >> THERE'S A LOT WE DO NOT KNOW. WHETHER OR NOT IT'S GOING TO BE RELATED TO LONGER INFECTIONS, OR WHAT HAVE YOU, WE DON'T KNOW. BUT WE DO KNOW THAT, FOR EXAMPLE, YOU KNOW, THE BA .4 AND BA.5 AND BA .1, ET CETERA, YOU LOOK AT THE SPIKE PROTEIN IN MANY RESPECTS THEY ARE QUITE SIMILAR BUT YET HAVE DIFFERENT DEGREES OF TRANSMISSION EFFICIENCY. THEY HAVE DIFFERENT DEGREES OF OTHER PHENOTYPIC ASPECTS OF THE VIRUS. SO, THERE'S A LOT WE NEED TO KNOW. THAT'S THE REASON WHY, YOU KNOW, WHEN I PUT A RESEARCH AGENDA TOGETHER, AND PEOPLE SAY WHAT MORE DO YOU NEED TO STUDY ABOUT THE VIRUS, THERE'S A LOT. WE KNOW A LOT ABOUT THIS VIRUS, BUT THERE'S A LOT WE DON'T KNOW. WE HAD TO MAKE SOME ASSUMPTIONS EARLY ON, WHICH THANK GOODNESS WERE ASSUMPTION THAT PAID OFF, OF WHAT WE'RE GOING TO PUT IN THE VACCINE, AND THE KIND OF VACCINE THAT WE'RE GOING TO USE. SO, THE TWO QUESTIONS OF A VACCINE, THE TWO BIG PILLARS, ARE PLATFORM AND IMMUNOGEN. SO, THE PLATFORM SERVED US VERY, VERY WELL. BUT WE PROBABLY NEED TO GRADUATE TO OTHER PLATFORMS BECAUSE EVEN THOUGH mRNA IS HIGHLY ADAPTABLE, AND IT ALLOWED US, REMEMBER, TO GO FROM A PLATFORM THAT WAS AN ANCESTRAL STRAIN TO SWITCH TO A BA .4/5 BIVALENT BOOSTER IN TWO MONTHS NO WAY COULD WE DO THAT WITH PROTEIN VACCINE. ONLY mRNA ALLOWS THAT BECAUSE OF THE FLEXIBILITY OF INSERTS. NOW WE HAVE TO FIGURE OUT CAN WE DO BETTER WITH NANOPARTICLE VACCINES, FOR EXAMPLE, THAT HAVE AN ARRAY OF DIFFERENT ANTIGENIC DETERMINANTS ON IT. THOSE ARE THE KIND OF QUESTIONS THAT STILL REMAIN UNANSWERED. SO ANYBODY WHO THINKS THE VACCINE STORY IS A CLOSED RESEARCH STORY FOR COVID, BECAUSE WE HAVE THIS PHENOMENAL mRNA 93, 94, 95% EFFICACY, NO, THERE'S A LOT OF WORK TO BE DONE ON VACCINE DEVELOPMENT FOR COVID. >> GREAT. THANK YOU. THE NEXT QUESTION HAS TO DO WITH CLINICAL TRIAL NETWORKS. YOU MENTIONED IN YOUR TALK THAT THE COVID-19 PREVENTION NETWORK WAS RAPIDLY CREATED BY MERGING FOUR EXISTING NIAID-FUNDED CLINICAL TRIAL NETWORKS. DO YOU ENVISION A SIMILAR APPROACH FOR FUTURE OUTBREAKS AND WHAT DO YOU SUGGEST CAN OR SHOULD BE DONE TO STRENGTHEN U.S. CLINICAL NETWORKS TO PREPARE FOR THE NEXT OUTBREAK? >> WELL, THE ANSWER IS A RESOUNDING YES. AND THAT'S ONE OF THE THINGS, YOU KNOW, SOMETIMES IT'S VERY DIFFICULT TO USE MONEY THAT IS DESIGNATED FOR ONE THING, FOR ANOTHER. ACTUALLY, YOU CAN GET IN SOME TROUBLE IF THE APPROPRIATIONS LANGUAGE SAYS YOU NEED TO USE IT SPECIFICALLY FOR ONE PURPOSE. BUT WHEN WE PUT TOGETHER THE CLINICAL TRIALS NETWORKS, IT IS THE LARGEST GLOBAL CLINICAL TRIAL NETWORK EVER PUT TOGETHER FOR ANY DISEASE. AND YOU KNOW, IT'S THE ACTG, AIDS TREATMENT CLINICAL TRIAL GROUP, THERE'S THE VACCINE PREVENTION, THERE'S THE AIDS PREVENTION GROUP, THERE'S A WHOLE BUNCH OF THEM. WE COMPLETELY PIVOTED THEM TO BE USED TO TEST NOT ONLY THE COVID VACCINES BUT ALSO SOME OF THE THERAPIES THAT WE USE. I FORESEE ABSOLUTELY THAT WE'RE GOING TO USE THOSE FOR OTHER EMERGING INFECTIOUS DISEASES, AND I THINK THE PROOF THAT IT CAME TO THE RESCUE OF COVID BY PROVIDING A READY-MADE HIGHLY EXPERIENCED WITH CLINICAL INVESTIGATORS WHO REALLY KNEW HOW TO CONDUCT A CLINICAL TRIAL, AND THAT WAS BECAUSE OF 30 YEARS OF EXPERIENCE OF DOING IT. AND THE ANSWER IS, WHAT FURTHER DO WE HAVE TO DO? WHAT WE HAVE TO DO FURTHER IS TO MAKE SURE WE KEEP THOSE CLINICAL TRIAL NETWORKS WARM. WE DON'T LET THEM DISSIPATE. SO, YOU KNOW, PEOPLE ALWAYS ASK ME WHAT'S THE ADVICE THAT I HAVE FOR THE PERSON THAT'S GOING TO REPLACE ME. I ALWAYS SAY THERE ARE A NUMBER OF BITS OF ADVICE BUT ONE OF THEM IS MAKE SURE YOU DON'T ALLOW THE CLINICAL TRIAL APPARATUS TO ALL OF A SUDDEN GO INTO ATTRITION BECAUSE YOU DON'T HAVE A BIG OUTBREAK BECAUSE WE'RE GOING TO NEED THEM TO COME BACK AT THE NEXT INEVITABLE OUTBREAK THAT WE HAVE. WHICH I THINK WAS THE LAST SLIDE ON MY TALK. >> THANK YOU, DR. FAUCI. SO WE WANT TO BE RESPECTFUL OF YOUR TIME. YOU HAVE MANY COMMITMENTS TODAY. BUT AGAIN THANK YOU SO MUCH ON BEHALF OF THE COVID-19 SIG STEERING COMMITTEE FOR SPEAKING WITH US TODAY AND TO THE AUDIENCE, THANK YOU FOR JOINING US. WE LOOK FORWARD TO SEEING YOU AT THE NEXT WEBINAR. >> YES, THANK YOU FOR HAVING ME. IT'S BEEN A PLEASURE. TAKE CARE.