WELCOME TO THE OPEN SESSION OF THE DIVISION OF MICROBIOLOGY AND INFECTIOUS DISEASE SUBCOMMITTEE MEETING OF COUNCIL. I'M EMILY ERBELDING AND I WILL START OFF BY GIVING THE DIRECTOR'S REPORT. DO I HAVE CONTROL OF THESE SLIDES? >> DO YOU WANT CONTROL OR DO YOU WANT ME TO ADVANCE THE SLIDES? >> LET ME JUST GIVE YOU, I WILL JUST TELL YOU WHAT TO DO, HOW'S THAT. >> SO NEXT SLIDE, SO ON THIS SLIDE WE HAVE THE AGENDA TR TODAY. MY REPORT FIRST WHICH WILL INCLUDE A PERSONNEL UPDATE, IT'LL INCLUDE A SUMMARY OF RESEARCH HIGHLIGHTS AND THEN I HAVE A FEW CONCEPT CLEARANCES TO REQUEST OF COUNCIL, THE 1 IS A VERY RECENT LIMITED COMPETITION THAT WE'RE ANNOUNCING FOR REGIONAL BIOCONTAINMENT LABS AND THEN WE HAVE OUR JANUARY COUNCIL IS THE TIME WHEN WE PUT FORWARD OUR CONTRACT TOPICS FOR SBIRs EMPLOY THOSE SECOND TO AND BULLET AND AND I ALONG WITH CHRISTINA AND ACTIVITIES. AND THEY WON'T HOLD A CONCEPT CLEARANCE. FIRST I WOULD LIKE TO SAY THANK TO YOU OUR COUNCIL MEMBERS WHO SERVED, AND THEIR LAST TIME WITH US, MARK FEINBERG, AND ROBIN P A TEL WILL BE ROTATING OFF OF COUNCIL, SO THANK YOU FOR YOUR SERVICE, WE GREATLY APPRECIATE IT. NEXT SLIDE, PLEASE. I WILL INTRODUCE NEW STAFF WHO JOINED THE DIVISION SINCE THE LAST TIME WE MET, PAUL EDER IS THE SCIENTIFIC OFFICER IN THE OFFICE OF BIODEFENSE AND RESEARCH RESOURCES AND TRANSLATIONAL RESEARCH AND HE IS GOING TO LEAD THE EFFORT IN CONCEPT ACCELERATION FOR DIAGNOSTICS. PREVIOUSLY HE SERVED FOR 8 YEARS AS A SENIOR MEDICAL DIAGNOSTICS ADVISOR AT BARTA, LISA WEI, JOINED ALBERTA ALSO IN THE PROJECT VACCINE DEVELOPMENT SECTION. SHE HAS BOTH PRIVATE AND FEDERAL SECTOR EXPERIENCES, BEFORE COMING HERE AND SHE WAS MOST RECENTLY AT NEI WHERE SHE WORKED ON GENE THERAPY APREACHES. SHE ALSO RECENTLY WAS ON DETAIL TO THE NIH RADX PROGRAM WHICH WAS AN ACCELERATED PROGRAM FOR COVID-19 DIAGNOSTICS AND JEREMY STAR IS A PROGRAM OFFICER IN THE DRUG DEVELOPMENT SECTION, HE'S GOING TO WORK ON THE PORTFOLIO FOR ANTIBACTERIAL AND ANTIVIRAL AGENTS. HE WAS AT PFIZER FOR 17 YEARS BEFORE COMING HERE. NEXT SLIDE, PLEASE. [INDISCERNIBLE] IS A NURSE, SHE HAS EXTENSIVE PERIODS IN PROTOCOL DESIGN AND IMPLEMENTATION OF CLINICAL STUDIES SHE JOINED DMID, AND SHE SPENT HER LAST 6 YEARS AT THE WALTER REID ARMY INSTITUTE OF RESEARCH AND SONJA, CRANDON, SHE WAS A NURSE SPECIALIST AT NCI, AND SHE'S BEEN INVOLVED WITH VARIOUS ASPECTS OF MANAGING CLINICAL TRIALS INCLUDING TRIAL INITIATION, EXECUTION AND TRIAL MONITORING AND CHRISTINA CARDEMIL IS A MEDICAL OFFICER IN THE OFFICE OF CLINICAL MEDICAL RESOURCES. SHE HAS A WEALTH OF EXPERIENCE AND INFECTIOUS DISEASES, SHE'S COMINGS TO US FROM THE CDC, WHERE SHE SERVED FOR 10 YEARS. NEXT SLIDE, PLEASE. SO I'M GOING TO NOW TALK ABOUT A FEW HIGHLIGHTS ON DMID RESEARCH NEWS, NONCOVID RELATED DMID RESEARCH RELATED NEWS. WE RECENTLY ANNOUNCED THE RESULTS OF A CHILDHOOD PNEUMONIA STUDY THAT DEMONSTRATE THAD SHORT COURSE ANTIBIOTICS WERE EQUIVALENT TO STANDARD OF CARE IN OUTCOMES AND SUPERIOR BECAUSE OF LESS SELECTION PRESSURE THROUGH DELIVERY SO THIS IS A NIAID SPONSORED RANDOMIZED DOUBLE BLIND TRIAL IN ENROLLING CHILDREN, AND YOU CAN LOOK AT THE BLOG AND THE ID WEEK 2020 PRESENTATIONS ON THIS, ON THE OUTCOME OF THIS PROJECT. NEXT SLIDE, PLEASE; SO OVER THE PAST SEVERAL MONTHS, HHS HAS RELEASED A NUMBER OF STRATEGIC PLANS AND OUR STAFF WERE INVOLVED IN THE WRITING AND THE DEVELOPMENT AND WRITING OF MANY OF THESE. ONE WAS THE VIRAL HEPATITIS NATION STRATEGIC PLAN FOR THE UNITED STATES, THIS WAS BASED UPON 3 PRIOR NATIONAL VIRAL ACTION PLANS THAT WERE RELEASED IN THE PAST 10 YEARS AND THIS PLAN AIMS FOR THE ELIMINATION OF VIRAL HEPATITIS AS A THREAT IN THE UNITED STATES. AND THEN FIRST EVER IN HHS HISTORY IS THE RELEASE OF [AUDIO CUTS OUT ] AT THE STI BRANCH WERE INVOLVED IN WRITING, NATIONAL GOALS AND OBJECTIVES TO RESPOND TO THE STI EPIDEMIC. MANY OF YOU MIGHT BE AWARE THIS IS A PUBLIC HEALTH CRISIS AND THERE HAVE BEEN INCREASES IN RATES OF SEXUALLY TRANSMITTED INFECTIONS DRAMATICALLY OVER THE PAST 6 YEARS. AND LAST THE VACCINE'S STRATEGIC PLAN WAS ALSO RELEASED, THE ACTION PLAN FOR THE UNITED STATES WITH THE NEXT 5 YEARS, BARBARA BULLOCK WAS HEAVILY INVOLVED IN PROVIDING INPUT, NIAID INPUT INTO THIS PLAN AND IT WILL ADDRESS NEW OPPORTUNITIES AND ONGOING CHALLENGES IN IMPLEMENTING VACCINATION IN THE UNITED STATES. NEXT SLIDE, PLEASE. I JUST WANTED TO HIGHLIGHT THE FACT THAT A PHASE 2 CLINICAL TRIAL RECENTLY BEGAN ENROLLMENT, THIS TRIAL WHICH IS UNDER THE OVERSIGHT OF OUR ESTIB RANCH WILL TEST [INDISCERNIBLE] WHICH IS A GROUP T VACCINE, IT WAS TEST IT AS A GONORRHEA VACCINE, SO ACQUISITION OF GANNAOREA WOULD BE THE CLINICAL END POINT. IT OPENED LAST MONTH WITH FIRST PATIENT RECRUITED IN--FIRST PATIENT RECRUITED INTO THIS TRIAL. THIS 1 WE HOPED BASED UPON OBSERVATIONAL STUDIES THIS MIGHT BE A PROMISING STUDY IN PREVENTING GONORRHEA. NEXT SLIDE, PLEASE. SO NOW I WILL MOVE ON WITH OUR REQUESTS FOR CONCEPT CLEARANCE FOR AN FY21 CONCEPT. SO YOU MIGHT RECALL THAT DR. FAUCI MENTIONED IN HIS REPORTOT NIAID BUDGET IN THE CONSOLIDATED OMNIBUS APPROPRIATION WHICH PASSED AT THE END OF 2020, THERE WAS A 40 MILLION-DOLLAR LINE ITEM ALLOCATED TO NIAID TO SUPPORT THE 12 REGIONAL BIOCONTAINMENT LABORATORIES WHICH WERE BUILT FOLLOWING THE ANTHRAX ATTACKS 17 YEARS AGO AND TO FACILITATE THAT DIRECTIVE, WE'RE POETIC POSING A CONCEPT THAT WILL FOCUS ON UPGRADES TO THESE FACILITIES. UPGRADES, RENOVATIONS, BUILDING SYSTEMS, EQUIPMENT PURCHASE, SO THAT THEY CAN CONTINUE TO DO BIOCONTAINMENT RESEARCH WORK THAT REQUIRES THIS LEVEL OF BIOCONTAINMENT INTO THE FUTURE. SO THAT EXACT APPROPRIATION LANGUAGE WAS $40 MILLION WOULD BE EVENLY DIVIDED AMONG THE 12 RBLTOZ PREVENT, PREPARE FOR AND RESPOND TO INFECTIOUS DISEASE OUTBREAKS. SO I WOULD REQUEST THAT YOU VOTE ON WHETHER OR NOT THIS INITIATIVE, THIS 1 SEPTORS COULD GO FORWARD INTO AN INITIATIVE BY RECORDING YOUR VOTE IN THE ELECTRONIC COUNCIL BOOKS. NEXT SLIDE, PLEASE. NOW I'M GOING TO MOVE ON, AND POINT OF CARE DIAGNOSTICS PER TREPONEMA P A LLIDUM, AS YOU MAY BE AWARE CURRENT DIAGNOSTICS ARE INEFFICIENT AND OUTDATED AND WE FACE ENORMOUS CHALLENGES IN THE CONTROL AND ELIM NATION OF CIVILIS AND IN ORDER TO ACHIEVE THOSE OBJECTIVES FROM A PUBLIC AND MORE STRAIGHT FORWARD THAT MIGHT USE TOOK CARE OF MODERN MOLECULAR TECHNOLOGIES, SO THE PURPOSE OF THIS SOLICITATION WOULD BE TO ENLIST THE HELP OF SMALL BUSINESSES TO DEVELOP RAPID POINT OF CARE DIAGNOSTICS. NEXT SLIDE, PLEASE, IN OUR PROPOSED LIST OF SBIR CONTRACT TOPICS WOULD BE SOLICITATIONS FOR PROJECTS THAT WOULD IMPROVE SAMPLELE AND LIBRARY PREPARATION FOR NEXT GENERATION SEQUENCING BASED DIAGNOSTICS AND INFECTIOUS DISEASES, SO IN THIS CASE, NEXT GENERATION SEQUENCING BASED DIAGNOSTICS ARE NOT ALWAYS AUTOMATED AND SOMETIMES CAN ONLY BE RUN AT HIGH COMPLEXITY LABS AND THAT LIMITS THEIR ABILITY TO BE WIDELY USED SO THIS SO LICITATION WOULD BE TO DEVELOP GENERALIZABLE PROCEDURES FOR SAMPLE EXTRACTION AND FOR LIBRARY PREPARATION DIRECTLY FROM THE CLINICAL SAMPLES, SO THAT THERE COULD BE FASTER AND MORE ACCURATE NEXT IME NATIONAL LIBRARY OF MEDICINE SEQUENCE AND DIAGNOSTICS DEVELOPED FOR ANY INFECTIOUS DISEASE PATH. THE NEXT IN OUR LIST OF SBIR CONTRACT TOPICS WOULD BE SOLICITATIONS TO DEVELOP A MONOCLONAL EABT BODY MEDIATED INTERVENTION SAYS TO COMBAT MALARIA. AND THE SIGNIFICANCE OF THIS IS THAT PASSIVE IMMUNIZATION USING SPECIFIC MONOCLONALS EITHER AS IMMUNOTHERAPY OR AS PREEXPOSURE PROPHYLAXIS MIGHT BE A PROMISING STRATEGY FOR COMBATING MALARIA, THERE ARE DATA THAT SUGGEST THIS AND WELL CHARACTERIZED MONOCLONALS MIGHT ALSO DOWN THE ROAD INFORM VACCINE DEVELOPMENT EFFORTS. SO THIS SOLICITATION WOULD BE FOR THE DEVELOPMENT OF MONOCLONALS OR MONOCLONAL BASED CANDIDATES FOR THE PREVENTION OR TREATMENT OF THE 2 SPECIES OF PLASMODIUM ON THIS SLIDE. NEXT SLIDE, WE HAVE 1 MORE, 1 MORE SBIR CONTRACT TOPIC. TOPIC 4 WHICH WOULD BE FOR A POINT OF CARE, POINT OF CARE DIAGNOSTICS FOR ANTIMICROBIAL RESISTANT BACTERIA AND/OR PARASITIC PATHOGENS SO RAPID IDENTIFICATION OF THESE PATHOGENS AND THEIR ASSOCIATED PHENOTYPIC PROFILE ARE NEEDED IN ORDER TO DETERMINE RAPIDLY DETERMINE TREATMENT OPTIONS FOR DIARRHEAL DISEASE IN CHILDREN IN PARTICULAR. SO THIS SOLICITATION LGD BE TO DEVELOP RAPID POINT OF CARE DIAGNOSTICS THAT WOULD DETECT THESE ENTERIC PATHOGENS AND THEIR SUSCEPTIBILITY PROFILE DIRECTLY FROM PATIENTS SPECIMENS. SO I THINK THOSE 4 CONTRACT TOPICS, AND THE FY21 SOLICITATION FOR RBLs, YOU HAVE TO RECORD YOUR VOTE ON THOSE MOVING FORWARD FOR INITIATIVE DEVELOPMENT IN THE ELECTRONIC COUNCIL BOOK. >> WE JUST-- >> I HAVE A QUESTION ABOUT THE SBIR AND RBL SYSTEMS UPGRADE. >> YES. >> CONTRACT? >> YES. >> YOU SAID THE PLAN WAS TO TAKE THE RESOURCES AND DIVIDE THEM EQUALLY AMONG THE EXISTING RBLs, WHY WOULD YOU WANT TO DO THAT AND NOT ALLOW THOSE RBLs THAT ARE PERFORMING MOST SATISFILY AND MIGHT BE IN THE GREATEST NEED TO GET A GREATER SHARE? >> SO THE SIMPLE ANSWER IS BECAUSE THE CONGRESSIONAL LANGUAGE SPECIFICALLY STATED THAT THE DOLLARS WOULD BE EVENLY DIVIDED. >> OKAY, THAT'S A STRAIGHT FORWARD ANSWER, THANK YOU. >> OKAY, SO I THINK YOU CAN TAKE DOWN THIS AND PUT UP OUR NEXT FILE WHICH IS THE COVID RELATED RESEARCH UPDATE. OKAY, SO I WILL CONTINUE ON WITH PROVIDING AN UPDATE ON WHAT OUR ACTIVITY, OUR RESEARCH ACTIVITIES AND ADVANCES HAVE BEEN RELATED TO COVID-19. I'M GOING TO START BY TALKING ABOUT THERAPEUTIC OR I'M SORRY, THERAPEUTIC AND VACCINE ADVANCES, AND THEN I BELIEVE I WILL HANDOFF TO CHRISTINA CASSETTI, TO TALK ABOUT THINGS IN THE CLINICAL REALM. SO I BELIEVE THE LAST TIME WE MET WE WENT OVER THE COVID-19 VACCINE CANDIDATES THAT WERE IN LATE STAGE DEVELOPMENT AND SUPPORTED BY THE U.S. GOVERNMENT. IT WAS THE U.S. GOVERNMENT EFFORT FORMERLY KNOWN AS OPERATION WARP SPEED BUT WE DON'T USE THAT TERM ANYMORE SINCE THE INAUGURATION. SO SUPPORTED BY U.S. GOVERNMENT EFFORTS, WE WILL SAY. SO I MENTIONED THE MODERNA VACCINE WHICH WAS CO DEVELOPED WITH THE VACCINE RESEARCH CENTER HERE AT NIAID, AND THIS IS THE PHASE 3 CLINICAL TRIAL LAUNCHED AT THE END OF JULY AND REACHED THEIR END POINT AT THE END OF--EFFICACY END POINT SHOWING NOR.1% EFFICACY IN PREVENTING COVID ILLNESS AND EMERGENCY USE AUTHORIZATION WAS ISSUED BY THE FDA IN THE MIDDLE OF DECEMBER, AND NOW THEY ARE IN THE PHASE OF CROSSING OVER UNBLINDING PARTICIPANTS TO THEIR ORIGINAL RANDOMIZATION STATUS AND CROSSING OVER PLACEBOS TO RECEIVE AFTER THE VACCINATION. SO THAT WAS A TREMENDOUS SUCCESS THAT OUR FILES UNITS WERE INVOLVED IN SUPPORTING AND IMPLEMENTING THAT PROTOCOL. THE PFIZER BY ENTECH VACCINE IS AN MRNA VACCINE THAT HAD A PRETTY SIMILAR TIMELINE WITH OPENING ENROLLMENT AT THE END OF JULY AND GETTING AN EUA IN THE BEGINNING OF DECEMBER. THIS WAS NOT SUPPORTED--THE CLINICAL DEVELOPMENT WAS NOT SUPPORTED BY THE U.S. GOVERNMENT BUT THE PRODUCT WAS PURCHASED SO MANY OF YOU THAT ARE NOW GETTING YOUR VACCINES MIGHT BE RECEIVING--UNDER EUA MIGHT BE RECEIVING THE PFIZER VACCINE. FOR THE NEXT 2 VACCINES SUPPORTED BY THE U.S. GOVERNMENT EFFORT ARE VECTOR NONREPLICATING VECTOR VACCINES USING VARIOUS ADENOVIRUS VECTORS. THE 1 QUEPED IN OXFORD AND FURTHER DEVELOPED LICENSED IN THE UNITED STATES UNDER AFT RAZENECCA IS A CHIP ADD, AND 3000 PARIS PANTS AND FOLLOW UP IS ONGOING. THE JANSSEN VACCINE, WHICH IS AD 26 NONREPLICATING VECTOR, TESTED IN THE UNITED STATES AS A SINGLE DOING VACCINE HAS COMPLETED ENROLLMENT AT 44,000 AND THE PUBLIC ANNOUNCEMENT VERY RECENTLY THAT AN EFFICACY ANNOUNCEMENT WILL BE MADE VERY, VERY SOON. SO AGAIN OUR CLINICAL TRIAL SITES WERE INVOLVED IN THE RECRUITMENT AND IMPLEMENTATION OF THESE PHASE 3 EFFICACY PROTOCOLS. NOVAVAX WAS RECENT TO LAUNCH. THIS IS A RECOMBIN ANT PROTEIN VACCINE WITH AN ADJUVANT, A NOVEL ADJUVANT, THAT TRIAL IS ENROLLING VERY RAPIDLY IN THE UNITED STATES AND WE ANTICIPATE THAT WITHIN A MONTH THEY WILL BE FULLY ENROLLED AND WE'RE HOPEFUL OF COURSE THAT ALL OF THESE VACCINES ARE EFFICACIOUS AND WILL--AND THAT WILL HAVE THESE ADDITIONAL TOOLS IN OUR TOOL BOX THAT ARE RNA VACCINES AND THEN THE SANOFI, GSA WHICH IS A RECOMBIN ANT PROTEIN PRODUCT WITH AN REMARKS SO 3 MANUFACTURED BY GSK, THIS PRODUCT WILL BEGIN--IS EXPECTED TO BEGIN ENROLLMENT RELATIVELY SOON. SO THOSE ARE THE VACCINES THAT HAVE GONE INTO EFFICACY TRIALS AND GOTTEN AN EUA ISSUED OR ARE STILL ONGOING IN EFFICACY TRIALS OR STARTING TO PLAN EFFICACY TRIALS SUPPORTING SOON THAT ARE SUPPORTED BY THE U.S. GOVERNMENT EFFORT. NEXT SLIDE. >> EMILY CAN I ASK A QUESTION. IT'S A REMARKABLE ACHIEVEMENT OBVIOUSLY. I DON'T KNOW THAT ANY OF US WOULD HAVE IMAGINED THIS WOULD HAVE HAPPENED SO QUICKLY. BUT NOW WITH THE POSSIBILITY ENTERTAINED IN SOME OF OUR MINDS, JUST THE POSSIBILITY THAT THERE COULD BE STRAINS THAT MAY BE AREN'T AS TARGETED BY SOME OF THESE VACCINES, THAT MAY EMERGE, MAY EMERGE IN THE FUTURE IS THERE AN EFFORT FROM NIAID TO LOOK AT ADDRESSING THAT SITUATION THROUGH VACCINATION. >> YES. AND YOU KNOW WE CAN'T UPDATE SLIDES FREQUENTLY ENOUGH TO GET ALL OF THE MINUTE TO MINUTE EVENTS TRANSMITTED TO YOU BUT YOU--IF YOU READ THE MEDIA THIS MORNING, RECENTLY, THE FOCUS HAS BEEN ON THESE VARIANTS THAT HAVE BEEN ISOLATED IN THE UNITED KINGDOM FIRST, BUT ALSO THAT PARTICULAR VARIANT HAS BEEN FOUND IN THE UNITED STATES AND THEN ALSO, OF ADDITIONAL CONCERN WAS A VIRUS ISOLATE FIRST ISOLATED IN SOUTH AFRICA. AND INVESTIGATORS ARE STILL PERFORMING ASSAYS ON WHETHER OR NOT VACINEE SERIES POINTSIUM NEUTRALIZES GROWTH OF THESE ISOLATES BUT PARTICULARLY IN THE CASE OF SOUTH AFRICAN RELAILTED ISOLATE THAT THERE MIGHT BE LESS THAT THE ABILITY OF THE VACCINE MIGHT BE TO PROTECT MIGHT BE LESS. AND THEN IF REALLY ARE UP TO DATE, YOU MIGHT HAVE RECOGNIZE THAD IT WAS MODERNA ANNOUNCED BEFORE THE STOCK MARKET OPEN THAT THEY ARE PLANNING TO MOVE FORWARD WITH A NEW VACCINE DESIGN USING THEIR PLATFORM THAT WILL SPECIFICALLY TARGET THE VARIANT THAT HAS COME OUT THAT WAS FIRST ISOLATED FROM SOUTH AFRICA, BASED UPON THE FACT THAT THERE'S A PARTIAL REDUCTION IN NEUTRALIZING ACTIVITY IN MODERNA VACCINEE SERUM, WHEN, YOU KNOW TESTED AGAINST THAT MUTANTS PSEUDOVIRUS IS CREATED WITH THE MUSEUM TAITIONZ PATTERN OF THAT ISOLATE. SO I THINK 1 OF THE PRESS RELEASES DID STATE THAT CLINICAL TRIALS WOULD BE CONDUCTED IN COLLABORATION WITH NIAID, THAT MEANS US SO THAT'S IT RIGHT NOW. THAT'S WHAT WE KNOW. THEY HAVE TO--THEY'RE PRETTY QUICK TO GET GMP PRODUCTION, PUSHING THEM HARD AND FAST, THE M1273, THEY'RE PERFORMING THE SAME EXERCISE TO PRODUCE GMP A LOT SUITABLE FOR A CLINICAL TRIAL AND WE FULLY EXPECT THAT WE WILL DO SOME SORT OF TRIAL THAT WILL TEST THE ABILITY MAYBE AS A BOOSTER AGAINST THE M1273 OR MAYBE IN COMBINATION, WE WILL TEST THE ABILITY OF THAT TO INDUCE IMMUNE RESPONSES THAT WILL BE MORE BROADLY PROTECTIVE, AGAINST TRAINS THAT INCLUDE THESE WORRIES AND VARIANTS THAT HAVE BEEN IDENTIFIED. >> YES? >> I ASSUME THEA THE NIH, THEY ARE DOING MODELING OF SORT OF SCENARIOS AS ALL THESE OTHER VACCINES COME OUT AND HAVE SOME SORT OF EFFICACY WITH PREDICTIONS OF WHEN WE WILL BE IN VACCINE EXCESS SO THAT BASICALLY ANYBODY WHO WANTS A REASONABLE VACCINE, THERE WILL BE SOMETHING AVAILABLE. THAT WOULD BE USEFUL TO HAVE AN IDEA--I MEAN THERE'S SO MANY AND THEY ALL HAVE A REASONABLE CHANCE TO BE SAFE AND EFFECTIVE. THEY MAY VARY TO SOME DEGREE BUT YOU KNOW RIGHT NOW, AT LEAST IN CALIFORNIA, I CAN TELL YOU ALL THE NUMBER OF PEOPLE I KNOW WHO ARE MAKING CALLS, CONTINUALLY EVERY DAY TRYING TO FIND A PLACE TO SCHEDULE A VACCINATION THAT'S 65 AND ABOVE AND IT WOULD BE WONDERFUL TO KNOW WHEN THAT TYPE OF ACTIVITY WILL DISAPPEAR AND PEOPLE CAN JUST GO AND GET VACCINATED. >> YEAH, YOU START OFF BY SAYING, YOU IMAGINE PEOPLE AT NIAID ARE DOING THAT, WELL ACTUALLY THAT IS AN HHS EFFORT, GUSTOV, PERNA, GENERAL PERNA WHO HAS BEEN LEADING THE IMPLEMENTATION AND LOGISTICS EFFORT IN THE PAST ADMINISTRATION AND HE STAYED ON AND THE CURRENT ADMINISTRATION IS IN CHARGE OF THAT, YES, I THINK THAT IT'S RECOGNIZED THAT THE CHALLENGES YOU DESCRIBED ARE INDEED CHALLENGES AND THE PUBLIC HEALTH WOULD BE SERVED WELL IF THE U.S. GOVERNMENT COULD GET ON TOP OF THEM WITH SUPPLY ISSUES AND BETTER PREDICTIONS. >> I ACTUALLY JUST ASSUME NIAID IS THE U.S. GOVERNMENT. >> HA HA HA HA, WE CAN'T DO EVERYTHING, HARRY. >> EMILY CAN YOU TELL US WHETHER MODERNA IS PLANNING TO ADD AN ADDITIONAL MRNA, OR REPLACE THE EXISTING WITH A NEW MESSAGE? >> YEAH, I GUESS THE QUESTIONS--SO THE QUESTION WOULD BE, DO YOU PUT 2 MESSAGES IN 1 NANO PARTICLE ENVELOPE AND IS THAT THE BEST APPROACH FOR YOUR PHASE 1 TRIAL OR DO YOU MANUFACTURE A STAND ALONE ENVELOPED NEW VARIANT MESSAGE AND CO-ADMINISTER THEM FOR THE PURPOSE OF ADDRESSING THE OBJECTIVES OF YOUR CLINICAL TRIAL NDO YOU KNOW WHETHER THE COMPLIMENTARY NEUTRALIZATION, THE ANTIBODY RAISED TO THE SOUTH AFRICAN VARIANTAR AS ACTIVE AS THE EXISTING CIRCULATING VARIANT FLT U.S. RIGHT NOW? >> I DON'T KNOW THAT. I DON'T KNOW. >> THE NEWS RELEASE--STAN, THE NEWS RELEASE KIND OF INDICATED THAT IT WOULD BE A SEPARATE MESSAGE BUT IT WASN'T A VERY EXTENSIVE NEWS RELEASE FROM MODERNA BUT THAT'S HOW I INTERPRETED IT. >> THEY DON'T HAVE THE VACCINE CANDIDATE MADE YET SO WE DON'T HAVE SERUM FROM VACCINATED ANIMALS OR PEOPLE YET BUT IT IS A GOOD QUESTION. IT IS SOMETHING THAT WE WOULD LIKE TO, YOU KNOW TIME TRAVEL INTO THE FUTURE AND KNOW RIGHT NOW. >> WELL, PRESUMABLY, FROM INDIVIDUALS INFECT WIDE THE SOUTH AFRICAN VARIANT COULD BE USED IN CROSS NEUTRALIZATION AND GIVE US THOSE. >> YEAH, I DON'T KNOW. I DON'T KNOW IF ANYONE HAS THOSE DATA. OKAY, WELL ON THIS SLIDE, I MEAN THIS IS JUST TO ILLUSTRATE HOW FAST WE WERE PLEASED THAT WE WERE ABLE TO MOVE AND OF COWER NOW WE NEED TO MOVE FAST AGAIN BECAUSE THIS VIRUS, THERE'S A LET OF IT OUT THERE AND A LOT OF REPLICATION CYCLES AND A LOT OF MUTE O GENESIS AND THESE VARIANTS ARE EMERGING BUT COMPARED TO SARS-COVID 19, IT TOOK 20 MONTHS TO DEVELOP A VACCINE FROM THE TIME OF IEKS DENTIFICATION OF THE VIRUS TO FIRST INJECTION? A PHASE 1 TRIAL AND YOU CAN SEE THAT FOR THE CORONAVIRUS, THE SARS COV 2, THE MRNA THAT ALLOW YOU TO BE NIMBLE, THAT TOOK ONLY 65 DAYS. NEXT SLIDE, PLEASE AND THEN TO GET AN AUTHORIZED/LICENSED VACCINE--SO THESE NEW PLATFORMS HAVE NOW COME OF AGE IN WILL PROBABLY BE AN IMPORTANT PARPT OF OUR EMERGING INFECTIOUS DISEASE RESPONSE TO NEW EPIDEMICS IN THE FUTURE. NEXT SLIDE. SO I JUST WANT TO--YOU KNOW WE HAD A PANDEMIC PREPAREDNESS AND RESEARCH RESPONSE PLAN. WE WERE EXAMINING OUR ABILITY TO MOUNT AN ADEQUATE RESEARCH RESPONSE AND TO HARNESS AND COLLABORATE ACROSS DIVISIONS, I WILL SAY THAT IN 2020 EVERY BIT OF ABILITY THROUGHOUT NIAID WAS STUDENT AND POSTED AND THAT--A LOT OF LABS, A LOT OF STAFF IN EXTRAMURAL PIVOTED TO JUST FOCUS ON ALMOST EXCLUSIVELY ON SARS-COV-2 AND PREVIOUSLY THEY HAD BEEN FOCUSED ON OTHER ASPECTS OF INFECTIOUS DISEASES AND I THINK THAT INTRAMURAL AND EXTRAMURAL HAS WORKED WELL TOGETHER, I'M SURE THERE IS NOR WE CAN DO TO WORK BETTER ABOUT YOU WE IDENTIFIED IN OUR PREPAREDNESS PLAN THAT THE INTRAMURAL HAD RESPONSIBILITIES, COULD TAKE ON RESPONSIBILITIES THAT REQUIRE RAPID PIVOTING TO DO EXPERIMENTS, YOU KNOW CHANGE COURSE WITHIN A WEEK BECAUSE THEY COULD REDIRECT FUNDING QUICKLY AND EXTRAMURAL DIDN'T HAVE THAT CAPACITY BUT THEY HAD A MUCH BROADER GROUP OF RESEARCHERS IN THE FAMILY THAT COULD BE TAPPED FOR THEIR EXPERTISE IN PLANNING AND IN OVERTIME AT LEAST IN RESPONDING TO AN EPIDEMIC AND THEN ALSO, IN ORDER TO DO THESE VERY LARGE TRIALS, A LARGE NUMBER OF CLINICAL TRIAL SIZE WERE REQUIRED AND WE FORMED THE COVPN, AND USINGA DATES, CLINICAL TRIALS WORKS ALONG WITH DMID, CLINICAL TRIALS, AND THAT WAS PART OF OUR RESPONSE IN ORDER TO SUPPORT THE NEEDS OF THESE VERY, VERY LARGE EFFICACY TRIALS. SO SOME OF THE ELEMENTS THAT WE ENVISIONED BEING IMPORTANT WHEN WE WROTE DOWN OUR PREPAREDNESS AND RESPONSE PLAN MORE THAN A YEAR AGO, TURNED OUTLET TO BE EFFECTIVE IN RESPONDING TO THE EPIDEMIC. NEXT SLIDE. SO JUST TO THINK ABOUT THE IMPORTANT UNANSWERED QUESTIONS THAT REMAIN IN CLINICAL RESEARCH FOR THE VACCINES AT LEAST, WE STILL DON'T KNOW WHETHER THESE VACCINES ARE SAFE AND EFFICACIOUS IN CHILDREN AND IN PREGNANT WOMEN. OF NOTE, THE EUA ISSUED BY THE FDA DID NOT EXCLUDE PREGNANT WOMEN. PREGNANT WOMEN ARE ADULTED, THEY REASONED AND THE EFFICACY IN ADULTS WAS ESTABLISHED SO NOW IT'S A PREGNANT WOMEN'S CHOICE WHETHER SHE WILL ACCESS THE VACCINE THROUGH EUA OR NOT BUT IT WOULD BE NICE TO HAVE DAT SAN FRANCISCO, CERTAINLY SAFETY DATA IS BEING COLLECTED THROUGH REGISTRIES BUT WE PROBABLY, WE ARE CONDEMN PLATING WHAT OTHER TYPES OF STUDIES MORE CAREFULLY DESIGNED PROTECTIVE TYPES OF STUDIES AND WE NEED TO DO TRIALS IN YOUNGER AGE GROUPS SO THEY CAN BE SAFELY VACCINATED AS WELL. IT'S IMPORTANT TO KNOW WHETHER SARS-COV-2 VACCINES REDUCE INFECTIOUSNESS. THERE'S A SCANT AMOUNT OF DATA THAT SUGGESTS THAT THEY DO BUT IT WOULD BE NICE TO HAVE DATA COMING FROM DIFFERENT VAC SEEBS AND A MORE ROBUST ARRAY OF DATA THAT SPOKE TO THAT QUESTION. IT WOULD BE NICE TO KNOW WHETHER OR NOT THESE NOVEL VACCINE PLATFORMS THAT ARE NOW BEING RULED OUT AND THE NOVEL ADJUVANTS ARE SAFE IN ALL POPULATIONS. AND WE WOULD LIKE TO KNOW THE DURABILITY OF PROTECTION THAT THEY MIGHT PROVIDE AND THEN, IMPORTANTLY, WE DISCUSS THIS EARLIER, WE WOULD LIKE TO KNOW WHETHER THESE VACCINES ARE EFFECTIVE AGAINST THE NEW VALID AND RELIABLE YAPTS THAT ARE EVOLVING. NEXT SLIDE PLEASE. AND THIS IS REALLY IMPORTANT FOR EXAMPLE FOR THE BRIDGING STUDIES IN THE PEDIATRIC POPULATION AND PERHAPS FOR BRIDGING TO VACCINES THAT MIGHT COME LATER AND MIGHT ENTER OR BE READY TO ENTER EFFICACY TRIALS WHEN A LARGE PART OF THE POPULATION IS VACCINATED. I ALREADY MENTIONED THE IMPORTANCE OF DOING TRIALS IN PREGNANT WOMEN AND IN PEDIATRICS, WE NEED TO START TESTING THE NEXT GENERATION, AND DEVELOPING AND TESTING THE NEXT GENERATION OF SARS-COV-2 VACCINE BECAUSE WE RECOGNIZE WE NEED BROAD PROTECTION AND THAT MIGHT NOT BE CONFIRMED BY THE EARLY STAGE VACCINES THAT ONLY TARGET THE PROINE TEEN AND THEN WE THINK ABOUT HOW WE CAN DEVELOP THROUGH DISCOVERY AND EARLY DEVELOPMENT PAN COV2 VACCINES. SO SARS-COV-2 BUT ALSO OTHER CORONAVIRUSS. NEXT SLIDE. THERAPEUTICS WE'VE HAD CLINICAL TRIAL ADVANCES IN THIS AREA, NEXT SLIDE, PLEASE. WE--IF YOU RECALL THE LAST TIME WE MET, THE RESULTS OF THE ACT TRIAL WHICH THE FINAL REPORT WAS PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE WHICH SHOWED THAT REMDESIVIR ACCELERATED RECOVERY IN SOME HOSPITALIZED PATIENTS WITH SARS-COV-2. THERE WAS ALSO AN EMERGENCY USE AUTHORIZATION ISSUED FOR BARICITINIB, THIS WAS BASED ON ACTT-2 RESULTS. SO BARICITINIB ARTHRITIS DRUG USED IN CONJUNCTION WITH REMDESIVIR. ACTT-3 AND 4, RESULTS ARE STILL PENDING WHAT THE ADDITION OF THE IMMUNE MODULATOR IN BETA 1 A, IN HOSPITALIZED PATIENTS IN ADDITION TO THIS PATIENT IN ADDITION TO REMDESIVIR WHAT IT DOES IN ACCELERATING RECOVERY IF IT DOES ACCELERATE RECOVERY IN SARS-COV-2 PATIENTS AND ALSO ACTT-4 IS TESTING DEXAMETHA SEWN AND REMDESIVIR VERSUS BARICITINIB AND HOSPITALIZED PATIENTS WITH SARS-COV-2 AND WE EXPECT RESULTS IN ACTT-3 AND 4 TO BE ANNOUNCED OVER THE NEXT FEW MONTHS. NEXT SLIDE, PLEASE. SO NOW I WILL HAND OVER THE PODIUM AS IT WERE TO CHRISTINA CASSETTI, WHO WILL TALK ABOUT PRECLINICAL RESEARCH STUDIES AND OTHER ACTIVITY? THAIRK YOU EMILY. CAN YOU ALL HEAR ME? OKAY, SO I WILL BUILD ON WHAT EMILY JUST TOLD US AND NEXT SLIDE, PLEASE. I WANT TO CONTINUE EMPHASIZE HOW IMPORTANT IT'S BEEN TO BE MOVING FORWARD FOR VACCINE TO UNDERSTAND WHAT ARE THE CORRELATES OF PROTECTION, SO IN COLLABORATION WITH BARDA, AND UNDER LARGE GOVERNMENT OPERATION EFFORTS, WE DECIDED TO CONDUCT A LARGE PRIMARY STUDY WHERE WE'RE GOING TO LOOK AT THE CORRELATES OF PROTECTION OF 4 DIFFERENT VACCINE CANDIDATES NHPs TO UNDERSTAND IN DETAIL THE IMMUNE RESPONSES INDUCED BY THESE VACCINES. AND THERE ARE 2 REASONS FOR DOING SUCH STUDIES. THE FIRST REASON OF COURSE IS TO RECEIVE INFORMATION FROM THE PHASE 3 TRIALS AND THE INTRODUCTION WILL BE SIMILAR TO CLINICAL STUDIES AS WELL AS PRECLINICAL STUDIES IN NHPs, AND THE ADVANT CANCER CENTER OF NHPs EVER COURSE IS THAT YOU CAN DO INTENSIVE SAMPLING AND LOOK AT THE PBMSTs AND LOOK TO SEE IF THE T-CELLS HAVE ALSO A IMPORTANT ROLE FROM ROUGH ATOM TEKS AND THESE ARE REALLY HARD TO COLLECT IN PHASE 3 TRIALS AND THAT ADVANTAGE OF NHP STUDIES IS WE CAN DO DOSE STUDY SPECIALIZATION OF SPECIFIC ENDOTHELIAL THE VACCINES ARE SO EFFECTIVE, 95% EFFICACIOUS, FOR FIGHTING INFECTION SO IT'S HARD TO LOOK FOR CORRELATES TO PROTECTION, IN NHPs YOU CAN DO THOSE STUDIES WHERE YOU GIVE SUBOPTIMAL DOSE TO ALLOW FOR INFECTIONS FOR THE PURPOSE OF UNDERSTANDING WHERE THE IMMUNE RESPONSES THAT CORRELATE WITHIN PROTECTION. AND SO, CORRELATES OF PROTECTION THAT WE HOPE TO ELUC DATE DURING THIS NHP STUDIES WE HOPE WILL EXPAND BASES FOR APPROVAL TO OTHER POPULATIONS FOR EACH VACCINE BUT ALSO MIGHT HELP TO SUPPORT APPROVAL OF THE SECOND GENERATION VACCINES. SO HOPEFULLY WE WILL GET THIS IMPORTANT DATA IN THE NEXT FEW MONTHS. NEXT SLIDE, PLEASE. ALSO VERY EARLY ON IN THE PANDEMIC, WE VERY QUICKLY LEVERAGED EXISTING CONTRACTS IN DMID TO LAY THE FOUNDATIONS FOR A VERY RAPID RESEARCH RESPONSE, NAMELY, WE SET UP THE CONTRACTS TO DEVELOP STANDARDIZED ISAYS, THESE ARE CURRENTLY THESE ASSAYS HAVE BEEN UTILIZED TO MEASURE IMMUNE RESPONSE IN THIS LARGE PHASE 3 TRIALS. AND ALSO SOME OF THE ASSAYS ARE ACTUALLY BEING USED TO MEASURE THERAPEUTIC EFFICACY OF ANTIVIRAL COMPOUNDS. WE ALSO LEVERAGE THESE CONTRACTS TO DEVELOP NEW ANIMAL MODELS TO UNDERSTAND THE PATHOGENESIS OF INFECTION AS WELL AS EVALUATE COUNTERMEASURES AND NAMELY WE--OUR INVESTIGATORS DEVELOPED MICE, HAMSTERS AND NHP MODELS. AND THESE MODELS, THEY ARE CURRENTLY BEING USED TO EVALUATE EFFICACY AND TO DO THESE CORRELATES OF PRODUCTION STUDIES I JUST MENTIONED. AND FINALLY, AN IMPORTANTLY, WE ARE VERY ENGAGED IN COLLECTING RAPIDLY REAGENTS, ESPECIALLY VIRAL ISOLATES TO PUT IN OUR MAIN REPOSITORIES AND TO GROW STOCKS AND CHARACTERIZE TO ENABLE RESEARCH ANIMAL MODELS BY ALSO INVITRO. SO ALL THESE EFFORTS ARE GOING AHEAD FULL STEAM AND THEY'VE BEEN GOING--MOVING RAPIDLY SINCE THE BEGINNING OF THE PANDEMIC. NEXT SLIDE. WE ALSO LEVERAGED SOME OF THE RESEARCH NETWORKS THAT WE HAD SET UP IN DMID, MOST IMPORTANTLY THE CENTERS FOR EXCELLENCE FOR INFLUENZA RESEARCH AND SURVEILLANCE, OVER THE COURSE OF THESE YEARS. SO THESE WERE SET UP FOR THE SURVEILLANCE OF INFLUENZA AND OTHER RESPIRAT OARY INFECTION AND WITH INCENTER FRUCTURE ON 6 CONTINENTS FOR THE PURPOSE OF DOING REASSESSMENT FOR EMERGING VIRUSES AND TRY TO BED THE BIOLOGICAL FACTORS THAT DRIVE EMERGENCE, TRANSMISSION AND PATHOGENISSITY OF THIS NEW RESPIRATORY VIRUSES AND ALTHOUGH THE [INDISCERNIBLE] HAD AN EMPHASIS ON INFLUENZA THEY ALSO HAD A COMPONENT AND EMERGING COVID VIRUSES SO IT WAS EASY TO ADDRESS THE NEWLY EMERGED CORONAVIRUS. SO THEN THEY DEVELOPED NEW ASSAYS, COLLECTING PATIENT SERUM, VIRUS ISOLATES, MAKING RECOMBIN ANT PROTEINS FOR DISTRIBUTION AND ALSO THERE WERE VERY INSTRUMENTAL IN DEVELOPING THE HAMSTER MODAND HE WILL SOME EXAMPLES OF THEIR IMPORTANT PUBLICATIONS. NEXT SLIDE, PLEASE. AND ALSO--ALSO THE [INDISCERNIBLE] HAVE BEEN CONDUCTING A NATIONAL STUDY TO COMPARE SARS-COV-2 WITH THE INFLU EANS VIRUS IN THE SOUTHERN HEMISPHERE, SO THEY'RE GOING TO BE COMPARING THE DISEASE WHERE THE VECTORS FOR SEVERE OUTCOMES, THE VIRUS SHEDDING, TRYING TO UNDERSTAND HOW THE VIRUS EVOLVES DURING THE EPIDEMICS AND WHAT ARE THE EVOLUTIONARY DYNAMICS AND ALSO TO REALLY DISSECT IMMUNE RESPONSES AND LONGEVITY OF IMMUNE RESPONSES SO HOPEFULLY WE WILL HAVE IMPORTANT DATA COMING FROM THIS STUDY IN THE NEXT FEW MONTHS. NEXT SLIDE. THESE ARE ADDITIONAL PRECLINICAL FINDINGS FROM SOME OF OUR INVESTIGATORS. HERE THIS SLIDE HIGHLIGHTS CHARACTERIZATION OF THE A NEW EARLY VARIANT THE D614 G WAS CHARACTERIZED VERY QUICKLY BY MAKING RECOMBIN ANT VIRUSES AND TESTING THEM INVITRO AS WELL AS IN ANIMAL MODELS TO SHOW THIS VIRUS DIDN'T REALLY INCREASE PATHOGENESISSITY BUT IT MADE THE VIRUS A LITTLE MORE FIT FOR TRANSMISSION. AND ALSO THEY'RE DOING--OUR INVESTIGATORS THROUGH A VARIETY OF SUPPLEMENTS AND OTHER STUDIES ARE TRYING TO UNDERSTAND WHAT NATURAL HISTORY STUDIES IN HUMANS WHAT IS THE LONGEVITY OF IMINE RESPONSES AND HAD THE IMMUNE RESPONSES FROM PROTECTION AND REINFECTION. NEXT SLIDE. AND THIS IS MY LAST SLIDE. OF COURSE THERE'S A LOT OF RESEARCH THAT WE STILL NEED TO DO. WE NEED TO CONTINUE TO UNDERSTAND THE BASIC BIOLOGY OF THIS NEW VIRUS TO UNDERSTAND HOW THE VIRUS EVOLVES. WHAT IS THE ROLE OF ANIMAL RESERVOIRS IN NEW EPIDEMICS BUT ALSO ON EMERGENTS OF NEW VARIANTS. I'M SURE YOU REMEMBER THE STUDY OF THE MINK FARMS BEING INFECTED WITH THE VIRUS, SO EVERY TIME I NEW ANIMAL GETS INFECTED, THE QUESTION IS REPLICATION OF THIS VIRUS IS 1 OF THE PRESSURES ON THE VIRUS TO QUICKLY CHANGE AND REINTRODUCE NEW VARIANTS IN THE HUMAN POPULATION. WE VALUE, WE THINK IT'S IMPORTANT TO CONTINUE TO DO STRUCTURAL FUNCTIONAL STUDIES TO UNDERSTAND THE BIOLOGY OF THE VIRUS BUT ALSO TO ELUCIDATE NEW TARGETS FOR ANTII HAVE ROLL INTERVENTIONS AND ALSO UNDERSTAND EPITAUPES FOR VACCINE AND MONOCOMPLOANAL ANTIBODY DEVELOPMENT. YOU WILL HEAR 1 OF THE NEXT PRESENTATIONS ABOUT OUR DESIRE TO RENEW THE STRUCTURAL BIOLOGY CENTERS WHICH HAS BEEN THE ENGAGED IN THESE KINDS OF STUDIES. WE ARE GOING TO CONTINUE TO REFINE THE ANIMAL MODELS THAT WE ALREADY HAVE TO CONTINUE AND UNDERSTAND THE PATHOGENESIS AND TRANSMISSION OF THIS VIRUS. TO EVALUATE THE RISK, THESE NEW VARIANTS POSE TO OUR COMMUNITIES AND ALSO TO UNDERSTAND LONG COVID, RIGHT NOW WE DON'T HAVE ANY--INFECTION. WE ARE GOING TO CONTINUE TO SUPPORT AND PUSH FOR OBSERVATIONAL COURSE STUDIES IN HUMANS, TO BETTER UNDERSTAND PATHOGENESIS, INCLUDING LONG COVID AS WELL AS UNDERSTANDING CORRELATES OF PROTECTION FROM DISEASE AND TRANSMISSION AND OF COURSE AS EMILY MENTIONED WE WILL CONTINUE TO PUSH FOR DEVELOPMENT AND SECOND GENERATION VACCINES AS WELL AS IMPROVED THERAPIES AND DIAGNOSTICS. AND THAT'S ALL I HAVE AND I GUESS WE CAN OPEN IT FOR QUESTIONS FOR BOTH EMILLEGALS SKPE BAKUGAN MYSELF. >> CRISTINA, THANK YOU VERY MUCH. VERY EXCITING. WE'RULE EXCITED ABOUT VACCINES AND THERAPEUTICS BUT AS THE RESIDENT, I THINK WHAT WE SAW WAS TREMENDOUS IN TERMS OF RAPID DEPLOYMENT OF NOVEL DIAGNOSTICS IN NOVEL WAYS. WE'VE NEVER SEEN ANYTHING LIKE IT AND IT REALLY IS SORT OF THE FUTURE ARRIVING VERY FAST, NOT JUST FOR THIS VIRUS BUT HOPEFULLY FOR OTHER THINGS. BUT YOU KNOW WHEN I THINK ABOUT VARIANT EXPWS SO FORTH, I ALSO THINK ABOUT ARE WE DONE WITH DEVELOPING DIAGNOSTICS IF ARE THIS VIRUS OR WHAT ELSE DO WE NEED? A LOT OF TIMES IT'S A HARD QUESTION TO ANSWER, RIGHT? BECAUSE YOU REALLY WANT A DIAGNOSTIC THAT WILL BE ACTIONABLE, THAT'S GOING TO CHANGE SOMETHING THAT YOU DO AND SOME OF WHAT WE NEED RIGHT NOW IS MORE ON THE PUBLIC HEALTH SIDE RATHER THAN THE PATIENT CARE SIDE BUT IT MIGHT PIVOT AND BECOME SOMETHING WE NEED ON THE PATIENT CARE SIDE, DEPENDING ON WHAT THE ACTION IS. SO I JUST WANTED TO HECKINIZE THE TREMENDOUS ROLE OUT OF DIAGNOSTICS AND ALSO TO KEEP IT ON THE LIST, I NOTICED ON DR. FAUCI'S PRESENTATION THAT THERE WERE A CERTAIN NUMBER OF PROJECTS SLATED FOR DIAGNOSTICS AND THE NUMBER FELL AS THE PROJECTIONS WENT OUT TO THE FUTURE AND IT MADE ME CRINGE A LITTLE BIT TO SAY HEY WE DID REALLY WELL WITH DIAGNOSTICS BUT I'M NOT 100% SURE WE'RE DONE. >> SO MAYBE I WILL START, THANK YOU ROBIN. WE COMLITELY AGREEN CELLS THAT DIAGNOSTIC IS REALLY FUNDAMENTAL TO A GOOD RESPONSE BECAUSE THE DIAGNOSTIC SYSTEM VERY HARD TO DEPLOY VACCINES AND THERAPEUTICS SO NO QUESTIONS ABOUT THAT, THE REASON WHY THE FIGURE WAS LOW IN THE SLIDES AND COMING FROM DR. FAUCI, IS THAT THERE WAS A VERY LARGE INVESTMENT THAT WENT TO ANOTHER PART OF NIH, WHICH IS THE [INDISCERNIBLE] INSTITUTE, VERY LARGE EFFORT TO GO BACK TO MOLECULAR DIAGNOSTICS AND ALSO THE NCI INSTITUTE RECEIVED QUITE A BIT OF FUNDING TO DEVELOP AFTER SEROLOGICAL DID I AG NOOF THETICS, WE NEITHER--COLLABORATING VERY CLOSELY WITH NCI, TO LAUNCH THE NEW SEROLOGICAL CENTERS THEY HAVE AND TO PROVIDE EXPERTISE AND OUR INVESTIGATORS AS WELL TO HELP THEM. IT WAS REALLY MORE OF AN EFFORT TO DIVIDE AND CONQUER, WHERE NIAID WAS REALLY VERY HEAVILY INVOLVED IN VACCINES AND THERAPEUTICS, SO OTHER INSTITUTES REALLY JUMPED IN AND HELPED WITH THE DIAGNOSTICS, WE COMPLETED [INDISCERNIBLE]. >> THANK YOU. >> I WILL JUST ADD THAT I MEAN RADX WAS THE NAME OF THE PROGRAM THAT NABIB LED BUT THERE WERE A NUMBER OF PEOPLE FROM NIAID THAT WERE DETAILED TO HELP AS REVIEWERS OR AS PEOPLE--PROGRAMMATIC HELP IS WHAT THEY WERE DEPLOYED FOR. I THINK THE OTHER THING THAT WE'RE NOW RECOGNIZING HAPPENING WITH THE VARIANT IS THAT IT'S POSSIBLE THEY MIGHT ALSO ESCAPE DIAGNOSTICS IF THEY'RE SEIMENSED BASED TARGETS AND SO THAT'S ANOTHER EFFORT WE'RE GOING TO HAVE--THE U.S. GOVERNMENT, NOT JUST NIAID, BUT IN COLLABORATION WITH PARTNERS AT CDC AND BARDA WE WILL HAVE TO KEEP OUR EYE ON BECAUSE WE'RE NOT DONE WITH THIS EVEN THOUGH WE TWEPPED BETTER TESTS. >> UNFORTUNATELY NOT. >> I HAVE A QUESTION, JUST WONDERING, YOU KNOW, IT STRIKES ME AS PECULIAR THAT WE'RE SEEING--WHAT LOOK LIKE IMMUNE ESCAPE VARIANTS OCCURRING IN POPULATIONS WHERE I DON'T BEING THERE'S A HUGE PERCENTAGE OF THE IMMUNE PEOPLE AND I'M WONDERING WHETHER PEOPLE ARE DETERMINING ARE ALL IMMUNE O ESCAPE VARIANTS ALSO TRANSMISSION VARIANTS? THAT IS THEY TRANSMIT MORE EFFICIENTLY THEN BECAUSE MAYBE THE SELECTIVE PRESSURE IS ACTUALLY TRANSMISSION AT THIS POINT RATHER THAN IMMUNE SELECTION. AND IT'S SORT OF A COMPLICATED QUESTION, BUT LOOKING AT WHAT TO PREDICT, 1 OF THE THINGS YOU MIGHT WANT TO DO IS SAY WHAT IS THE PRESSURE THAT IS LEADING TO SELECTION OF MUTATIONS AND IT JUST SEEMS TO ME-- >> THIS IS SPARSE DATA THAT WE GOT POORLY CHARACTERIZED CONVALESCENT PLASMA, THAT MIGHT BE ALL THAT PEOPLE HAD ACCESS TO HAD IN SOME PARTS OF THE WORLD FOR THERAPY AND PARTICULARLY FOR PEOPLE WHO MIGHT HAVE A COMP PROMISED IMMUNE SYSTEM, THAT MIGHT HAVE FOSTERED--HYPOTHESIS SOME IMMUNE O LOGIC ESCAPE, I THINK SOME OF THE ISOLATES WE'VE IDENTIFIED HAVE COME FROM PEOPLE WITH THAT CLINICAL SCENARIO, BUT WE JUST DON'T KNOW ENOUGH TO DESCRIBE. >> ARE THERE POPULATIONS WHERE THERE IS, YOU KNOW IN A GENERAL POPULATION THERE'S 20 PLUS PERCENTAGE OF THE PEOPLE WHO HAVE BEEN INFEBTED IN THE POPULATION OR 30% IN FLU, USUALLY YOU WAIT TILL THERE'S A REASONABLE AMOUNT OF EXPOSURE BEFORE YOU BEGIN TO SEE ESCAPE MUTATIONS. I'M JUST--THAT'S A STUDY THAT 1 SHOULD BE ABLE TO FIGURE OUT PRETTY QUICKLY WHETHER ALL THE ESCAPE MUTATIONS ALSO HAVE TRANSMISSION POSITIVE PHENOTYPES. >> ANOTHER THEME--SORRY. >> READING OF THE LITERATURE, THERE ARE VARIATIONS THAT INCREASE TRANSMISSIBILITY THAT DO NOT RELATE TO IMMUNE O LOGIC. >> YES BUT THERE ARE VIRUSES THAT AVOID IMMUNITY THAT DON'T TRANSMIT BETTER? THAT'S THE KEY QUESTION. >> HARRY, SOME OF THESE STUDIES ARE CURRENTLY BEING DONE AND SOME ARE INVESTIGATORS--THEY'RE RECONSTRUCTING SOME OF THESE VARIANTS IN RECOMBIN ANT VIRUSES AND THEN THERE ARE SEPARATELY SEEING IF SERUM FROM PEOPLE THAT RECEIVED THE VACCINES EQUALLY NEUTRALIZE THE WILD TYPE VIRUS VARIANTS AND ALSO THAT THE SAME RECOMBIN ANT VIRUSES IN THE TRANSMISSION STUDIES AND GENESIS STUDIES IN THE HAMSTER MODEL, THEY'RE LOOKING AT EVERYTHING, NEUTRALIZATION, TRANSMISSION AND PUBLIC [INDISCERNIBLE] IN PRECLINICAL MODELS. >> GOOD. >> OUR FIRST CONCEPT IS NOT A--WE'RE RUNNING 11 MIVENUTES AHEAD, I HOPE MATTHEW IS HERE, THIS IS NIAID OFFICE OF GENOMICS AND APPLIED TECHNOLOGIES. >> MATTHEW ARE YOU THERE? >> GOOD DAY, AND I AM. THIS IS A TRANSNIAID INITIATIVE, I CAN ONLY APPEAR IN 1 SUBCOMMITTEE MEETING AT A TIME AND YOU FOLKS HAVE THE GOOD FORTUNE TO HEAR THIS CONCEPT CLEARANCE PRESENTATION, NEXT SLIDE, PLEASE. >> SO THE PURPOSE--THE TITLE OF THIS INITIATIVE IS THE NIAID CAREER DEVELOPMENT FOR ADVANCING CAREERS OF DIVERSE WORKFORCE AND IT USES THE R25 RESEARCH EDUCATION MECHANISM, THE PURPOSE OF THIS INITIATIVE IS TO PROVIDE RESEARCH TRAINING TO INSTITUTIONS WITH SUPPORT FOR CAREER DEVELOPMENT TRAINING OF EARLY CAREER RESEARCHERS FROM GROUPS UNDER REPRESENT INDEED BIOMEDICAL RESEARCH IN NIAID SPECIFIC MISSION AREAS. AS I MENTIONED THIS USES THE R25 RESEARCH EDUCATION GRANT MECHANISM. AND THIS WILL BE A NEW FUNDING OPPORTUNITY THIS CURRENT FISCAL YEAR, THE R25 FOR THOSE OF YOU NOT FAMILIAR WITH IT, IS AN INCREDIBLY FLEXIBILITY MECHANISM, IT CAN BE USED IN A VARIETY OF DIFFERENT WAYS, IT CAN BE USED TO SUPPORT EXISTING RESEARCH TRAINING EDUCATION SAY UNDER A T32 PROGRAM OR IT CAN BE USED AS A STAND ALONE PROGRAM TO DEVELOP CURRICULUM AND SUPPORTING OTHER FORMS OF RESEARCH TRAINING. THESE ARE 5 YEAR AWARDS AND THE BUDGET CAP IS $350,000 OF CORRECT COST PLUS 8% INDIRECT COST RATE FOR A FIRST YEAR TOTAL COST OF SOMEWHERE BETWEEN 1.1 AND 1.7 MILLION, AGAIN THIS IS NIAID WIDE. WE ARE ANTICIPATING SOMEWHERE BETWEEN 20-30 APPLICATIONS PER YEAR AND EXPECT TO AWARD 3-5 OF THOSE APPLICATIONS. NEXT SLIDE. NIAID RECOGNIZES THE IMPORTANCE OF ADDRESSING SCIENTIFIC WORKFORCE DIVERSITY TO INSURE WE HAVE A POOL OF HIGHLY TALENTED SCIENTISTS FROM DIVERSE BACKGROUNDS--THIS NEW R25 RESEARCH EDUCATION PROJECT GRANT AIMS TO PROVIDE RESEARCH TRAINING INSTITUTIONS WITH SUPPORT FOR CAREER DEVELOPMENT TRAINING OF EARLY CAREER RESEARCHERS FROM GROUPS UNDER REPRESENTED IN BIOMEDICAL RESEARCH AREAS OF INTEREST TO NIAID. SO TRAINEES WILL INCLUDE UNDERGRADUATE AND GRADUATE STUDENTS, POST DOCTORAL TRAINEES AS WELL AS JUNIOR FACULTY. THIS SUPPORTS CREATIVE EDUCATIONAL ACTIVITIES WITH A PRIMARY FOCUS ON MENTORING ACTIVITIES, SUCH AS PROFESSIONAL CAREER SKILLS, SCHOLARLY WRITING AND GRANTSMANSHIP AS WELL AS HANDS ON AUTHENTIC RESEARCH EXPERIENCES AND COURSES FOR SKILLS DEVELOPMENT SUCH AS THOSE SKILLS THAT WILL IMPROVE EXPERIMENTAL RIGOR AND QUANTITATIVE SKILLS, NEXT SLIDE. SUPPORT--THE PROGRAM OBJECTIVES OF THIS INITIATIVE ARE TO SUPPORT RECRUITMENT AND TRAINING OF INDIVIDUALS FROM DIVERSE BACKGROUNDS TO SERVE AS A COMPLEMENT TO ONGOING RESEARCH TRAINING EDUCATION, TO PROVIDE ADDED CAREER DEVELOPMENT SUPPORT TO MEET THE NEEDS OF INDIVIDUALS PURSUING CAREERS IN NIAID SPECIFIC MISSION AREAS TO SUPPORT INNOVATIVE CAREER DEVELOPMENT TRAINING CURRICULUM AND ACTIVITIES THAT WILL IMPROVE RESEARCH TRAINING AND PREPARATION TRAINEES TO BECOME SUCCESSFUL RESEARCH SCIENTISTS AND TO ENCOURAGE RESEARCH INTENSIVE INSTITUTIONS TO COLLABORATE WITH INSTIEWPGZS THAT HAVE A LARGE POPULATION OF POTENTIAL TRAINEES FROM UNDERREPRESENTED GROUPS AND THE ELIGIBILITY INCLUDES BOTH PUBLIC AND PRIVATE INSTITUTIONS. THE PROPOSED RESEARCH EDUCATION MUST BE DISTINCTS FROM TRAINING PROGRAMS ALREADY RECEIVING NIH SUPPORT AT THE APPLICANT INSTITUTION AND I BELIEVE THAT'S THE LAST SLIDE. YEAH, SO LASTLY, WE DO FEEL THAT THIS IS A UNIQUE NICHE THAT CAN BE FILLED BY THE R25 INITIATIVE THAT, IT ENHANCES THE NIAID PORTFOLIO PROGRAMS TO INCREASE PARTICIPATION OF GROUPS UNDERREPRESENTED ABOUT BIOMEDICAL RESEARCH AND DEVELOP A NUMBER OF EARLY STAGE INVESTIGATORS AT MULTIPLE LEVELS. ONLY INSTITUTIONAL PROGRAMS THAT EXPOSES BOTH UNDERGRADUATES AND HEALTH PROFESSIONAL STUDENTS FROM UNDERREPRESENTED BACKGROUNDS ARE ELIGIBLE FOR THESE RESEARCH TRAINING OPPORTUNITIES. AND IT PROVIDES INSTITUTIONAL SUPPORT FOR RESEARCH DEVELOPMENT TRAINING WHICH WILL ULTIMATELY INCREASE THE RETENTION AND NUMBER OF SUCCESSFUL INDEPENDENT RESEARCHES FROM UNDERREPRESENTED GROUPS. AND THIS IS MY LAST SLIDE. I'M HAPPY TO TAKE QUESTIONS. >> I HAVE A QUESTION, THIS IS ANNA [INDISCERNIBLE]. I HAVE A QUESTION ABOUT POTENTIAL OVERLAPPING OR ACTUALLY COMPLEMENTATION WITH EXISTING PREP PROGRAMS OR EXISTING T32S IN SPECIFIC TUITIONS HOW DO YOU ENVISION HAVING THESE PROGRAMS LIKE CUT OFF JOIN TOGETHER AND TRYING TO AVOID OVERLAPPING. >> SURE, AND WE HAVE HAD A REGULAR R25 PROGRAM IN EXISTENCE FOR QUITE A WHILE, IT SCWUOF THE HASN'T BEEN TARGETED TO UNDERREPRESENTED MINORITIES. AND REALLY THE OVERLAP IS JUST SIMPLY THAT, THAT YOU CAN'T PROPOSE THE SAME TRAINING ACTIVITY IN BOTH AWARDS. BUT YOU CAN CERTAINLY COMPLEMENT THAT. FOR ANYONE WHO'S LED A T32 FOR EXAMPLE, YOU KNOW THERE ARE A NUMBER OF THINGS THAT CAN'T COUNT UNDER THE RESEARCH TRAINING, THE DEFINITION OF RESEARCH TRAINING ACTIVITIES AND THEREFORE CAN'T BE PAID FOR BY THE T32. ALL THOSE ACTIVITIES YOU CAN'T PAY FOR WITH THE T32 CAN BE PAID FOR UNDER THE R25. I CAN'T EVEN THINK OF A SINGLE RESEARCH TRAINING ACTIVITY THAT WOULD NOT BE ALLOWABLE UNDER THE R25. SO IN THE ABSENCE OF DIRECT OVERLAP, YOU CAN DOVETAIL THE PROGRAMS AS MUCH AS POSSIBLE. >> THANK YOU. >> ANY OTHER QUESTIONS FOR MATTHEW. OKAY. SO I THINK YOU WILL HAVE TO ENTER YOUR VOTES ON CLEARING THIS CONCEPT FOR INITIATIVE DEVELOPMENT FOR NIAID AND THE ELECTRONIC COUNCIL BOOK. AND I THINK WE WOULD LIKE TO MOVE ON WITH OUR PROGRAM AND THE NEXT PRESENTER IS PUNAM MATHUR WITH THE OFFICE OF GENOMICS AND APPLIED TECHNOLOGIES, SHE WILL PRESENT THE NQ22 CENTERS FOR RESEARCH ON STRUCTURAL BIOLOGY AND INFECT YOWZ DISEASES. >> GOOD AFTERNOON, CAN EVERYONE HEAR ME. >> YES. >> SO GOOD AFTERNOON MY NAME IS PUNAM MATHUR, AND I WILL PRESENT TO YOU THE CENTERS FOR RESEARCH OF STRUCTURAL BIOLOGY OR INFECT YOWZ DISEASES OR CRSTAL-ID, SO BEFORE I START I WOULD LIKE TO SAY THANK YOU FOR THE OPPORTUNITY TODAY AND I WOULD LIKE TO THANK DR. GREENBURG AND DR. PATHWAY GIVES TELEWITH ME AND THEIR HELPFUL FEEDBACK. THE CRSTAL-ID IS A PROGRAM HERE AT NIAID. SO, CRSTAL-ID THOSE ARE TO PROVIDE A GENE TO STRUCTURE PIPELINE TO DETERMINE 3D STRUCTURES FOR PRIORITY HUMAN POGHT O GENS TO ADDRESS RESEARCH GAPS USING STATE-OF-THE-ART STRUCTURAL BIOLOGY METHODS THAT INCLUDE CRYSTALLOGRAPH SKPE BAKUGAN MASS SPECTROSCOPY, CRYOEM AND COMPUTATIONAL MODELS TO CHARACTERIZE MOLECULAR AND BIOCHEMICAL FUNCTIONS OF SELECTED PROTEIN TARGETS THAT ADDRESS NIAID PRIORITIES TO PERM FORM STRUCTURE GUIDED VACCINE DESIGN AND DRUG DISCOVERYY ON VACCINE AND THERAPEUTIC CANDIDATES, TO RESPOND TO CERTAINLY--CERTAINLY MERGING INFECTIOUS DISEASES, THREATS AND PROGRAMMATIC PRIORITIES, THESE ARE MADE FREELY AVAILABLE TO THE SCIENTIFIC COMMUNE INCLUDING 3D STRUCTURE INFORMATION AND REAGENTS. TO GIVE YOU A BRIEF HISTORY OF THE PROGRAM, IT WAS START INDEED 2007. TWO CENTERS WERE AAWARDED TO GSCID AND HEADQUARTERED AT THE CENTER ARE IF INFECTIOUS DISEASE RESEARCH, NOW PART OF THE SEATTLE CHILDREN'S RESEARCH HOSPITAL. BOTH CENTERS ARE A CONSORTIA OF MULTIPLE LAPS THAT ARE HIGHLY INTERDISCIPLINEAR SKPE BAKUGAN COLLABORATIVE, BOTH WITHIN THE CENTER AND WITH EACH OTHER. OVER THE COURSE OF THE PAST 13 YEARS, BOTH CENTERS HAVE EVOLVED FROM THEIR ORIGINAL MANDATE WHILE CONTINUING TO OFFER A ROBUST PIPELINE DETERMINE NATION SERVICES. YOU CAN SEE THAT THEY'RE--THEY HAVE EVOLVED AND MATURED FROM TECHNOLOGY DEVELOPMENT, CAPACITY BUILDING AND STRUCTURES SOLVED TO FUNCTIONAL CHARACTERIZATION OF TARGETS, TAKING ON MORE CHALLENGING TARGETS AND RESPONDING TO INFEBLGHT YOWZ DISEASE THREATS. TO GIVE YOU A QUICK SENSE OF THE IMPACT OF THIS PROGRAM, SINCE THEIR INCEPTION, THE CENTERS HAVE PROCESSED REQUESTS IF ARE MORE THAN 28,000 REQUESTS OF WHICH 46% OF THEIR REQUESTS ON AVERAGE HAVE COME FROM THE SCIENTIFIC COMMUNITY IN THE CURRENT PHASE, THE NUMBER OF REQUESTS THAT THEY GET FROM THE COMMUNITY HAS JUMPED UP TO NEARLY 70%, OF THESE REQUESTS THAT HAVE COME IN, MORE THAN 2700 STRUCTURES HAVE BEEN DEPOSITED IN THE PTB, THAT HAS RESULT INDEED OVER 380 PUBLICATIONS WITH OVER 6000 CITATIONS. THEY HAVE ALSO MADE AVAILABLE THEIR EXPRESSION CLONES AND PURIFIED PROTEINS TO THE SCIENTIFIC COMMUNITY. THEY HAVE HAD SEVERAL HIGH PROFILE PUBLICATIONS INCLUDING THE COVERS ON SOME OF THE JOURNALS THAT YOU CAN SEE HERE, I WOULD LIKE TO POINT OUT THE SPECIAL ISSUE OF PROTEIN SCIENCE--WHOOPS, I AM SO SORRY. --ON PROTEIN SCIENCE HERE. THIS WAS A SPECIAL ISSUE ON ANTIMICROBIAL RESISTANCE AND THE 2 CENTERS COLLECTIVELY CONTRIBUTED 10 ARTICLES TO THIS SPECIAL ISSUE THAT WAS PUBLISHED LAST MARCH. THE CENTERS HAVE A GLOBAL OUTREACH FOR SURFACES THAT ARE REQUESTED BY THE SCIENTIFIC COMMUNITIES, THEY ALSO PARTNER WITH PUBLIC-PRIVATE PARTNERSHIPS TO FURTHER MANY CANDIDATES TO ASSESS WHETHER, YOU KNOW THEY MAKE FOR A GOOD THERAPEUTIC AND VACCINE TARGETS. SO THERE ARE MANY ACCOMPLISHMENTS FROM THE 2 CENTERS, BUT CENTRAL TO THIS PASTIARY'S EFFORT, FROM BOTH CENTERS HAVE BEEN THEIR RESPONSE TO THE COVID-19 PANDEMIC. SINCE LAST JANUARY, THE CENTERS AS PART OF THEIR MANDATE HAVE PIVOTED AND DEDICATED THEIR RESOURCES, TO ADDRESS STRUCTURAL BIOLOGY, DRUG DISCOVERIES, VACCINE DEVELOPMENT AND DIAGNOSTICS TO PROVIDE VITAL STRUCTURAL INFORMATION TO SUPPORT GLOBAL--CENTERINGS HAVE COLLECTIVELY SOLVED OVER 80 STRUCTURES THAT HAVE BEEN DEPOSITED IN THE PDB THAT ACOULD YOU WANT FOR OVER 15% OF ALL SARS-COV-2 STRUCTURES THAT ARE IN PDB. FURTHER BOTH CENTERS HAVE ALSO PROVIDED EXPRESSION PLAZ MIDS MITTS TO PEA FOR GRIEWKS INCLUDING FULL LENGTH SPIKE PROTEIN FROM CORONAVIRUSS AND AS MUCH NEEDED REAGENTS FOR THE SARS-COV-2 COMMUNITY. ARK DITIONALLY A PUBLIC WEBSITE, CORONAVIRUS 3D GEPPED BY THE STRUCTURAL GENOMIC CENTER, THAT INTEGRATES PUBLIC INFORMATION ON THE MUTATIONS WITH THE DATA ON PROTEIN STRUCTURE SYSTEM AVAILABLE AS A RESOURCE TO THE SCIENTIFIC COMMUNITY. SEE THIS A BUSY SLIDE. I APOLOGIZE BUT MOVING FROM BASIC TO TRANSLATIONAL RESEARCH, WORK DONE BY BOTH CENTERS HAS RESULTED IN MOVING MULTIPLE THERAPEUTIC AND VACCINE CANDIDATES INTO THE CLINICAL PIPELINE. FIRST HERE ON THE LEFT, S309 IS A POTENT NONE O CLONAL NEUTRALIZING ANTIBODY, THAT WAS CHARACTERIZED IN COLLABORATION WITH [INDISCERNIBLE] MANUFACTURING TECHNOLOGY AND ENTERED THE CLASS AND EVALUATING NOW IN PHASE 3 CLINICAL TRIALS. THE STRUCTURAL BASIS OF MECHANISM OF S309 MEDIATED NEUTRALIZATION WAS ELUCIDATED USING KRIST O EM TO DEMONSTRATE THAT THE COMPLEX IS FORMED BETWEEN THE ANTIBODY AND THE PREFUSION TRIEMER OF SARS-COVOF 2 SPIKE. NEXT THE POTENTIAL OF BINDING PROTEINS AS ANTIVIRALS, THESE MINIBINDER PROTEINS WERE COMPUTATIONALLY DESIGNED AND TARGETED THE INTERACTION BETWEEN THE SPIKE DEREPRESENTOR DOMAIN AND THE ACE 2 HUMAN RECEPTOR. HIGH RESOLUTION OF THE PROTEIN BINDERS IN COMPLEX WITH THE SARS-COV-2 SPIKE WERE ALSO DETERMINE BIDE KRIST O EM, TO SHOW THAT THE COMPUTATIONAL MODELS WERE NEARLY IDENTICAL TO THE STRUCTURES THAT WERE SOLVED. THESE AND SPECIFICITY OF THIS DESIGNED APPROACH ALLOWS FOR MULTIPLE COMBINATIONS THAT TARGET DIFFERENT REGIONS OF THE RECEPTOR BINDING DOMAIN, THUS PRODUCING THE LIKELIHOOD OF ESCAPE MUTANTS. FIFTY-TWO FINALLY AS ARE THE PART OF A COLLABORATION WITH PFIZER, THE STRUCTURAL DPE GOMMIC CENTERS CONTRIBUTED TO A COMPOUND THAT WAS DEVELOPED AT PFIZER AND IT'S A PRECLINICAL LEAD COMPOUND THAT TARGETS THE MAIN SARS-COV-2 PROTEASE, 3 CL PRO. BOTH THE PFIZER COMPOUND AND REMDESIVIR POTENTLY INHIBIT SARS-COV-2 HUMAN EPITHELIAL CELLS THEREBY PROVIDING INVITRO EVIDENCE OF THIS COMPOUND ANN EFFECTIVE ANTIVIRAL AGAINST SARS-COV-2. WORK IS ONGOING AT THE CENTER FOR A NOVEL CLASS OF BROAD SPECTRUM PAN-CORONAVIRUS INHIBITORS. CAN YOU SEE HERE, THE CENTERS HAVE ALSO CONTRIBUTED TO THE DEVELOPMENT OF NOVEL VACCINE STRATEGIES SUCH AS STRAWCTURE BASED NANO PARTICLE VACCINES. THESE COMPUTATIONALLY DESIGNED PARTICLES ARE CREATED BY COMBOYNING 2 PROTEIN SUBCOMPONENTS WHICH SELF-ASSEMBLE INTO NANO PARTICLE SCAFFOLDS, FURTHER FUSING A SPECIFIC ANTIGENERATED TO 1 OF THE SUBCOMPONENTS YIELDS NANO PARTICLE THAT CAN DISPLAY UP TO 60 COPIES OF THE ANTIGEN LEADING TO A MORE ROBUST IMMUNE RESPONSE. AS YOU CAN SEE HERE ON THE TOP, THE SARS COV-2 NANO PARTICLE VACCINE HAS BEEN SHOWN TO BE HIGHLY IMMUNOGENIC, ELICITING A ROBUST ANTIBODY REINTONS IN MICE, AND DEMONSTRATES THE RAPID DEVELOPMENT IN RESPONSE TO THE ONGOING COVID-19 PANDEMIC THAT IS POSSIBLE THAT THIS PLATFORM, BOTH THE SARS-COV-2 NANO PARTICLE VACCINE IS RSV VACCINE,URE CURRENTLY IND ENABLING STUDIES AND OUR SCHEDULED TO BEGIN PHASE 1 CLINICAL TRIALS LATER THIS YEAR. THE CENTERS HAVE ALSO COLLABORATE WIDE THE VRC, FOR THE INFLUENZA NANO PARTICLE VACCINE THAT DISPLAYS VARIOUS HAs FROM SEASONAL SUBTYPES. FINALLY THE CENTERS ARE WORKING ON CREATING A VACCINE AGAINST HEPATITIS C, E1 E2 NANO PARTICLE HAS BEEN SUCCESSFULLY DESIGNED AND ASSEMBLED, IMMUNEOLOGICAL CHARACTERIZATION AND CRYOEM OF PURIFIED NANO PARTICLES IN THE SCALE UP FOR PAN ANIMAL STUDIES IS CURRENTLY ONGOING. LASTLY I WOULD ALSO LIKE TO SHOW YOU THE SYNTH TAIS INHIBITOR SHOWN HERE THAT ARE PROMISING ANTIMICROBIAL DRUG TARGETS AGAINST TB, SOME OF THESE TARGETS THAT IS WORK THAT IS DONE IN COLLABORATION WITH THE STRUCTURE GUIDED DISCOVERY COALITION WHICH IS A BILL AND MILL MELINDA GATES FUNDED AND THE CONTROL OF THE STRUCTURAL GENOMIC CENTERS IS TO ENABLE STRUCTURAL BASE DESIGN BY DETERMINING STRUCTURES OF THESE NEW PROTEINS. WITH THAT, THE PURPOSE AND SCOPE OF CRSTAL-ID, TO DETERMINE 3D STRUCTURES PROTEINS FOR HUMAN PATHOGEN GENERATEDS USING STATE-OF-THE-ART STRUCTSURAL WIMBERLYOLOGY METHODS AND CONTINUE TO ENHANCE THESE SERVICES AND MAKE THEM AVAILABLE TO THE SCIENTIFIC COMMUNITY. THE PROPOSED CHANGES FOR THIS PROGRAM IS TO ENHANCE THE PIPELINE FOR AUTOMATED STRUCTURE PREDICTION AND COMPUTATIONAL MODELING BECAUSE THESE EFFORTS CAN AID IN CRYOEM, STRUCTURE DETERMINE NATION AND TO PROVIDE A MORE INTEGRATED STRUCTURE DETERMINE NATION PIPELINE. TO PROVIDE RESEARCH INFRASTRUCTURE FOR EMERGING INFECT YOWZ DISEASE THREATS AND PANDEMIC PREPARED BUSINESS TO PROVIDE STRUCTURAL BIOLOGY SUPPORT TO ONGOING PROGRAMS SUCH AS THE NEWEL ESTABLISHED CREID NETWORK, CARB-X PROGRAM AND WE WOULD ASK FOR DMID REPRESENTATION ON THE SCIENTIFIC ADVISORY BOARD, I APOLOGIZE. AND AGAIN I WOULD LIKE TO THANK DR. P A TEL AND DR. GREENBERG FOR THEIR FEEDBACK, THEY WERE VERY SUPPORTIST SUPPORT--SUPPORTIVE OF TH E PROGRAM AND RECOMMENDED WE INCREASE VISIBILITY ACROSS THE INFECTIOUS DISEASE RESEARCH COMMUNITY AND EXPAND ON OUTREACH EFFORTS BY THE CENTERS TO MAKE THE WEBSITES MORE USER FRIENDLY AND TO HARMONIZE THE CENTER WEBSITES WITH RESPECT TO INFORMATION ON SUBMITTING TARGET REQUESTS. SO WITH THAT I WILL LEAVE THIS SLIDE UP AND TAKE ANY QUESTIONS THAT YOU MAY HAVE. THANK YOU. >> EXCUSE ME, THIS IS KEN, I HAVE A TECHNICAL QUESTION, 1 OF THE CURRENTLY FUNDED CENTERS AT MY INSTITUTION, I WONDER IF I'M IN CONFLICT IN VOTING ON THIS INITIATIVE? DOES THAT MATTER IN THE CASE OF INITIATIVES? >> BARBARA OR LILLIAN DO YOU HAVE A COMMENT ON THAT. >> I DON'T THINK WE ORDINARILY-- >> BECAUSE IT'S AN OPEN SESSION, I THINK WE DON'T GENERALLY DEAL WITH THE CONFLICT ISSUES IF YOU FEEL STRONGLY, YOU CAN ABSTAIN FROM VOTING BUT WE DON'T HAVE AN OFFICIAL CONFLICT. >> OKAY, THANK YOU. >> I'LL JUST COMMENT THAT I GOT A CHANCE TO REVIEW THIS. THANK YOU SO MUCH. I'M VERY EXCITED BY IT, I WILL POINT OUT THAT THE NAME CRSTAL-ID IS VERY COOL, I THINK HAVING GOOD ACRONYMS CAN BE HELPFUL AND MY 1 COMMENT WAS JUST, YOU KNOW TO THINK ABOUT THE COMMUNICATION PIECE TO MAKE THOSE AWARE OF THIS POSSIBILITY THAT REALLY MIGHT BENEFIT FROM USING IT, WHETHER THEY'RE NIH FUNDED INVESTIGATORS OR NOT, AND I THINK THAT'S VERY HARD. I DON'T KNOW EXACTLY HOW TO DO IT, IT'S SORT OF COMMUNICATIONS AND MARKETING, BUT I BET THERE ARE PEOPLE OUT THERE EVEN NIAID FUNDED INVESTIGATORS WHO GET BENEFIT SO ANY SORT OF CONNECTION, COMMUNICATION OR MATCH MAKING WOULD REALLY BE WELCOMED. I DID HAVE A CHANCE TO POKE AROUND ON THE WEBSITES AND I COULD FIND MOST OF THE THINGS THAT I WAS LOOKING FOR ONCE I GOT THERE, SO I THINK MAYBE IT'S MORE LEADING PEOPLE TO THE WEBSITES THAN PERFECTING THE WEBSITES. THAT WOULD BE HELPFUL. >> THANK YOU. >> I ALSO THOUGHT IT WAS A GREAT RESOURCE AND I WOULD SAY JUST LIKE ROBIN TO WORK EVEN HARDER TO MAKE SURE THAT AS MANY PEOPLE AS POSSIBLE WHO MIGHT BENEFIT FROM THIS, ARE AWARE OF IT. I CERTAINLY--AFTER I JUST INFORMALLY ASKED A COUPLE PEOPLE WHO ARE TRYING TO GET STRUCTURE THINGS DONE WHETHER THEY HAD EVER HEARD OF THIS AND FOUND THAT THESE ARE PRETTY SERIOUS SCIENTISTS SAID WHAT ARE YOU TALKING ABOUT. SO IT'S ALWAYS HARD TO DO COMMUNICATION AND 1 CAN ALWAYS DO IT BETTER. >> CERTAINLY. >> I WOULD TEND TO--THE NAME IS A COOL NAME BUT IT SUGGESTS A PREFERENCE FOR CRYSTALLOGRAPHY OVER KRIST O EM AND IT SEEMS TO ME FROM WHAT I KNOW ABOUT IT, FROM THE A DISTANCE, THE FIELD IS MOVING FORWARDS CRYORAPID LOAMACYY AND I WONDER OF THE STRUCTURES THAT HAVE BEEN SOLVED HOW MANY WERE SOLVED BY CRYOVERSUS CRYSTALLING ON GRAFY AND IS THERE A MOVE IN THAT DIRECTION? >> THERE IS A MOVE IN THAT DIRECTION BUT SOLVING STRUCTURALLY ARES BY CRYOEM IS EXPENSIVE SO BETWEEN THE 2 CENTERS THEY HAVE SOLVED OVER20 STRUCTURALLY ARES BY CRYOEM THAT MIGHT BE SLIGHTLY CONSERVATIVE BUT THE MAJORITY OF THE STRUCTURES ARE SOLVED BY X-RAY CRYSTALLOGRAPHY. >> ARE THE CENTERS EQUIPPED WITH THE APPROPRIATE INSTRUMENTATION AND THE CRYOIS MANY STRIEWPTS ARE SCATTERED AROUND. >> THEY ARE THE UNIVERSITY OF WASHINGTON AND THEN AT PURDUE AS WELL AS WASHINGTON AT ST. LOUIS, WASH-U HAS CRYOEM FACILITY. >> THANK YOU. >> SO THIS IS KENNY AND I WOULD LIKE TO ADD IN ADDITION TO PROVIDING STRUCTURES, THEY ALSO ARE EXPRESSING A LOT OF THE PROTEINS AND SO THERE ARE PRODUCTS THAT ARE AVAILABLE FROM THIS INITIATIVE. >> YES. >> OKAY, SO PLEASE DOCUMENT YOUR APPROVAL OR OTHERWISE IN THE ELECTRONIC COUNCIL BOOK AND THANK YOU PUNAM. WE WILL MOVE ON TO THE NEXT PRESENTATION WHICH IS AN IMPORTANT PART OF OUR CLINAL TRIALS INFRASTRUCTURE, THE DMIDCLINICAL MATERIALS SERVICES PRESENTED BY JACE, AREGA, WHO IS THE DEPUTY DIRECTOR OF OFFICE OF REGULATORY AFFAIRS OF DMID. AND I WILL JUST TELL THE CONFERENCE GROUP, THAT I HAVE TO TAKE AN IMPORTANT CALL ON THE THREAT OF VARIANTS SO I MIGHT STEP OUT FOR A BRIEF PERIOD OF TIME AND TURN THE STEERING WHEEL OVER TO CHRISTINA CASSETTI, SO THAT'S WHERE I AM YOU WILL HEAR HER VOICE LATER BUT I'M HERE UNTIL 2:00 O'CLOCK. THANKS. GO AHJACE. >> THANK YOU, GOOD AFTERNOON, CAN YOU HEAR ME? >> YES. >> OKAY, SO I'M THE DEPUTY DIRECTOR FOR THE OFFICE OF REGULATORY AFFAIRS AND I HAVE THE DISTINGUISHED PLEASURE OF PRESENTING TO PROTOCOLS TODAY. SORRY ABOUT THAT. THIS CONCEPT PROVIDES FOR THE MANAGEMENT AND OPERATION OF A GOOD MANUFACTURING PRACTICE COMPLIANT FACILITY OR DMID SPONSORED CLINICAL TRIAL IN THE U.S. AND ABROAD. BOTH FOR CLINICAL AGENTS AND SPECIMENS AND THIS SERVICES INCLUDE THE RECEIPTS, STORAGE, ALIAISON QUOTING, LABELING, PACKAGES, REPACKAGING, SHIPPING, TESTING, AND FINAL DISPOSITION. AND JUST A LITTLE BIT OF HISTORY ON THIS CONCEPT, THIS IS WHERE--THIS WILL BE THE THIRD RECOMPETE AND IF AWARDED, IT WOULD BE FUNDED THROUGH CONTRACT MECHANISM WHO WE ANTICIPATE 1 AWARD, IT WAS LAST PRESENTED TO COUNCIL IN 2015 AND THE SCOPE AND OBJECTIVES REMAIN THE SAME. SO BECAUSE THIS IS A CORE SERVICE TO THE DMID CLINICAL INFRASTRUCTURE AS EMILY JUST SAID, THE ACCOMPLISHMENTS ARE REALLY THE VOLUME OF EITHER ACTIVITIES DONE OR THINGS PURCHASED SO I'M JUST GOING TO THROW NUMBERS AT YOU, SO NUMBER OF TEST ARTICLES RECEIVED OVER THE LIFE OF THE CONTRACT AND THESE ARE INDIVIDUAL PRODUCTS SO NOT, YOU KNOW 10 VILES OF 1 THING, IT'S THE NUMBER OF INDIVIDUAL PRODUCTS. JUST UNDER 200,000. NUMBER OF TEST ARTICLES SHIPPED, 112,000 AND COUNTING. CLINICAL SPECIMENS RECEIVED JUST OVER 1.3 MILLION. CLINICAL SPECIMEN SHIPPED, A LITTLE BIT OVER 150,000. CLINICAL SPECIMENS DESTROYED, A LITTLE BIT UNDER 40,000. CLINICAL AGENTS PURCHASED RIGHT AT THE HALF MILLION MARK AND EQUIPMENT PURCHASED WE'RE AT THE MILLION DOLLAR MARK AND THESE INCLUDE LIQUID NITROGEN TABS MINUS 80 FREEZERS,-20 FREEDERS, REFRIGERATORS, ET CETERA. SO IF YOU TAKE THOSE NUMBERS AND BREAK THEM OUT FOR 2020 AND THEN OF THE 2020 NUMBERS THOSE THAT WERE RELATED TO COVID, THE NUMBERS ARE QUITE STRIKING, SO TEST ARTICLES RECEIVED AND THESE ARE OVER 83,000 WERE COVID RELATED, AS ARTICLES SHIFT, JUST OVER 77,000 AND JUST ABOUT HALF OF THOSE 35,000 WERE COVID RELATED. CLINICAL SPECIMENS RECEIVED JUST OVER 300,000 AND ALMOST 250,000 OF THOSE COVID RELATED. CLINICAL SPECIMENS SHIPPED JUST OVER 44,000 AND WE REALLY JUST STARTED TESTING OUR COVID RELATED SPECIMEN FOR THE 1S THAT DMID HOLD SO WE HAVE ONLY SHIPPED OUT JUST UNDER 9000. OF THOSE CLINICAL SPECIMENS DESTROYED 500--SORRY--5500 AND NONE OF THEM COVID RELATED BECAUSE AS I JUST SAID WE'VE JUST BARELY STARTED TESTING THOSE. SO I JUST WANTED TO TAKE A MOMENT HERE, I THINK IF YOU WERE ON EARLIER, EMILY MENTIONED THAT DMID WAS--IS PART OF THE MODERNA VACCINE TRIAL, WE WERE ACTUALLY THE I& D HOLDER FOR THE PHASE 1 STUDY AND AS PART OF THAT AND THIS PARTICULAR CONTRACT, THE CHALLENGE BECAME SHIPPING MINUS PRODUCTS TO SITES AND MAKING SURE WE MAINTAIN PROPER STORAGE DURING SHIPMENT AND THEN FOR REMDESIVIR AND BARICITINIB, THESE WERE PART OF OUR COVID-19 TREATMENT TRIAL, ACTT-1 AND 2, AND THE STRUGGLES HERE WERE THAT WE HAD OVER 60 SITES, SOME GRAGZAL 1S INCLUDED AND TRYING TO GET PRODUCT TO SITES. THIS WAS LEAKED EARLY MARCH WHEN SPLIETS WERE BEING SHUT DOWN AND WE DIDN'T QUITE KNOW WHEN THE NEXT PLAIN WOULD BE AVAILABLE. THIS KNOW CO TACT WE WERE ABLE TO DO IT, WE GOT THE STUDIES DONE AND THE DATA FROM THESE TRIALS, STUDIES WERE USED TO SUPPORT AS EMILY MNGZED EARLIER, EITHER EMERGENCY USE AUTHORIZATION OR LICENSURE CASE IN THE CASE OF REMDESIVIR. SO THIS CONTRAST ALSO SUPPORTS SMALL SCALE MANUFACTURING, MOSTLY [INDISCERNIBLE] OR OVERINCAP SUEALATIONS OR PLACEBOS. SO FOR EXAMPLE, THE BUFFERED SALINE, AND ANYTHING THAT WE MANUFACTURE UNDER THIS CONTRACT THEN HAS TO GO ON TO A STBILITY PROGRAM UNTIL THE LAST SUBJECT AND DOSED SO THIS CONTRAST ALSO SUPPORTS SUCH STABILITY TESTING. AT THIS TIME I WOULD LIKE TO THANK DR. P A TEL AND COLONEL TIGER, THEY WERE THE PRIMARY COUNCIL REVIEWERS AND THEY DIDN'T HAVE ANY QUESTIONS, BUT I WOULD LIKE TO OPEN IT NOW TO THEM OR ANY OTHER COUNCIL MEMBERS IF THERE ARE ANY QUESTIONS. >> YEAH TO, ME THIS SEEMED VERY STRAIGHT FORWARD AND SOMETHING THAT HAS BEEN TREMENDOUSLY HELPFUL ESPECIALLY AS EXEMPLIFIED IN SARS-COV-2 TIMES SO MY SUGGESTION IS THAT IT MOVE FORWARD. >> YEAH, HIGH, THIS IS STEWART [INDISCERNIBLE] AND IT IS VERY STRAIGHT FORWARD AND AGREE THIS SHOULD CONTINUE TO MOVE FORWARD. >> OKAY, SO THAT JAE'S FIRST CONCEPT AND I THINK SHE HAS ANOTHER PRESENTATION. SO PLEASE RECORD YOUR VOTES IN THE NEXT COUNCIL BOOKS AND THE NEXT PRESENTATION BY JAE IS THE DMID REGULATORY AFFAIRS SUPPORT. THIS IS THE SECOND CONCEPT, FY22. THIS IS THE REGULATORY AFFAIRS SUPPORT AND LIKE THE PREVIOUS 1 THIS CONCEPT PROVIDES CORE SERVICES TO THE DMID CLINICAL INFRASTRUCTURE. NO, I CAN'T MOVE THE SLIDES. >> CLICK ON IT AGAIN. WITH YOUR MOUSE. >> OKAY, PERFECT. OKAY, SO THIS CONCEPT PROVIDES A BROAD CHANGE OF REGULATORY ACTIVITIES IN SUPPORT OF DMID SPONSORED CLINICAL AND NONCLINICAL RESEARCH ACTIVITIES. IN THESE SERVICES INCLUDE THE PREPARATION, REVIEW AND SUBMISSION OF DOCUMENTS FOR REGULATORY FILING AND MOSTLY TO THE FDA. TECHNICAL WRITING AND REPORTS PREPARATION. THE MAINTENANCE AND OPERATION OF A WEB BASED INFORMATION SYSTEM AND THE SYSTEM IS USED TO TRACK REGULATORY ACTIFORTS AND FOR ARCHIVING OF OUR ELECTRONIC SUBMISSIONS. IT PROVIDES LOGISTICS SUPPORTS INCLUDING MEETINGS, PARTICULARLY WHEN WE MEET WITH THE FDA. IT PROVIDES TRAINING TO INTERNAL DMID STAKEHOLDERS AND THEY PROVIDE CONSULTANTS AND AUDITORS AND OTHER EXPERTISE WHEN EITHER DMID HAS LIMITED RESOURCES OR WE DON'T HAVE THOSE RESOURCES AT ALL. SO A LITTLE BIT OF HISTORY, AGAIN, THIS IS THE THIRD RECOMPETE, IF AWARDED IT WILL BE FUNDED THROUGH GRANT MECHANISM, WE ANTICIPATE 1 AWARD, IT WAS LAST PRESENTED TO COUNCIL IN 2015 AND THE SCOPE AND OBJECTIVES REALLY REMAIN THE SAME. SO AGAIN THE ACCOMPLISHMENTS UNDER THIS CONTRACT ARE REALLY NUMBERS. SO THROWING NUMBERS AT YOU AGAIN. TOTAL NUMBER OF SUBMISSIONS OVER THE LIFE OF THE CURRENT CONTRACT IS 2300, A LITTLE BIT OVER. THE TOTAL NUMBER OF INITIAL NEW INVESTIGATIONAL DRUG APPLICATIONS OVER A 4 YEAR PERIOD OF 53 WHICH AVERAGES ABOUT 10 PER YEAR. TOTAL ACTIVE FDA APPLICATION SYSTEM 107 AND THAT NUMBER HAS CONSISTENTLY REMAINED ABOUT A HUNDRED OR SO FOR THE ENTIRE--FOR EACH OPTION YEAR OF THE CONTRACT. THEN IF YOU TAKE THE TOTAL NUMBER OF SUBMISSIONS BROKEN BY CONTRACT YEAR, WE AFVAJ WELL OVER 400 UP TO 500 IN SOME CASES FOR EACH OPTION YEAR, THAT 207, IS LOW BECAUSE THAT WAS OUR FIRST YEAR AND THE CONTACT WAS AWARDED MIDDLE YEAR, I THINK JUNE OF THAT YEAR. SO, WE AVERAGE BETWEEN 400 TO 500 SUBMISSIONS EACH YEAR. SO SOME OTHER ACCOMPLISHMENT, ABOUT 3 YEARS AGO, FDA MANDATED THAT COMPANIES NO LONGER SUBMIT APPLICATIONS AND SUBSEQUENT SUBMISSION TOSS THEM IN PAPER FORMAT, THAT IT HAD TO BE ELECTRONICALLY DONE, NOT ONLY ELECTRONICALLY BUT IN A PARTICULAR FORMAT, THE ELECTRONIC COMMON TECHNICAL COMMENT, ECTD FORMAT, THE DMID WORKED WITH THE CURRENT CONTRACTOR TO START THE PROCESS OF CONVERTING FROM PAPER TO ELECTRONIC SUBMISSION. WE WERE ABLE TO ACCOMPLISH IT AHEAD OF SCHEDULE, WE BEAT THE FDA TIMELINE WELL IN ADVANCE OF WHEN WE HAD TO DO IT. WE WERE ALSO SUCCESSFULLY ABLE TO LAUNCH A VALIDATED WEB BASED REGULATORY INFORMATION SYSTEM AND THAT SYSTEM NOW HOUSES ALL OF THOSE ELECTRONIC SUBMISSION THAT WE'RE DOING. WE'VE BEEN ABLE TO ADAPT TO UNUSUAL INCREASES IN WORK LOAD REALLY WITHOUT ANY ISSUES, PARTICULARLY IN THE LAST YEAR HAVING TO GET THE COVID STUDIES UP AND RUNNING WAS NO SMALL FEAT. WE WERE ABLE TO DO THAT BECAUSE WE WERE TRYING TO PUT PROCESSES IN PLACE WHILE TRYING TO GET THOSE STUDIES UP AND RUNNING. SO AT THIS TIME I WOULD LIKE TO THANK DR. LEMON AND DR. FINEBERG, THEY WERE THE PRIMARY REVIEWERS THEY DID HAVE QUESTIONS ABOUT THE FUNDING MECHANISM AND HOPEFULLY PREVIOUS SLIDE CLARIFIED THAT IF AWARDED THIS SLIDE [INDISCERNIBLE] CONTRACT AND THERE WERE QUESTIONS ABOUT THE SCOPE OF THIS. I WANTED TO POINT OUT THAT THIS IS REALLY FOR INTERNAL DMID STAKEHOLDERS, FOR STUDIES THAT ARE DMID SPONSORED, WHERE DMID IS THE ID HOLDER SO NOT REALLY AVAILABLE TO OUR EXTERNAL PARTNERS BUT I CAN TAKE QUESTIONS ON THAT IF THERE ARE MORE. YEAH IS NOW WE JUST OPEN IT UP TO ANYBODY WHO HAS ANY QUESTIONS. THANK YOU. >> THANK YOU FOR RESPONDING TO MY E-MAIL LAST WEEK, EXPW IT'S TRULY IMPRESSIVE WHAT THIS HAS ACCOMPLISHED AND THAT SEEMSENTIOUS SENTIAL TO WHAT YOU'RE DOING. THE PROOF IS WHAT YOU'VE DONE IN TERMS OF THE MODERNA VACCINE AND THIS WAS AN IMPORTANT PART OF GETTING MOVING THIS FORWARD, YOUR PRESENTATION TODAY IS WHETHER THE SYSTEMS HAVE YOU IN PLACE ARE SUFFICIENTLY ROBUST, IF THEY WERE DISRUPTED BY ANY IMPACT ON THE [INDISCERNIBLE] OR ANY OTHER--WE'VE SEEN A LOST OF DISASTERS IN THE PAST YEAR OR 2. I WOULD HOPE THAT YOU HAVE A SYSTEM THAT'S REALLY ROBUST AND COULD RECOVER FROM ANY KIND OF DISRUPTION, WEB DISRUPTION OR DISRUPTION AT THE SITE OF THE CONTRACT? WHETHER YOU [INDISCERNIBLE] STORAGE, OF RECORDS, SOFTWARE DATABASES AND SO FORTH, I'M SURE YOU DO BUT-- >> THANK YOU FOR THE QUESTION. IT'S A REALLY GOOD QUESTION AND WE ACTUALLY, WE DO HAVE A ROBUST SYSTEM, WEAVER HAD IT TESTED, WE LOST DATA, LET'S SEE ABOUT 2 YEARS AGO AND WE HAD TO GO TO OUR OFFSITE STORAGE FACILITY AND TRY TO RETRIEVE WHAT WAS BACKED UP. THERE WAS A SMALL--THERE WAS MAYBE A MONTH OR 2 OF DATA WE COULDN'T RETRIEVE, IT WAS DAT FRANCIS COLLINS THE VERY BEGINNING OF ACTUALLY THE FIRST AWARD. SO MAYBE 15 YEARS AGO BUT WE'VE SINCE--IT WAS A LEARNING EXPERIENCE FOR ME, WE'VE SINCE PUT BACK UP TO THE BACK UP SO THAT WE DON'T EVER LOSE ANYTHING. >> EXCELLENT. THANK YOU. >> YOU'RE WELCOME. >> I HAVE A QUICK QUESTION ABOUT HOW COMPETITIVE IS THIS CONTRACT? IS THIS SOMETHING THAT NORMALLY IS AWARDED TO THE SAME PEOPLE? IS THIS ALMOST INTERNAL OR DO YOU SEE A LOT OF DIVERSE GROUPS AMRIING TO ACTUALLY TAKE OVER THIS? YOU KNOW MAYBE I MISSED IT BUT, IT WASN'T CLEAR TO ME THIS IS ALMOST LIKE AN INTERNAL APPROVAL OF CONTINUING SOMETHING THAT HAS BEEN HISTORICALLY THE SAME PEOPLE OR IF YOU SEE IN DIFFERENT PEOPLE FROM OUTSIDE COME IN AND TRYING TO COMPETE FOR THESE. >> GOOD QUESTION, THANK YOU. SO ACTUALLY IT'S OPEN. IT WOULD BE--IT WILL BE POSTED TO THE PUBLIC, IT'S OPEN 2 ANYBODY. SO IT SHOULD BE COMPETITIVE. HAVING SAID THAT, THE LAST 2 RECOMPETES HAVE BEEN HELD BY THE SAME CONTRACTOR. SO I WILL SAY THAT IT WILL BE DIFFICULT--THERE ARE INTERNAL WORKINGS AT OBVIOUSLY THE CURRENT CONTRACTOR IS MORE PRIVY TO THAN ANYBODY ELSE WE WOULD ARK PLIE BUT WE WOULDN'T DISCOUNT NEW PEOPLE FROM COMING IN. WE'RE OPEN TO ANYBODY APPLYING. >> I GUESS THEY'RE DOING A GOOD JOB BECAUSE THEY KEEP GETTING IT, THAT'S GOOD. >> YES, WE ARE VERY HAPPY WITH THEM IF I CAN SAY THAT. >> ANY OTHER QUESTIONS OR DO WE HAVE ANY COMMENTS FROM MARK FINEBERG? >> NO, THANK YOU. OBVIOUSLY THIS AN IMPORTANT PROGRAM AND I SUPPORT ITS CONTINUATION AND HAVE PROVIDED FEEDBACK AS JACE INDICATED AND I THINK SHE ADDRESSED MY QUESTIONS AS WELL. >> GREAT. THANK YOU. OKAY. ANY OTHER LAST MINUTE QUESTIONS? >> THANK YOU. >> BEFORE WE MOVE ON TO THE NEXT PRESENTATION, THANK YOU JACE. >> THANK YOU. >> OKAY, WHILE YOU ENTER THE VOTES I WILL INTRODUCE THE NEXT SPEAKER WHO IS RODOLFO ALARCON FROM THE IMMUNOLOGY BRANCH AND HE WILL PRESENT FUNDAMENTAL VIROLOGY FOCUSED RESEARCH TO UNDERSTAND THE EMERGING THREAT OF BUNYAVIRUS INFECTIONS. >> THANK YOU, CAN YOU HEAR ME. >> YES. >> AS MENTIONED I'M A PROGRAM OFFICER IN THE VIROLOGY BRANCH AND IT'S MY PLEASURE TO PRESENT AN OVERVIEW OF THE CONCEPT BUNYAVIRUS, SO BY PROMOTING VIRAL EMERGENCE BY FOCUSING ON 3 GENERAL AREAS, VIRAL ECOLOGY AND IMMUNE RESPONSES TO INFECTIONS. SO PREVIOUS EXPERIENCE FROM RECENT OUTBREAKS SHOW THAT A RAPID NIAID RESPONSE WAS BASED ON YEARS OF PRIOR RESEARCH AND VIROLOGY AND THEN DEVELOPMENT OF POSSIBILITY COUNTERMEASURES. LESSONS LEARNED FROM LAST DECADES EBEIL IS AND ZIKA OUTBREAKS HELP TO FRAME THESE OBJECTIVES LAID OUT IN THE 2017 TRANSLATIONAL RESEARCH STIGIC PLAN IN WHICH 1 PRIORITY WAS TO RESPOND RAPIDLY TO EMERGING AND REEMERGING INFECT YOIS DISEASES THAT COULD OCCUR PERIODIC LOAMACYY AND UNEXPECTEDLY. THIS CONCEPT IS RESPONSIVE TO THE STRATEGIC PLANS BASIC SCIENCE RESEARCH OBJECTIVES AS BUNYAVIRUSES HAVE THE POTENTIAL FOR EXPECTATIONS MERGE ENSEL WHICH COULD RESULT IN GLOBAL OUTBREAKS. ALSO IT ALIGNS WELL WITH THE OVERHAUL GOALS WITH THE NIH RESEARCH STRAY JECTORY STIGIC PLAN AS MANY BUNYAVIRUSES ARE TRANSMITTED BY TICKS. LET'S GO BACK. SO THE RATIONAL FOR THIS CONCEPT IS 3 FOLD. FIRST IT FILLS THE GAP IN BASIC SCIENCE RESEARCH NEEDED TO ADDRESS A VERY LARGE DIVERSE AND IMPORTANT GROUP OF UNDER RESEARCH VECTOR BORNE VIRAL PATHOGENS. SECOND A TARGETED SET ASIDE RO1 FUNDING MECHANISM WOULD PROMOTE FUNDAMENTAL RESEARCH STUDIES WHICH ARE NOT CURRENTLY BEING ADDRESSED BY THE INVESTIGATOR INITIATED RESEARCH GRANT AS A WHOLE. AND THIRD, IT WILL COMPLEMENT CURRENT PANDEMIC EFFORTS WITHIN NIAID SUCH AS THE TRANSLATIONALLY FOCUSED CREED NETWORK BY FOCUSING ON FUNDING BASIC SCIENCE RESEARCH PROJECTS. THIS IS A NEW CONCEPT WITH A TOTAL SET ASIDE FUNDED OF 5 MILLION. WE ANTICIPATE AWARDING 10-14 GRANTS. >> OKAY, SO WHAT ARE BUNYAI HAVE USS, THEY BELONG TO A LARGER ORDER CALLED BUNYAVIRALES, THE LARGEST GROUP IN THE WORLD, 350 MEMBERS OF WHICH 70 ARE ESTIMATED TO HUMAN PATHOJANUARYS, WHICH ARE THEN CATEGORIZED INTO 5 SEPARATE VIRAL FAMILIES. YOU CAN SEE HERE FROM THE SCHEMATIC, BUNYAVIRUSES ARE SMALL, SPHEREICAL ENVELOPES NEGATIVE SINGLE STRANDED RNA VIRUSES WITH SEGMENTED GENOMES. THE SMALL AND LARGE SEGMENTS, PROTEINS REQUIRE REPLICATION ITSELF MAINLY THE RNA DEPENDENT AND MRNA POLYMERASE AND THE MEDIUM SEGMENT CODES FOR ENVELOPE GLYCO PROTEINS THAT ARE REQUIRED FOR PARTICLE BUDDING AND ENTRY INTO TARGET CELLS. SO IN ADDITION BECAUSE THEY ARE SUGMENTORSHIP SKILLED VIRUSES, YOU CAN GUESS, REASSERTMENT HAS BEEN CALMLY OBSERVED BETWEEN CLOSELY RELATED VIRUSES AND IT'S THOUGHT TO BE A DRIVER OF VIRUS DIVERSITY, SO SUFFICE TO SAY, BUNYAVIRUS BENOAMS CAN HAVE SUBSTANTIAL VARIABILITY ACROSS THE ORDER. SO IN ADDITION TO THIS GENOME VARIATION, BUNYAVIRUSES ARE TRANSMITTED BY A WIDE VARIETY OF VECTORS FROM INSECTS ALL THE WAY TO SMALL RODENTS AND FREQUENT CONTACT WITH THESE VECTORS CAN LEAD TO A NUMBER OF DIFFERENT DISEASE TYPES, THESE TYPES. IN GENERAL, MOST BUNYAVIRUS INFECTIONS ARE ASYMPTOMATIC OR LOW SEVERITY AND SELF-RESOLVING AND THEREFORE THEY GO UNREPORTED. SEVERE INFECTIONS THOUGH CAN RESULT IN A WIDE VARIETY OF DISEASE INCLUDING HEMORRHAGIC FEVER, HEPATITIS, AND ENCEPHALITIS, ALL OF WHICH COULD LEAD TO MULTIPLE ORGAN FAILURE, LIVER DAMAGE, AND UNFORTUNATELY MANY INFECTIONS CAN HAVE HIGH MORTALITY. OF PARTICULAR IMPORTANCE IS SEVERE VALLEY FEVER I HAVE US CAN RESULT IN PERMANENT VISION LOSS AND NEUROLOGICAL ISSUES SUCH AS COGNITIVE IMPAIRMENT. SO TAKEN ALTOGETHER, GIIVE THE LODGER NUMBER OF VIRUSES AND THE TYPE OF VIRUSES WITHIN THE ORDER, THEIR ABILITY TO MUTATE AND READILY REASSORT THE DIVERSE TYPES OF VECTORS THAT CARRY AND TRANSMIT THE VIRUSES, AS WELL AS THE SEVERITY OF THE DISEASE CAUSED BY INFECTIONS, THE CLOSE PROXIMITY OF THE VECTORS TO HUMANS FUTURE EMERGING AND REEMERGING OUTBREAKS OF VIRUS SYSTEM CONSIDERED LIKELY TO CONSIDER AND ARE PUBLIC HEALTH IMPORTANCE. AND IN FACT, IF YOU LOOK AT A MAP, OUTBREAKS BY A VARIETY OF VIRUSES AROUND THE GLOBE HAVE BEEN DOCUMENTED BY THE W. H. O. AND THE CDC IN THE PAST 10 YEARS. WHERE ESSENTIALLY CAN YOU SEE THERE'S BEEN AN OUTBREAK IN EVERY CONTINENT OF THE WORLD AND A VARIOUS OF VIRUSES FROM EVERY FAMILY WITHIN THE ORDER ALSO ARING OUTBREAKS OF CCHS, RED VALLEY FEVER VIRUS AND LOSV I HAVE US AND THEY INDEMMIC TO AFRICA AND THE MIDDLE EAST AND THEY CAN CAUSE INFECTIONS INTO THE THOUSANDS. IN RECOGNITION OF THEIR POTENTIAL TO CAUSE A PUBLIC HEALTH EMERGENCY BOTH THE W. H. O. AND [INDISCERNIBLE] HAVE SELECT BUNYAVIRUSES AS PARTY PATHOGENS FOR RESEARCH AND INTERVENTION DEVELOPMENT. I WOULD ALSO LIKE TO ADD THAT MANY ARE HHS AGENTS AND REQUIRE BSL3 OR 4 CONTAINMENT, THIS CAN ADD REGULATORY COMPLEXITY AND COST TO INSTITUTION AND THE INVESTIGATOR DOING RESEARCH ON THESE VIRUSES, SO A MINOR OBJECTIVE OF THIS CONCEPT IS TO HELP INVESTIGATORS WITH TARGETED FUNDING TO SUPPORT LONG-TERM PROJECTS REQUIRING THESE UNIQUE TYPE OF COSTLY RESOURCES. SO WHAT IS THE NIAID'S APPROACH TO ADDRESSING THESE EMERGING PATHOGENS, COLLEAGUES AT NIAID, INTRAMURAL PUBLISHED AN ARTICLE BACK IN 2018 DETAILING PRINCIPLES BY WHICH THE INSTITUTE CAN RESPOND TO PATHOGENS WITH OUTBREAK OR EPIDEMIC POTENTIAL WHERE 1 GOAL IS TO ESTABLISH A FOUNDATION OF BASIC SCIENCE RESEARCH THAT CAN THEN BE LEVERAGED AS PART OF AN OUTBREAK RESPONSE AND PARTICULARLY THEY HIGHLIGHTED BIOLOGY ISSUE STUDIES PATHOGENESIS AND IMMUNEOLOGICAL STUDIES. THIS CONCEPT ALIGNS WELL WITH THIS APPROACH, IT IS RESPONSE TESTIFY NIAID INTEREST AND BUNYA VIRUSES AS WELL AS CONGRESS AT VIRUSES AND INTO TICK BORN DISEASES INCLUDING OR ADDITIONALLY TO LIME DISEASE, THIS IS' RIMINDER MANY BUIN, YAVIRUSES ARE TRANSMITTED BY TICKS. SO LAST YEAR AT DMID ESTABLISHED THE CENTERS FOR RESEARCH IN EMERGING INFECTIOUS DISEASES, IN WHICH THEY WERE TO FOCUS ON SURVEILLANCE, OUTBREAK PRER VENTION AND OTHER ACTIVITIES IN TRANSLATIONAL RESEARCH SUCH AS RE18th AND DIAGNOSTIC DEVELOPMENT FOR EMERGING VIRUSES INCLUDING THE BUNYAVIRUSES, WE EXPECT KNOWLEDGE GAIN FROM PROJECTS THAT CAN BE FUNDED UNDER THIS CONCEPT, PROVIDE THE FUNDAMENTAL BASES FOR MANY ADVANCE STUDIES BY KREED NETWORK SITES. IN ADDITION LAST YEAR, TO GET A BETTER UNDERSTANDING OF THE CURRENT STATE OF RESEARCH IN THE FIELD, DMID, CLBERATE WITH NIH AS WELL AS SEPI, TO HOST A BASIC SCIENCE FOCUSED BUNYAVIRALES WORKSHOP TO IDENTIFY SCIENTIFIC AND TRANSLATIONAL GAPS IN THE FIELD. THE OTHER REASON WAS TO HELP INENCOURAGE RESEARCH TO PATHOGENS THAT WE BELIEVE HAVE THE POTENTIAL FOR EMERGENCE, THIS INCORPORATES MANY FINDINGS FROM THE MEETING WITH 1 UNDERSCORING THE NEED FOR BASIC SCIENCE RESEARCH TO BE DONE NOW INTO PRIORITY PATHOGENS THAT COULD EMERGE OR REEMERGE IN THE FUTURE. SO I MIGHT ASK, WHAT IS THE STATE OF RESEARCH, WHAT ARE WE DOING NOW IN DMID, AND THE EFFORTS? SO AS YOU CAN SEE, OTHER THAN THE TRAINING PROGRAMS, MOST OF THE EFFORTS ARE TRANSLATIONALLY DIRECTED AND THEY SUPPORT THE DIVISION'S EFFORTS IN PRECLINICAL DEVELOPMENT OR CLINICAL DEVELOPMENT OF POSSIBLE VACCINE CANDIDATES. SO IF YOU LOOK AT THE GRANT PORTFOLIO, WE HAVE 25 ACTIVE GRANTS WITH ONLY 6 THAT ARE FOCUSED ON BASIC SCIENCE RESEARCH, GIVEN THE LARGE NUMBER AND DIVERSITY OF VIRUSES AS I MENTIONED EARLIER, THIS IS A VERY SMALL NUMBER OF GRANTS AND THEY'RE ONLY FOCUS REALLY ON JUST A HANDFUL OF I HAVE HAVE YOU SEENS YOU CAN SEE HERE. THERE ARE MANY OTHER BUIN, YAI HAVE USS FOR WHICH WE HAVE VERITH LITTLE INFORMATION ABOUT ESPECIALLY ABOUT THEIR BASIC I HAVEROLOGY AND PATHOGENESIS AND 1 GOAL IS TO FOSTER NEW RESEARCH INTO THESE VIRUSES. SO A TARGETED--RESEARCH IN THIS NASCENT FIELD AND WE WILL FOCUS ON AGAIN WILL GENERAL TOPICS OF VIRAL ECOLOGY, VIROLOGY IMMUNE RESPONSE TO INFECTIONS. WE WILL ENDEAVOR TO TAKE A PRIORITY AND PROTOTYPE PATHOGEN APPROACH AND LAWN MOWER WE MEAN BY THAT IS WE WILL SEEK TO FUND GRANTS IN ALL 5 FAMILIES OF THE ORDER AND I SHOULD ALSO STATE THAT ACTUAL SPECIFIC PATHOGENS THAT WILL BE STUDIED WILL BE INCLUDED FROM EVERY FAMILY BUT WILL BE DESERMED AT THE TIME WE DRAFT THE RFA, AGAIN THAT WILL BE BASED ON THE [INDISCERNIBLE] IN THE FIELD, AND PARTIES WITHIN THE DMID PORTFOLIOS AND ALL WITH THE GOAL OF INSURING THAT WE ARE FILLING GAPS ACROSS THE ORDER AND FOCUSING ON PATHOGENS THAT CAUSE THE MOST SEVERE DISEASE, MORTALITY AND LONG-TERM DISABILITIES IN SURVIVORS. SOME I HAVE ROLL PATHOGENS OF ANY THOUGH, ARE THE ANDYS VIRUS, HEART LAND VIRUS AND RED VALLEY FEVER VIRUS, HOWEVER, SHINAKO NOTE THAT THE FUNDING DECISIONS ALSO WILL BE MADE ON THE QUALITY OF SCIENCE SUBMITTED, THE REVIEW OUTCOME AND AGAIN THE PROGRAMMATIC NEED. WE DO FORSEE THOUGH THAT POTENTIAL AREAS OF RESEARCH GAPS TO BE ADDRESSED IN PARTICULAR UNDERSTANDING VIRAL ENTRY AND IDENTIFYING ATTACHMENT FACTORS AND RECEPTORS BECAUSE REALLY ONLY FINISH FOR THE JUNTA VIRUS ONLY KNOW RECEPTORS FOR THAT SINGULAR BUNYA, SO THAT'S AN NEEDED AREA OF RESEARCH. AND GIVEN THE CRSPR AND TECHNOLOGY AND LOSS OF FUNCTION SCREENS SEEMS TO BE A NICE TOOL TO IDENTIFY THOSE HOST VIRAL INTERACTIONS. WE WILL ALSO--ARE INTERESTED IN RESEARCH ADDRESSING VIRAL INFECTIONS OF THE CNS, AND AGAIN THE REASON IS BECAUSE WHEN YOU LOOK AT THE LONG-TERM DISABILITIES AND SURVIVORS, MOST OF THEM RESULT BECAUSE OF INFECTIONS AND SEVERE INFECTIONS OF THE CNS AND WE REALLY DON'T KNOW THE MOLECULAR AND CELLULAR BASIS FOR THAT. WE ALSO NEED TO DEVELOP TOOLS TO REALLY UNDERSTAND GENE FUNCTION AND VECTORS ARE IN HUMAN HOSTS, AND 1 OF THOSE TOOLS COULD BE DEVELOPMENT OF GENETIC SYSTEMS, THAT WILL GIVE US UNDERSTANDING OF WHAT THESE GENES ARE DOING BUT ALSO PATHOGENESIS AND OF COURSE IMMUNITY IS ANOTHER AREA OF INTEREST AS WELL. SO I WOULD ALSO LIKE TO SAY, ANOTHER BENEFIT OF THIS CONCEPT IS THAT A SPECIAL EMPHASIS PANEL WILL AID AND REVIEW APPLICATIONS, AS MANY INVESTIGATOR INITIATED GRANT APPLICATIONS DON'TY SEEM TO FAIR WELL IN CHARTER STUDIED SECTIONS. THIS LARGELY RESULTS FROM REVIEWERS NOT APPRECIATING THE NEED TO DEVELOP RESEARCH AND INFORMATION ON SOME VIRUSES THAT MAY HAVE LOW INCIDENCE AND A LOW PREVALENCE OF DISEASE, BUT COULD STILL RESULT IN FULTURE MAJOR OUTBREAKS. I HAD THE PLEASURE AND FUN TIME TO TALK WITH DR. [INDISCERNIBLE] AND DR. [INDISCERNIBLE] AND I'VE WRITTEN SOME OF THEIR FEEDBACK FROM THEIR DISCUSSION ABOUT THIS CONCEPT BUT IN SUMMARY, THEY FELT THE STRONGEST ARGUMENT WAS THE NEED TO ADDRESS A VERY UNDERRESEARCH DIVERSE ORDER ON PATHOGENS THEY FELT IT WAS TIMELY AND THE WORK SHOULD BE DONE NOW IF NEEDED YOU COULD THEN PIVOT TO ADDRESS FUTURE OUTBREAKS OR EPIDEMICS. THEY LIKE THE IDEA THAT INFORMATION GAINED FROM THE GRANTS WOULD HELP SUPPORT CREID EFFORTS AND OVERALL THEY FELT IT WAS A MODEST INVESTMENT WITH A POTENTIAL BIG RETURN AND OVERALL WAS SUPPORTIVE. SO IN SUMMARY 1 LESSON WE LEARNED FROM THE COVID-19 PANDEMIC IS THAT WE NEED BASIC RESEARCH INTO PRIORITY PATHOGENS THAT COULD EMERGE AND THEN IF NEEDED USE THIS INFORMATION TO DEVELOP OUTBREAK RESPONSE MEASURES AND INTERVENTIONS. THIS CONCEPT SEEKS TO DO JUST THAT BY ADDRESSING THE BASIC SCIENCE RESEARCH GAPS IN THE SUBMERGING AND REEMERGING GROUP OF VIRAL PATHOGENS. BEFORE I END, I WOULD LIKE TO ACKNOWLEDGE ALL MY COLLEAGUES IN THE I HAVEROLOGY BRANCH OUR CHIEF, MARK [INDISCERNIBLE], OUR SECTION CHIEF, AND [INDISCERNIBLE] FOR ALL THEIR HELPFUL ADVICE AND DEVELOPING NOT JUST THIS PRESENTATION BUT IN DISCUSSION OF DEVELOPMENT OF THIS CONCEPT. I WANT TO THANK YOU FOR YOUR TIME AND CONSIDERATION OF THIS CONCEPT, AND I WILL BE ABLE TO TAKE ANY QUESTIONS YOU MIGHT HAVE. >> THANK YOU RUDI, ANY QUESTIONS FOR RUDI? OR ADDITIONAL COMMENTS FOR ANNA OR HARRY? >> FOR ME, I THINK THIS IS REALLY SMAG IS A NO BRAINER--SOMETHING THAT IS A NO BRAINER. A LOT OF BASIC I HAVEROLOGY OF VIRUSES AND THESE VIRUSES THAT REALLY LETHAL AND THEY'RE REALLY IMPORTANT WHEN THEY HAVE AN OUTBREAK SO I THINK--I HOPE THAT THERE ARE 10-14 GROUPS THAT APPLIED TO THESE AND THEN IT WILL BE A COMPETITIVE APPLICATION AND THE EXPERTISE TO REVIEW THESE GRANTS IS ALSO ACHIEVED BUT I THINK THIS IS REALLY IMPORTANT. IT WILL FILL A REALLY IMPORTANT GAP AND I THINK RIGHT NOW ALSO, AS I THINK WAS MENTIONED BY RUDI, THAT NOW ALL THESE NEW COHORTS AND RESOURCES THAT HAVE BEEN SET OUT FOR SARS-COV-2, THAT COULD MAYBE IDENTIFY NEW ISOLATES AND REALLY HELP SO IT SHOULD BE REALLY IMPORTANT TO PLUG INTO THOSE RESOURCES. YEAH. >> I BASICALLY TOTALLY AGREE WITH ANNA. THEY'RE AMAZINGLY DIVERSE, I HADN'T REALIZED HOW MANY OF THEM THERE ARE AND THEY'RE ACTUALLY PRETTY WEIRD DENOAMS AND ALMOST NONE OF THEM HAVE A REVERSE GENETIC SYSTEM YET DEVELOPED INTERESTINGLY. SO, THEY REALLY RIPE FOR SOME BASIC FINDINGS AND WE'VE SEEN WITH THE CORONAVIRUSS, WE WOULD HAVE REALLY BEEN UP THE CREEK HAD THERE NOT BEEN SOME WORK DONE BEFORE HAND. SO I THINK THEY'RE WELL WORTH A MORE BASIC INVESTMENT. >> WELL THIS IS KEN. SO I HAVE A SIMILAR QUESTION, I GUESS IT'S A QUESTION, GIVEN THE DIVERSITY AND YOU KNOW THE LIMITED AMOUNT OF WORK THRA'S DONE IN KNOWLEDGE, ARE THERE REFERENCE STRAINS OR REFERENCE CENTERS AND WHAT'S THE RESOURCES THAT ARE AVAILABLE AND WITH THIS--WOULD THIS BE--THESE RESOURCES BE AVAILABLE TO THE APPLICANTS? >> YES, IT'S A VERY GOOD QUESTION. SO WE HAVE OUR BI--RESOURCES REPOSITORY WHICH WILL ESSENTIALLY BE AVAILABLE TO ALL OF THE PIs IN THE FIELD. WE ALSO HAVE A GRANT WHICH IS THE--CALLED RECEIVA AND HAS A LOT OF POSITIVE STRAINs AS WELL AND COULD BE ACCESSED BY THE RESEARCH COMMUNITY. >> ANY RECOLLECT QUESTIONS FOR RUDY? >> OKAY, THANK YOU. IF NOT LET'S GO AHEAD AND ENTER YOUR VOTES IN THE ELECTRONIC COUNCIL BOOK. AND I AM GOING TO INTRODUCE THE NEXT SPEAKER WHICH IS MAR SIGNIFYELLA DEGRACE, SHE WILL PRESENT THE INITIATIVE TO DO SYSTEMS APPROACH TO BED MECHANISMS OF HETEROGENEOUS ROW GEANIOUS RESPONSE TO INFLUENZA. MARCIELA? >> HI, EVERYONE. CAN EVERYBODY HEAR ME? >> GREAT. >> SO I WILL STICK WITH AS RUDY STARTED OFF WITH SEGMENTED NEGATIVE STRAND RNA VIRUSES AND WE GALLON TO INFLUENZA AND TO THE CONCEPT NOW IT WAS A SYSTEMS APPROACH TO UNDERSTAND MECHANISMS OF HETEROGENEOUS ROW GENIUS RESPONSE TO INFLUENZA, AND OUR GOAL HERE IS TO TRY TO UNDERSTAND THE VARYING RESPONSES YOU SLEEP APNEA AND OBESITYY TO BOTH INFLUENZA INFECTION AND VACCINATION AND TO DO THAT THROUGH THE DEVELOPMENT AND APPLICATION OF COMP YOU HADITATIONAL TOOLS AND WE HOPE THAT THROUGH THAT WE WILL IMPROVE INFLUENZA VACCINE DESIGN. THIS A NEW CONCEPT, WE ARE HOPING TO AWARD 4-6 AWARDS AND THE FIRST COST WILL BE $4 MILLION. SO WE'RE AT NIAID FUND A LARGE NUMBER OF PROGRAMS LOOKING AT RESPONSES TO INFLUENZA VACCINATION OR INFECTION, WE HAVE THE SEERS NETWORK WHICH IS A BASIC INFLUENZA AND RESEARCH NETWORK, WE HAVE OUR CIVICS PROGRAM FOCUSED ON THE UNIVERSAL INFLUENZA VACCINE, A PROGRAM ON INFINITE IMMUNITY, VACCINE ASK STREEMENT AND STUDY VACCINES AND THEN THE HEP-Cs, LIKE PROJECT CONSORTIUM SO THERE'S A NUMBER OF PROGRAMS GENERATING DATA, CLINAL DATA ON HOW PEOPLE RESPOND TO INFLUENZ OR INFECTION OR VACCINATION AND SO, 1 THING THAT WE'VE NOTICED IS A SCIENTIFIC NEED AND OPPORTUNITY IS THAT OUR ABILITY TO GENERATE THESE LARGER DATA SETS STUDYING THESE QUESTIONS THAT THEY'VE ADVANCED FASTER THAN THE TOOLS WE MAY NEED TO EXTRACT MEAN FREE RADICALS GENERATED ALL THIS DATA SO A QUESTION IS, YOU KNOW WHAT RESEARCH QUESTIONS WOULD BENEFIT MOST FROM COMPUTATIONAL TOOL DEVELOPMENT, FROM TAKING, YOU KNOW THIS DIVERSE AMOUNT OF DATA POINTS WE HAVE AND DEVELOPING TOOLS TO ACTUALLY REALLY FILTER DOWN AND GET HYPOTHESIS AND POSSIBLE COUNTER MEASURE STRATEGIES. YOU KNOW CAN WE USE COMPUTATIONAL TOOLS IN THIS WAY TO HELP US--VACCINE DESIGN. AND SO 1 OF THE QUESTIONS THAT WE THINK LENDS ITSELF REALLY WELL TO THE USE OF COMPUTATIONAL TOOLS TO HELP FILTER DOWN DATA SETS IS RESPONSES TO INFLUENZA VACCINATION AND INFECTION, SO SOMETHING WE KNOW IS THAT PEOPLE RESPOND VERY DIFFERENTLY TO THE SAME INFLUENZA VACCINE. AND THAT PEOPLE WILL RESPOND DIFFERENTLY TO THE SAME--TO INFECTION WITH THE SAME INFLUENZA STRAIN AND SO, THE QUESTION OF WHY SOME PEOPLE ARE BETTER ABLE TO RESPOND BETTER TO THE INFLUENZA VACCINE THAN OTHERS AND THE QUESTION OF WHY SOME PEOPLE WHO WERE PREVIOUSLY SEEN TO BE SOMEWHAT HEALTHY WILL HAVE A DISEASE OF DIFFERENT SEVERITY FOR INFLUENZA, THOSE ARE STILL OPEN QUESTIONS IN THE FIELD. WE DO KNOW THERE ARE SOME CHART IEOF THETICS THAT MATTER--CHARACTERISTICS THAT MATTER AND WE THOUGHT GENETICS WILL THOUGHT TO PLAY A ROLE BUT NOT A HUGE ROLE. WE KNOW THERE ARE CHARACTERISTICS LIKE OBESITY IN THE MICROBIOME, BUT WE DON'T LEGALLY UNDERSTAND AWE WILL CONTRIBUTES FACTORS TO VACCINATION AND INFECTION. SO AS I MENTIONED, YOU KNOW SOME OF THE BIG THINGS THAT HAVE COME OUT IN RESEARCH ARE GENETIC POLYMORPHISMS, IMMUNE HISTORY AND SO RESPONSES TO INFECTION OR VACCINATION IN THE PAST, BIOLOGICAL SEX, IMMUNE O SENESCENSEL AND UNDERLYING MEDICAL CONDITIONS. AND SO, WE DO KNOW THAT THERE'S SOME BROAD CATEGORIES THAT CONTRIBUTE BUT WE DON'T SORT OF UNDERSTAND THE FULL MECHANISMS OF WHY PEOPLE HAVE VARYING RESPONSES AND AT THE SAME TIME WE ARE STARTING TO SEE THAT COMPUTATIONAL TOOLS DO HAVE THE POWER TO GIVE US SOME ANSWERS HERE AND SO, IESM JUST HIGHLIGHTING 2 PAPERS HERE, WHERE LOOKING AT, YOU KNOW ANALYSIS OF IMMUNE VARIATION, YOU YOU COULD SEE IT LOOKING AT A BASE LINE BLOOD DRAW IN LOOKING AT BASE LINE CHARACTERISTICS YOU COULD ACTUALLY PREDICT WHO WOULD BE ABLE TO RESPOND TO VACCINE AND WHAT THE POST VACCINATION RESPONSES WILL BE AND SO, ON THE RIGHT I'M SHOWING A PAPER WHERE A TOOL CALLED SIMON WAS DEVELOPED USING MACHINE LEARNING TO REALLY UNDERSTAND IMMUNE SIGNATURES FOR FAC SEEN RESPONSES AND UNDERSTANDING THAT SOMETIMES EVEN THOUGH THE BASE LINE POPULATIONS OF CELLS, PERCENTAGES OF TYPES OF CELLS, DIFFERENT THINGS LIKE THAT MAY BE ABLE TO PREDICT THE TYPES OF OUTCOMES PEOPLE WILL HAVE AND SO, YOU KNOW WE DO THINK THAT THESE COMPUTATIONAL TOOLS ARE STARTING TO SHOW PROMISE IN THIS AREA. AND SO WHAT WE'RE THINKING FOR OUR CONCEPT IS WE WOULD REALLY LIKE TO START FUNDING RESEARCH WHERE WE CAN PARTNER COMPUTATIONAL EXPERT WHO IS CAN BUILD THESE TYPES OF TOOLS WITH INFLUENZA SCIENTISTS WHO HAVE THESE DATA SETS OR IN THE PROCESS OF DEVELOPING THESE DATA SETS AND HAVE SAMPLES AND SO WE WOULD LIKE TO CREATE THAT PARTNERSHIP AND APPLY COMPUTATIONAL TOOLS TO IDENTIFY MECHANISMS BEHIND THE HETEROGENEOUS ROW GENIUS RESPONSE TO INFECTION. SO, YOU KNOW THE BEARING OUTCOMES OF DISEASE SEVERITY OR VACCINATION, SO OUR GOAL WOULD BE HERE THAT THE TOOLS WOULD IDENTIFY MARKERS, OR PREDICTERS OF RESPONSE OR NONRESPONSE TO VACCINE, OR EVER SEVERE OUTCOME TO INFECTION AND WE WOULD LIKE THE PROGRAM TO BE BASED ON HUMAN DATA AND WE KNOW THAT ANIMAL MODELS HAVE THEIR USES BUT WE KNOW THAT ANIMAL MODELS LIE AND WE HAVE A ACCESS TO A THE LO OF HUMAN DATA THROUGH THE PROGRAMS THAT I MENTIONED EARLIER. IF POSSIBLE WE WOULD LIKE TO SEE BUILT INTO THE PROGRAM A COMOPPOSITE BEHAVIORIAL PHENOTYPE THAT HE WENT ENABLES OUTREACH FROM PEOPLE WHO BUILD THESE COMPUTATIONAL TOOLS TO INFLUENZ THE SCIENTISTS. AGAIN, TRYING TO CREATE THAT PARTNERSHIP, TO FURTHER THIS RESEARCH AREA. SO I THINK THIS IS A SLIDE THAT YOU ALL HAVE SEEN IN YOUR ROLE AT COUNCIL, MANY TIMES BEFORE, BUT UNIVERSAL INFLUENZA VACCINE STRATEGIC PLAN WAS RELEASED AND IT HAS 3 MAIN RESEARCH AREAS, AND 4 CROSS CUTTING AREAS THAT WERE OUTLINES AND SO, THE RESEARCH AREAS FOCUSED ON BASIC RESEARCH OF IMPROVING OUR UNDERSTANDING OF TRANSMISSION, NATURAL HISTORY AND PATHOGENESIS OF INFLUENZA, RESEARCH AREA 2 FOCUSES ON INFLUENZA IMMUNITY AND CORRELATESSIVE PROTECTION AND THEN RESEARCH AREA 3 FOCUSES ON VACCINE DESIGN. BUT THE CROSS CUTTING AREAS ARE AREAS THAT ARE NECESSARY TO ENABLE THE RESEARCH ACROSS ALL 3 OF THOSE RESEARCH AREAS AND THE CROSS CUTTING AREAS INCLUDE THINGS LIKE IMPROVING ANIMAL MODELS AND REAGENTS, ESTABLISHING COHORTS, CHALLENGE STUDIES AND THEN DEVELOPING AND APPLYING SYSTEMS BIOLOGY APPROACHES. AND SO, SINCE THIS PLAN WAS CREATED A FEW YEARS AGO, WE'VE BYE-BYE TRYING TO CREATE TARGETED INITIATIVES AND FUND INVESTIGATOR INITIATED AWARDS TO REALLY BUILD OUT THESE RESEARCH AREAS, BUT 1 OF THE RESEARCH AREA THAT REALLY REMAINS UNDER FUNDED AND UPDATER TARGETED BY ANY OF OUR INITIATIVES IS CROSS CUTTING AREA FOR THE DEVELOPMENT AND APPLICATION OF SYSTEMS BIOLOGY APPROACHES. SO AS CAN YOU SEE HERE, MAIN OF OUR OTHER CROSS CUTTING TOOLS ARE COVERED IN SOME OF OUR OTHER RESEARCH PROGRAMS, WE HAVE, YOU KNOW ANIMAL MODEL PROGRAM ANNOUNCEMENTS--AND OUR SIEVE CLINICAL COMMUNITY WHICH IS OUR VACCINE PROGRAM, BUT WE DON'T REALLY HAVE ANYTHING THAT FOCUSES HERE AND SO THAT'S PART OF OUR GOAL WITH THIS INITIATIVE IS TO FILL THIS GAP OF TRYING TO DEVELOP AND,A PLIE SYSTEMS BIOLOGY APPROACHES AND BUILD EXPERTISE IN THAT AREA, FOR THE INFLUENZA FIELD SO THAT WE CAN BUILD THE TYPES OF TOOLS THAT WE WANT TO ENABLE BETTER VACCINE DESIGN. SO WE SEE A LOT OF GENERATED FIT--BENEFIT FROM THIS, WE MAY IDENTIFY VARIANCE RESPONSES TO INFLUENZA AND VACCINATION, THAT'S IMPORTANT FOCUS ON THE ONLY TO HAVE THESE BIOMARKERS BUT TO FIGURE OUT HOW WE CAN TARGET THOSE AREAS TO IMPROVE VACCINE DESIGN. WE THINK IF WE HAVE THOSE BIOMARKERS, WE WILL BE ABLE TO ENABLE BETTER TREATMENTS OR DERISK VACCINE DEVELOPMENT. WE WOULD LIKE TO BE ABLE TO APPLY NEW TOOLS TO EXPLORE INFLUENZA DATA SETS SO AGAIN TRYING TO GET THE MOST INFORMATION WE POSSIBLY CAN OUT OF OUR LARGE PROGRAMS AND OUT OF OUR LARGE CLINICAL STUDIES TO REALLY MINE THE INFORMATION THAT THEY HAVE IN THERE AND LEARN MORE FROM THEM AND POSSIBLY THROUGH COMPUTATIONAL TOOLS COMBINE ACROSS DIFFERENT PROGRAMS AND ACROSS DIFFERENT DATA SETS TO MAKE DISCOVERIES THAT WE MAY NOT HAVE BEEN ABLE TO MAKE BEFORE. IT ADDRESSES AN AREA OF OUR UNIVERSAL INFLUENZA VACCINE STRATEGIC PLAN THAT CURRENTLY IS UNTARGETTED, AND WE ALSO HOPE TO SEE IT GROW OUR COMPUTATIONAL EXPERTISE IN THE INFLUENZA FIELD. WE HAVE IN THE PAST 5 YEARS GOTTEN 53 UNSOLICITED APPLICATIONS IN THIS AREA, AND WE'VE BEEN ABLE TO MAKE 8 AWARDS SO IT'S IT'S--WE DON'T GET A LOT OF APPLICATIONS, 53 OVER NIEF YEARS ISN'T THAT MUCH AND WE ALSO DON'T SEE THEM BEING VERY SUCCESSFUL SO YOU KNOW A SMALLER TARGETED INITIATIVE WILL HOPEFULLY HELP US BUILD THE EXPERTISE IN THIS AREA. SO I GOT TO TALK TO DR. FERNANDEZ AND DR. STEWART ABOUT THIS INITIATIVE AND GOT GREAT FEEDBACK. I THINK THAT, YOU KNOW WE ALL DISCUSSED IT'S AN IMPORTANT AREA AND IMPORTANT TO ELEVATE THE ROLE OF COMPUTATIONAL SCIENTISTS AND COMPUTATIONAL EXPERTISE BEYOND JUST TOOL DEVELOPMENT, SOMETIMES THESE PEOPLE HAVE ROLES ON PROG ELECTRIC LIGHTINGS THAT END UP BEING MORE OF A CORER RESOURCE AND SO THIS AN OPPORTUNITY TO ELEVATE TO THE PI LEVEL. ONE AREA THAT I THINK WE'VE ALL TALKED ABOUT IS THAT WE MAY NEED TO DO SOME OUTREACH TO ENCOURAGE THAT WE'RE RECRUITING THE RIGHT PEOPLE SO REALLY MAKING SURE THAT WE REACH THE RIGHT COMMUNITIES WITH OUTREACH HERE THAT WE GET THE RIGHT PEOPLE IN THE DOOR TO DO THIS SORT OF THING. IT'S AN IMPORTANT CHANCE TO SORT OF MARRY COMPUTATIONAL EXPERTISE AND INFECT YOWZ DISEASE EXPERTISE AND WHILE WE'RE FOCUSING ON INFLUENZA NOW, THERE'S POTENTIAL HERE THAT WHAT COMES OUT OF THIS COULD BE BENEFICIAL TO OTHER AREAS AND OTHER PAGLIARULO O GENS IN THE FUTURE. YOU KNOW SOME OF THE THINGS WE TALKED ABOUT BEYOND THAT, IS CONSIDERING THE EXTRINSIC AND INTRINSIC REGIONS BEHIND HETEROGENEOUS ROW GENERATED AIC AND INCREASE THIS TO THINK ABOUT BOTH THE INNATE FACTORS AS WELL AS ENVIRONMENTAL AND OTHER FACTORS THAT COULD BE CONTRIBUTING. THEN 1 THING WE DISCUSS WAS CO FUNDING, AGAIN WITH THE IDEA MAINLY TO MAKE SURE WE'RE USING ALL AVENUES POSSIBLE TO ADVERTISE AND BRING IN AND MAKE SURE WE GET THE RIGHT EXPERTISE IN AND ENDORSEMENT THAT THE PROGRAM COULD BE SUCCESSFUL. AND SO REQUEST THAT I AM HAPPY TO TAKE ANY QUESTIONS AND YOU KNOW TALK ABOUT THIS PROGRAM WITH YOU ALL. >> THANK YOU MARCIE LA. >> QUESTIONS OR ADDITIONAL QUESTIONS? >> I WOULD LIKE JUST TO ADD THAT BASED ON OUR CONVERSATION, YOU KNOW AND BEING PART OF BIG INITIATIVES AND GOOD, A LOT OF THESE INVESTIGATORS HAVE GENERATED A LOT OF PRELIMINARY DATA SO I THINK THIS WOULD BE VERY USEFUL FOR PEOPLE TRYING TO LAUNCH THEIR OWN CAREERS OR TRY TO GET INDEPENDENT FUNDING TO REALLY USE THAT OPPORTUNITY TO BE PART OF THESE BIG GROUP TO REALLY DEVELOP A CAREER BETTER AND THEY WILL HAVE EXPERTISE NOT ONLY IN INFLUENZA BUT OTHER PATHOGENS OR EVEN LIKE CANCER OR OTHER FIELDS SO I THINK IT WILL BE REALLY IMPORTANT TO GIVE THIS IMPORTANCE TO THIS APPROACH, YEAH. ABSOLUTELY. >> THIS IS KEN, SO I REALLY AGREE WITH THOSE COMMENTS, I THINK THIS IS AN EXCITING INITIATIVE NCHT IN A CERTAIN SENSE IT'S AN EXPERIMENT BECAUSE WE'RE NOW TRYING TO MARRY 2 SORT OF OVERLAPPING FIELDS AND I THINK THAT THE COMPUTATIONAL BIOLOGISTS HAVE REALLY BEEN MORE INVOLVED IN TOOL DEVELOPMENT THAN ACTUALLY AND ALSO LEVERAGES A LOT OF THE INVESTMENTS THAT HAVE BEEN MID BY NIH AND OTHERS IN GENERATING A LOT OF THE DATA AND I THINK THERE'S A LOT OF EXISTING INFRASTRUCTURE, EXISTING DATA AND INFRASTRUCTURE TO ACCESS THAT DATA, ET CETERA THAT WILL BE VERY USEFUL TO THE PROGRAM AND THE INITIATIVE IS PUTTING IT IN THE CONTEXT OF NOT JUST HAVING THE COMPUTATIONAL BIOLOGIST BEING ESSENTIALLY CONSULTANTS WORKING CONSULTANTS THAT ARE WORKING ON THE DAILY BASIS AT BUT TO BE VERY MUCH INVOLVED IN THE--HOW THOSE DATA WILL BE MOST USEFUL. >> ONE THING WE COMMENTED ALSO WITH MAR SIGNIFYELLA WAS NOT TO CONFUSE WITH THIS [INDISCERNIBLE] GRANTS. YOU KNOW TO HAVE A BIT MORE EMPHASIS IN USING TOOLS TO REALLY ANALYZE THE DATA THAT IS EXISTING BECAUSE THERE ARE ALSO OTHER SYMPTOMS OF MODELING THAT ARE A BIT MORE KIND OF LIKE FULFILLING ANOTHER FUNCTION. SO THAT'S ALSO KIND OF FORTUNATE HAVE THIS SPECIFIC FOCUS HERE. NANY OTHER QUESTIONS? OKAY, SOPHISTICATEDY THANK YOU MARCIELA, SO THIS ENDS THE PRESENTATION FOR TODAY. BEFORE WE ADJOURN, I WOULD LIKE TO MAKE SURE THAT--PLEASE CHECK THAT YOU ENTER YOUR VOTES IN THE ELECTRONIC COUNCIL FOR EVERY SING ILLEGALS INITIATIVE INCLUDING THE RBLs AND THE CONCEPTS FOR ADRs SO PLEASE TAKE A MEMORY CLONE TONIGHT MAKE SURE EVERYTHING HAS BEEN COMPLETED. AND I WOULD LIKE TO THANK AGAIN, ALL THE PARTICIPANTS TO THIS MEETING, WE'RE GOING TO END A LITTLE EARLIER SO WE WILL GIVE YOU AN HOUR BACK AND I WOULD LIKE TO THANK ESPECIALLY OUR COUNCIL MEMBERS AT THE END--THERE'S EMILY. >> YES, I'M BACK FOR MY EMERGENCY CALL, SO I'M GLAD, YOU KNOW SOMETIMES YOU GET RECALLED IF WE DON'T HAVE PEOPLE TO FILL YOUR SEATS IN THE NEXT ROUND SO THAT MIGHT HAPPEN BUT THANK YOU AGAIN FOR ALL OF YOUR SERVICE. WE ACTUALLY RELY A LOT UPON YOUR OPINIONS AND YOUR INPUT IN DEVELOPING OUR PROGRAMS. >> PLEASURE, EMILY. >> SAME HERE. >> THANK YOU ALL. >> GOOD TO SEE YOU ALL. >> EMILY WOOER ABOUT TO WRAP UP. I THINK EVERYBODY CHECKED THEIR VOTES. AND WE'RE ABOUT TO SAY GOODBYE. >> OKAY. >> FAREWELL. >> UNTIL WE MEET AGAIN!