>> I'M KEN FREEDBERG, CHAIR OF
THE AIDS RESEARCH ADVISORY
COMMITTEE, I WANT TO WELCOME
EVERYONE TO THE JUNE 6 VIRTUAL
MEETING OF ARAC. WE HAVE A FULL
INTERESTING AGENDA.
WE WILL START OFF WITH APPROVAL
OF THE MINUTES OF OUR JANUARY
31ST MEETING AND CAN I HAVE A
MOTION TO APPROVE THOSE MINUTES?
>> SO MOVED.
>> SECOND ANYONE?
>> SECOND.
>> GREAT SO THIS IS A MOTION TO
APPROVE MINUTES OF JANUARY 31ST,
ANY DEBATE ON THAT?
NO DEBATE.
WHY DON'T WE HAVE A VOTE THEN.
EVERYONE IN FAVOR OF APPROVING
THE MINUTES?
>> AYE.
>> ANYONE OPPOSED?
HEARING NONE THE MOTION IS
PASSED TO APPROVE THE MINUTES.
IT WAS A GREAT MEETING.
ANYONE WHO WANTS TO REREAD THEM,
FANTASTIC MEETING.
LET ME TURN THIS OVER NOW TO DR.
CARL DIEFFENBACH, DIRECTER OF
THE DIVISION OF AIDS, LOOK
FORWARD TO HEARING FROM YOU.
>> THANK YOU, KEN A PLEASURE.
CAN SOMEBODY PLEASE CALL UP MY
SLIDES?
NEXT SLIDE PLEASE.
GOOD AFTERNOON, EVERYONE.
WELCOME TO JUNE MEETING OF THE
AIDS RESEARCH ADVISERY
COMMITTEE.
WELCOMING TO JONAH SASCHA NEW
OFFICE OF COUNCIL LIAISON TO
ARAC.
AND JONAH RECEIVED HIS Ph.D.
FROM THE UNIVERSITY OF WISCONSIN
MADISON AND THE LAB OF ANOTHER
PROMINENT PRIME TOLL GIST, DR.
DAVID WATKINS AFTER HE JOINED
THE FACULTY AT UDUB MEDICINE
AFFECTING RETRO VIRUS SPECIFIC
CD4 CD8 CELLS.
IN 2011 HE JOINED THE OREGON
HEALTH AND SCIENCE UNIVERSITY
WITH APPOINTMENTS IN VACCINE AND
GENE THERAPY INSTITUTE AND THE
OREGON NATIONAL PRIMATE RESEARCH
CENTER.
HIS RESEARCH INTERESTS INCLUDE
T-CELL BIOLOGY, RETRO VIRUSES
VACCINE DEVELOPMENT.
PLEASE JOIN ME IN WELCOMING
JONAH.
THANK YOU FOR JOINING AS OARAC
LIAISON.
I THINK IT IS IMPORTANT I WANT
TO SPEND A LITTLE TIME ON THE
BUDGET, IT IS KIND OF COMPLI
COMPLICATED, SO I LIKE TO WALK
YOU THROUGH IT.
YOU SEE THE NIAID RECEIVED ABOUT
A 4.2 INCREASE IN FISCAL YEAR 22
AS ENACTED.
WHICH WAS A VERY NICE AMOUNT.
THEN AS WE LOOK AT THE REQUEST
FOR THE PRESIDENT'S BUDGET FOR
'23, WE SEE A LITTLE BIT OF
ANOMALY THAT IT IS PROPOSED TO
GO DOWN A LITTLE BIT.
AS DR. FAUCI EXPLAINED EARLIER
TODAY, THIS IS LARGELY DUE TO
THE FACT THAT THE BUDGET WAS
BUILT PRIOR TO THE APPROVAL OF
THE FINAL FY 22 BUDGET.
NEXT SLIDE PLEASE.
SO FOR FISCAL YEAR 22 WE HAVE
DECIDED TO MAINTAIN THE
ESTABLISHED PI PAY LINE AT THE
12TH PERCENTILE.
THE NEW PI PAY LINE AT THE 16TH
PERCENTILE.
NO COMPETING OR NON-COMPETING
ADJUSTMENTS, RESEARCH PRIORITIES
WILL CONTINUE TO RECEIVE
ATTENTION AND THE ESTIMATED
SUCCESS RATE WE ARE STILL HOPING
TO RECEIVE TO MAKE IT AT ABOUT
18 TO 22ND PERCENTILE.
I THINK IT IS IMPORTANT TO THINK
ABOUT WHERE WE GOT A 4.2%
INCREASE BUT WHERE DID THAT
MONEY GO?
IT IS IMPORTANT TO GO BACK AND
REVISIT THIS QUESTION OF EAR
MARKS.
YOU CAN SEE THE AMOUNT THAT WE
-- THERE WAS A FAIR AMOUNT OF
INCREASE IN EAR MARKS THIS CYCLE
FROM 10 MILLION FOR CFARS TO
ADDITIONAL INCREASES IN A NUMBER
OF OTHER EARMARKS AS YOU CAN SEE
AMR WENT UP BY 15 MILLION, ONE
OF THE BIGGER ISSUES WAS THIS
$52 MILLION IMPACT OF THE RBLs
OVERALL ON THE BUDGET.
SO WHILE THE BUDGET WENT UP SO
DID THE EARMARKS AND THAT MAKES
FOR A RELATIVELY TIGHT PAY LINE.
I WILL PAUSE THERE AND SEE IF
PEOPLE HAVE ANY SPECIFIC
QUESTIONS ON THE BUDGET.
HEARING NONE WE CAN BRING THESE
UP AT END.
I WANT TO SPEND SOME TIME
TALKING ABOUT SCIENTIFIC
PROGRAMMATIC UPDATES.
THIS CYCLE I'M GOING TO SPEND A
LITTLE BIT MORE TIME ON
PROGRAMMATIC UPDATES RELATED TO
DIVERSITY EQUITY INCLUSION AND
ACCESSIBILITY.
THIS REPRESENT IT IS WHOLE OF
NIH AND OVERARCHING RESEARCH
PRIORITIES.
THIS IS THE SLIDE THE OFFICE OF
AIDS RESEARCH USES TO REALLY
FOCUS IN ON THE TOP PRIORITIES
OF REDUCING INCIDENTS RESEARCH
TOWARDS A CURE, NEXT GENERATION
THERAPIES CO-MORBIDITIES AND THE
CROSS CUTTING AREAS.
AS WE LOOK AT NIAID IN OUR
STRATEGIC GOALS WE SEE OUR
STRATEGIC GOALS ROLL ALIGNED
WITH NATIONAL HIV AIDS STRATEGY
AND ARE FOCUSED ON ENDING THE
HIV EPIDEMIC.
WHEN ADVANTAGEOUS WE AS AN
ORGANIZATION SEEK TO ACHIEVE OUR
GOALS TO ESTABLISHMENT OF
STRATEGIC PARTNERSHIPS, WITHIN
THE NIH WITHIN HHS WITHIN THE US
GOVERNMENT OVERALL WITH OTHER
GOVERNMENTS AND OUTSIDE GROUPS
SUCH AS PHARMA, THE GATES
FOUNDATION AND INTERNATIONAL
AIDS VACCINE INITIATIVE.
PRINCIPLE THAT WE COMPLETELY
BELIEVE IN AND PRACTICE IS
CONSULTATION WITH COMMUNITY AS
AN ESSENTIAL ELEMENT OF OUR
PROCESSES.
AND WE EVALUATE OUR ACTIVITIES
THROUGH THE LENS OF DIVERSITY
EQUITY AND INCLUSION AND ACCESS.
SO I WANT TO SPEND TIME TALKING
WITH YOU AS THE COUNCIL ON WHAT
WE ARE SPECIFICALLY DOING BOTH
INTERNALLY AND EXTERNALLY IN
THIS AREA OF CIVILITY AND
DIVERSITY AND WE HAVE BEEN
INTERESTED PUSHING ON MANY OF
THESE QUESTIONS FOR A VERY LONG
TIME.
MANY OF THE THINGS WE HAVE DONE,
MANY ACCOMPLISHMENTS HAVE BEEN
DONE QUIETLY.
YOU CAN IMAGINE WHY THAT WOULD
BE IF YOU THINK BACK TO 2016,
AND WE ARE PLEASED WITH THE
PROGRESS WE HAVE MADE MAINLY
THROUGH DIVERSITY ACTIVITIES
THROUGH NETWORKS AND OTHER LARGE
MULTI-DISCIPLINARY FUNDING
ACTIVITIES SUCH AS CFAR AND THE
NETWORKS.
SO NIAID IS ESTABLISHED A
WORKPLACE CIVILITY TASK FORCE TO
PROVIDE EPIPUT ON AND CHAMPION
WORKPLACEVILLETY AND
ANTI-HARASSMENT EFFORTS ACROSS
THE INSTITUTE.
WE ESTABLISHED A DEIA COUNCIL TO
HELP NIAID PLAN TO ADDRESS DEIA
INCLUDING OUR INTERNAL WORK
FORCE, THE EXTRAMURAL WORK FORCE
AND IN RESEARCH TO PROMOTE
ADDRESS HEALTH DISPARITIES.
ONE OF THE THINGS YOU WILL HEAR
ABOUT TODAY IS A FUNDING
ANNOUNCEMENT BEING BROUGHT
FORWARD AS A CROSS NIAID
ACTIVITY THAT I THINK IS
IMPORTANT.
THAT IS ONE OF THE REASONS I'M
SPENDING TIME ON A LITTLE
BACKGROUND ON THIS TOPIC.
NEXT SLIDE PLEASE.
SO A WORD OR TWO ABOUT WORK
FORCE CIVILITY TASK FORCE.
WE DEFINE CIVILITY AS AN
EXPECTATION STATEMENT TO CREATE
A CIVIL WORKPLACE NIAID EXPECTS
ALL STAFF REGARDLESS OF
BACKGROUND OR POSITION TO ACT
WITH PROFESSIONALISM AND
RESPECT, LISTEN WITH AN OPEN
MIND, COMMUNICATE CONSTRUCTIVELY
AND WORK COLLABORATIVELY IN
SUPPORT OF THE NIAID MISSION.
THIS WAS THE CIVILITY WORKPLACE,
CIVILITY PLEDGE WAS DEVELOPED
FOR EMPLOYEES BY EMPLOYEES.
NEXT SLIDE PLEASE.
THERE'S A GRAPHIC WE PREPARED
THAT IS PRINCIPLE PEOPLE CAN PUT
UP IN THEIR OFFICE.
YOU CAN SEE IT HERE.
BASICALLY IT HIGHLIGHTS EACH OF
THE TOPICS THAT I MENTIONED
INCLUDING THINGS LIKE LISTEN
ACTIVELY.
NEXT SLIDE PLEASE.
FOR DIVERSITY EQUITY INCLUSION
AND ACCESS CIVILITY COUNCIL,
HERE IS A STATEMENT ABOUT IT IN
ACHIEVING ITS MISSION TO BETTER
UNDERSTAND TREAT AND PREVENT
INFECTIOUS IMMUNOLOGIC ALLERGIC
DISEASES NIAID IS COMMITTED TO
DIVERSITY EQUITY INCLUSION
ACCESSIBILITY THROUGH FOSTERING
A DIVERSE INCLUSIVE WORK FORCE
AND WORKPLACE FOR ALL STAFF
FUNDING EXTRAMURAL RESEARCH
PORTFOLIO THAT IS REPRESENTATIVE
OF THE DIVERSE POPULATION ITS
SERVES AND PRIORITIZING HEALTH
EQUITY IN ALL RESEARCH NIAID
CONDUCTS AND SUPPORTS.
AS WAY OF HELPING THE DEIA
COUNCIL BECOME ACTIONABLE AND
MOVE FORWARD TO WORK GROUPS WHO
ESTABLISH ONE LOOKING AT THE
INTERNAL WORK FORCE AND THE
SECOND WAS EXTRAMURAL WORK GROUP
LOOKING AT EXTRAMURAL COMMUNITY.
WE ARE NOT THE ONLY ONES AT NIH
WHO HAVE BEEN WORKING ON THIS.
WE ARE BIG ON WE SEE BEST
PRACTICES TAKING THEM AND
ADAPTING THEM FOR OWN NEEDS,
THERE WAS A PLAN DEVELOPED BY
THE BRAIN DIVERSITY INITIATIVE
CALLED THE PLAN FOR ENHANCING
DIVERSE PERSPECTIVES.
THIS WAS TO PUT IN A NEW
COMPONENT INTO FUNDING
OPPORTUNITY ANNOUNCEMENTS THAT
WOULD BE PART OF THE BRAIN
INITIATIVE FOR PIs AND
RESEARCH INSTITUTIONS TO TALK
ABOUT AND BRING FORWARD DIVERSE
PERSPECTIVES AND BRING ALONG THE
CULTURE CHANGE NECESSARY TO
ADDRESS THE INEQUITIES AND
SYSTEMATIC BIASES IN BIOMEDICAL
RESEARCH WHILE ADVANCING
SCIENTIFIC INNOVATION AND
EXCELLENT THROUGH THE INCLUSION
OF ALL VOICES.
THE IDEA OF THIS ADDITION TO THE
FOA IS IT WOULD BENEFIT DIVERSE
SCIENTIFIC WORK FORCE TO INCLUDE
FOSTERING SCIENTIFIC INNOVATION
ENHANCING GLOBAL COMPETITIVENESS
CONTRIBUTING TO ROBUST LEARNING
ENVIRONMENTS, IMPROVING THE
QUALITY OF RESEARCH, ADVANCING
THE LIKELIHOOD THAT UNDERSERVED
POPULATIONS PARTICIPATE IN AND
BENEFIT FROM RESEARCH.
THEREFORE ENHANCING PUBLIC
TRUST.
THIS WAS TO BE SUBMITTED AS A
ONE PAGE OTHER ATTACHMENT TO BE
INCLUDED IN GRANT APPLICATIONS
SUBMITTED IN RESPONSE TO
SPECIFIC FOAs.
NIAID IS GOING TO PILOT THIS
TYPE OF AN APPROACH FOR
MULTI-SPECIFIC FOAs.
YOU WILL HEAR FROM ERIC TODAY
ABOUT HOW THIS IS BEING
INCORPORATED INTO THE CFAR AS WE
GET READY TO RENEW THAT
MULTI-DISCIPLINARY,
MULTI-PROJECT FUNDING ACTIVITY.
NEXT SLIDE PLEASE.
SO THE GOALS TO BE DESCRIBED IN
THE PLAN IS TO MAXIMIZE
PARTICIPATION OF INVESTIGATORS
FROM DIVERSE BACKGROUNDS
INCLUDING GROUPS TRADITIONALLY
UNDER-REPRESENTED IN BIOMEDICAL
BEHAVIORAL AND CLINICAL RESEARCH
WORK FORCE SUCH AS
UNDER-REPRESENTED RACIAL ETHNIC
GROUPS THOSE WITH DISABILITIES
DISADVANTAGED BACKGROUNDS IN
WOMEN, ENHANCE DIFFERENT TYPES
OF INSTITUTIONS AND
ORGANIZATIONS, THAT ARE INVOLVED
INCLUDING RESEARCH INTENSIVE
RESEARCH ACTIVE UNDERGRADUATE
FOCUSED MINORITY SERVING AND
COMMUNITY BASED USE OF THE
PROJECT INFRASTRUCTURE TO
SUPPORT CAREER ENHANCING
RESEARCH OPPORTUNITIES.
FOR DIVERSE EARLY MID CAREER
RESEARCHERS CREATE TRAINING AND
MENTORING OPPORTUNITIES
ENCOURAGING PARTICIPATION OF
STUDENTS POST DOCTORAL
RESEARCHERS AND CO-INVESTIGATORS
FROM DIVERSE BACKGROUNDS AND
WHERE APPROPRIATE INCLUDE
COMMUNITY BASED PARTNERS TO
ENSURE ALIGNMENT OF VERGE GOALS
AND ACTIVITIES WITH COMMUNITY
VALUES.
THAT IS A LOT TO THROW AT YOU
BUT IT WAS IMPORTANT TO HAVE
THIS AS A BIG PART OF THE
DIRECTORS REPORT.
MY PLEDGE TO YOU IS THAT AS PART
OF THE DIRECTOR'S REPORT FROM
HERE ON OUT, I WILL HAVE A
SECTION ON DEIA AS PART OF EVERY
DIRECTOR'S REPORT SO IT STAYS ON
OUR RADAR.
AND IT IS BECOMES PARTS OF JUST
WHO WE ARE AND WHAT WE DO AS
PART OF OUR DAILY RESPONSIBILITY
TO ENHANCE AND SUPPORT HIV AND
HIV RELATED RESEARCH.
SO THAT IS THE PLEDGE TO YOU AS
WE MOVE ALONG.
YOU WILL HEAR ABOUT TWO SPECIFIC
ACTIVITIES LATER IN THE TODAY'S
AGENDA AS I SAID BEFORE.
SWITCHING GEARS I WOULD LIKE TO
UPDATE WHERE WE ARE ON COVID
STUDIES.
ACTIVE TOO IN LONG TERM
FOLLOW-UP SAFETY AND EFFICACY
KNOWN TO AGENTS HAVE COME IN,
ACTIV 2D IS AWAITING FDA SIGN
OFF ON A NEW STUDY DESIGN,
HOPEFULLY IT WILL HAVE FIRST
PATIENT IN IN JULY.
ALL US GOVERNMENT SUPPORTED
PHASE 3 SPONSORED STUDIES AND
SAFETY FOLLOW-UP STAGES, FADS
HAD RECOMMENDED A 24 MONTH
SAFETY POSSIBILITY.
THE MODERNA mRNA 1273 VACCINE
HAS BEEN LICENSE FOR 18 AND OVER
AND THE FDA WILL CONVENE --
CONFER A VRBPAC WITHIN THE NEXT
-- BASICALLY WITHIN THE NEXT
NINE DAYS OR SO.
TO LOOK AT THE QUESTION OF EUA
FOR AGES 6 TO 17 AND SIX YEARS
TO SIX YEARS OF AGE DAY LATER.
THE NOVAVAX PROTEIN BASED
VACCINE WILL ALSO BE REVIEWED AT
A VRBPAC TOMORROW.
AS THEY SEEK EUA AUTHORIZATION.
THE SANOFI EUA IS PLANNED FOR
JUNE.
THAT IS WHERE WE ARE WITH MAJOR
ACTIVITIES ON COVID OF THE
DIVISION.
I WOULD LIKE TO CLOSE BY
SPENDING TIME ON OUR ACTIVITIES
RELATED TO ENDING THE HIV
EPIDEMIC WHICH IS A CROSS ALL
PARTS OF HHS ACTIVITY THAT WE
PLAY A ROLE IN THROUGH CURRENTLY
THE CFAR PROGRAM.
YOU WILL RECALL THE GOAL OF THE
THE ENDING THE HIV PANDEMIC IS
TO REDUCE NEW HIV INFECTIONS BY
75% IN FIVE YEARS AND 90% IN IN
TEN YEARS.
IT STARTED WITH A NUMBER OF
TARGETED HIGH BURDEN COUNTIES
AND STATES WITH SUBSTANTIAL
BURDEN YOU CAN SEE BASED ON
WHERE THE STARS AND RED RIBBONS
ARE THAT NIMH AND NIH CENTERS
FOR FUNDED AIDS RESEARCH ARE
WELL-POSITIONED TO BE PLACES
WHERE THERE ARE ONGOING EHE
ACTIVITIES IN PRIORITY
JURISDICTIONS.
SO THE APPROACH WE HAVE TAKEN IS
USING AN INNER AGENCY PROCESS TO
ACCELERATE AND OPTIMIZE THE
EFFECT OF THE IMPLEMENTATION.
SO IT IS FINE FOR NIH TO DESIGN
STUDIES AND BRING THINGS FORWARD
BUT WHAT MAKES OUR SCIENCE
BETTER IS WHEN THIS IS COMMUNITY
ENGAGEMENT AND PARTNERSHIP.
SO TO COLLABORATE WITH CDC AND
HRSA ON IMPLEMENTATION
QUESTIONS, WE CAN GET INNOVATIVE
STRATEGIES BASED ON -- THAT
ADDRESS THE REAL WORLD
CONSTRAINTS AND FACILITATE
ADAPTATIONS FOR THE SPECIFIC
CONTEXT OF MANY OF THE
JURISDICTIONS THAT WHETHER IT IS
A STATE OR LOCAL HEALTH
DEPARTMENT IN COLLABORATION WITH
CDC OR HRSA.
THIS ALLOWS US TO ENHANCE
IMPLEMENTATION RESEARCH
KNOWLEDGE TO CREATE A RESEARCH
BASE AND TO INTEGRATE THESE
RESEARCH ADVANCES INTO CLINICAL
SETTINGS.
THIS ALLOWS US TO SHARE THE
INTERVENTIONS AND STRATEGIES
WITH HIV CARE AND PREVENTION
PROVIDERS.
AND IMPROVE PATIENT OUTCOMES
THROUGH THIS IMPLEMENTATION
PROCESS.
SO IT IS A CYCLE OF DISCUSSION
WITH CDC AND HRSA BRINGING
THINGS FORWARD THAT ARE MUTUALLY
WHEN IMPLEMENTED HELPFUL THROUGH
THE THREE ORGANIZATIONS.
ALSO WORKING WITH COMMUNITY TO
IDENTIFY QUESTIONS OF GENERAL
INTEREST TO THEM.
NEXT SLIDE PLEASE.
IN TERMS OF WHERE THIS THIS IS
IMPLEMENTED, IT IS INTERESTING
TO LOOK AT THE 135 PROJECTS THAT
WE FUNDED THROUGH EHE TODAY,
WHERE THE VAST MAJORITY OF THESE
HAVE BEEN IMPLEMENTED THROUGH A
A COMMUNITY BASED ORGANIZATION,
THE HEALTH DEPARTMENT, MUCH
SMALLER AMOUNTS WITHIN THE
COLLEGE OR UNIVERSITIES, WE HAVE
BEEN ABLE TO ENGAGE FAITH BASED
SPIRITUAL ORGANIZATIONS AND VERY
FEW PRIVATE SECTOR PARTNERS.
PUBLIC PROGRAMS HAVE BEEN PART
OF THIS TOO BUT REALLY HAS BEEN
FOCUSED AT THE COMMUNITY LEVEL
THROUGH CBOs, HEALTH
DEPARTMENTS, FQHCs AND OTHER
COMMUNITY BASED CLINICS.
AND ELIMINATE FROM SCHOOL
SYSTEMS.
NEXT SLIDE PLEASE.
SO HERE ARE THE THEMES THAT WE
HAVE BEEN WORKING ON AND THE
NUMBERS OF PROJECTS PER YEAR YOU
CAN SEE THAT IN FISCAL YEAR 19
WE HAD 65, ONE YEAR PROJECTS
LOOKING AT STRATEGIC
PARTNERSHIPS WORKING WITH
RACIALETH IN MIC MINORITY
POPULATIONS IN 2020 LOOKED AT
SPECIFICALLY TARGETING SIS
GENDER HETEROSEXUAL WOMEN
RELATED TO PREP UPTAKE.
DEVELOPING DATA DRIVEN
COMMUNATION STRATEGIES IN FISCAL
YEAR 21 WE LOOK AT SOCIAL
DETERMINANTS OF HEALTH OF HIV
USING INTERSECTIONAL FRAMEWORK
YOU CAN SEE THE NUMBERS OF
PROJECTS EACH YEAR, HERE IS A
LISTING OF THE EHE ACTIVITIES
THAT WE HAVE SOUGHT TO DEVELOP
PROJECT PROJECTS IN.
WE ARE IN THE PROCESS OF VERY
VIEWING WE WILL ANNOUNCE FUNDING
FOR SUPPLEMENTS SHORTLY BASED IN
THESE FIVE TARGETED AREAS.
FOR 23 AND BEYOND, CONSULTATIONS
WITH CDC AND HRSA IS HOW CAN WE
EXPAND STATUS NEUTRAL APPROACH?
HOW CAN WE DETERMINE HOW BEST
THIS COULD BE IMPLEMENTED SO
DOESN'T MATTER WHETHER LIVING
WITH HIV UNDIAGNOSED OR AT RISK
OF HIV YOU COME INTO A CLINIC,
YOU ARE EVALUATED, YOU RECEIVE
TREATMENT, THE GOAL IS REALLY
USING STATUS NEUTRAL AS WAY OF
BATTLING STIGMA.
WE WANT TO CONTINUE TO MITIGATE
HEALTH RELATED DISPARITIES AND
SPEND TIME AND ENERGY FOCUSING
ON AGING, HIV AND AGING
IMPROVING THE HEALTH OUTCOMES,
AND THE QUALITY OF LIFE OF
PEOPLE AGING WITH HIV.
SO MANY PEOPLE LIVING WITH HIV
ARE OVER 50.
AND AS YEARS PASSED WE HAVE A
GRAYING OF THE HIV PANDEMIC IN
THE UNITED STATES AND WE WANT TO
MAKE SURE THAT PEOPLE CAN LIVE
THEIR BEST LIVES THROUGH PATIENT
CENTERED PERSON CENTERED CARE
BEING IMPLEMENTED THROUGH
CLINICS SO THIS GETS BACK TO THE
HEALTH RELATED QUALITY OF LIFE
QUESTIONS.
SO WE HAVE HAD JOURNAL
SUPPLEMENTS IN SPRING SUMMER
THIS YEAR, WE ARE GOING TO HAVE
ONE WITH 30 ARTICLES REPORTING
FINDINGS FROM EHE PROJECTS.
THERE IS A MEETING SCHEDULED FOR
BIRMINGHAM ALABAMA IN SENT TO
LOOK AT COMMUNITY COLLABORATION
TOWARDS ENDING HIV EPIDEMIC.
THE MEETING OBJECTIVES WHICH ARE
SHARED BEST PRACTICES AND
LESSONS LEARNED. SO THAT WAS
ALL I WAS GOING TO SAY ABOUT
EHE.
SO ONE OF THE THINGS YOU ARE
PROBABLY VERY AWARE OF THAT IS
THAT WE RECEIVE REQUEST AND
RECEIVE PUBLIC COMMENTS AND THIS
CYCLE WE HAVE RECEIVED A NUMBER
OF COMMENTS FROM THE
ORGANIZATION FOR HERPES CURE
ADVOCACY GROUP.
AND THERE ARE PLANS UNDERWAY
BETWEEN NIAID AND CDC TO HOLD A
WORKSHOP IN THE FALL OF 2022 TO
LOOK AT THE STATUS OF THE
RESEARCH CONTROL AND PREVENTION
STRATEGIES, IDENTIFY CHALLENGES
GAPS AND OPPORTUNITIES FOR
FUTURE WORK FOCUSED ON HSV
INFECTION AND DISEASE.
IT IS THE INTENTION OF CDC AND
NIH TO ENGAGE COMMUNITY GROUPS
TO BE PART OF THE MEETING.
AND TO HAVE SECTIONS DEVOTED TO
THEIR QUESTIONS AND NEEDS.
WE ALSO RECEIVED A COMMENT,
AGAIN JUST TO BE CLEAR, THE
CENTER OF GRAVITY ON HERPES
QUESTIONS ARE ON DMID DAIDS IS
AWARE AND WILL PARTICIPATE AS
NEEDED.
BUT THE MEETING IS LARGELY BEING
PLANNED BY COLLEAGUES IN KMID.
WE ALSO RECEIVED A REQUEST TO
MAKE COMPLAINING THAT THE ARAC
MEETING WAS NOT AN OPEN MEETING
WHICH IT IS IN FACT AND THERE
CONTINUES TO BE ONGOING
DISCUSSIONS ABOUT HOW ANIMAL
RESEARCH IS BEINGS CONDUCTED SO
THAT IS THE EXTENT OF THE PUBLIC
COMMENTS FOR THIS CYCLE TO GIVE
A SENSE OF UPCOMING MEETINGS, WE
ARE LOOK AT POTENTIALLY
SEPTEMBER BEING HYBRID.
JANUARY IS VIRTUAL EVEN IF WE
WERE IN FULL OPPORTUNITY WE ARE
CONSIDERING AVRSWG MEETING FOR
THE JANUARY MEETING.
TESTIFY REST OF THE DATES ARE
LISTED THERE FOR YOUR CALENDARS.
I THINK THAT IS IT FOR ME.
I AM AVAILABLE FOR QUESTIONS.
ANY QUESTIONS FOR DR.
DIEFFENBACH.
>> IT WAS GOING TO BE SOMEWHERE
BETWEEN A QUESTION AND COMMENT,
HAPPY TO SEE THE HSV WORK
GETTING SOME ATTENTION.
WITHIN THE INSTITUTE.
THERE IS A RECOGNITION AMONG
WITHIN THIS GROUP HOPEFULLY
SUBSTANTIAL ATTRIBUTABLE RISK
FOR HIV ACQUISITION DUE TO
PRE-EXISTING GENITAL DISEASE FOR
HSV.
THAT IS MORE COMMENT THAN
QUESTION IF THERE IS THAT
RECOGNITION BECAUSE THAT IS AN
IMPORTANT PART OF OUR MISSION AS
WELL.
>> THANK YOU AGAIN.
WE WILL CONTINUE TO WORK CLOSELY
WITH DMID AND THE SDI GROUP
THERE TO ADDRESS THESE
OVERLAPPING AREAS OF INTEREST.
DR. WALLACE, QUESTION.
>> HI CARL.
CURIOUS IF WHAT THE
CONVERSATIONS HAVE BEEN OR IF
THERE IS ANY PROGRESS IN
CONVERSATIONS TO ENGAGE
HISTORICALLY BLACK COLLEGES,
HISTORICALLY BLACK MEDICAL
SCHOOLS AND OTHER MINORITY
SERVING ORGANIZATIONS BASED TON
SLIDE YOU PUT UP ABOUT ENGAGING
DIVERSE GROUPS AND RESEARCH AND
BUILDING OUT THAT CAPACITY.
>> SO WITHIN THE INSTITUTE THERE
ABSOLUTELY HAS BEEN WE HAVE
BROUGHT IN SEVERAL MEDICAL
SCHOOLS TO BE PART OF CO-VPN AND
THOSE ACTIVITIES HAVE CONTINUED
LARGELY THROUGH DMID GROUP THE
IDCRC CONTINUES TO MAINTAIN
LINKAGES TO BRING THOSE GROUPS
WITHIN A LARGER CLINICAL TRIALS
FRAMEWORK THAN IS AVAILABLE FOR
WHERE WHAT CURRENTLY DOING
WITHIN THE DIVISION OF AIDS SO
THERE IS SHARING ACROSS THE
INSTITUTION AND MAKING SURE THAT
WHICH ARE GIVING ORGANIZATIONS
OPPORTUNITIES COMMENSURATE WITH
AND CAN GROW WITH THEIR
POTENTIAL.
>> THANK YOU, DR. DIEFFENBACH.
WE WILL KEEP MOVING, VERY NICE
REPORT.
IT IS A PLEASURE NOW FOR ME TO
INTRODUCE WELCOME DR. MAUREEN
GOODENOW WHO AS YOU KNOW IS THE
DIRECTOR OF OFFICE OF AIDS
RESEARCH.
WHO WILL BE GIVING US AN UPDATE.
THANK YOU, DR. GOODENOW.
>> THANK YOU VERY MUCH FO FOR TE
OPPORTUNITY TO PROVIDE RESEARCH
AND UPDATES ON OFFICE OF OHOR.
PARTICULARLY WITH EXPANSION OF
THE WORK FORCE.
I UNDERSTAND CENTRALLY IS
WORKING THE SLIDES.
I WILL LET YOU FOE WHEN I NEED
TO CHANGE.
AS AN EXOFFICIO MEMBER OF ARAC,
HAPPY TO DISCUSS THE ROLE OF OAR
WITH YOU.
IN FACT THIS PRESENTATION IS
PART OF THE ONGOING STRATEGY TO
SHARE OAR PERSPECTIVES WITHIN
NIH INSTITUTES CENTERS AND
OFFICES AND THEIR COUNCILS MORE
BROADLY.
MY REMARKS WILL FOCUS ON TWO
AREAS WHICH THE NIH OAR
INFLUENCES THE HIV RESEARCH WORK
FORCE, FIRST THE OAR LISTENING
SESSIONS AND THE SECOND OAR
INITIATIVES THAT SUPPORT EARLY
CAREER INVESTIGATORS WITH A
FOCUS ON DIVERSITY THE OAR IS
EMBEDDED WITHIN OFFICE OF THE
NIH DIRECTOR.
WAS ESTABLISHED BY CONGRESS
NEARLY 35 YEARS AGO.
BY LEGISLATION THAT DEFINE THE
ACTIVITY ROLES AND
RESPONSIBILITIES FOR THE OFFICE.
THE OAR DIRECTOR IS APPOINTED BY
THE HHS SECRETARY AND REPORTS AS
THE ASSOCIATE DIRECTOR FOR AIDS
RESEARCH TO THE NIH DIRECTOR.
HIV RESEARCH FUNDING COMPRISES
7% OVERALL HIV BUDGET AND
CURRENTLY TOTALS CLOSE TO
$3.2 BILLION ANNUALLY.
OAR'S RESPONSIBLE FOR THE
ALLOCATION TRACKING AND
REPORTING OF THE NIH HIV FUNDING
ACROSS INSTITUTE CENTERS AND
OFFICES OR ICOs AND DEFINING
THE NIH STRATEGIC PLAN FOR HIV
AND HIV RELATED RESEARCH.
OAR PRIORITY ACTIVITIES ARE
ORGANIZED BY FOUR KEY FUNCTIONS.
TO CONVENE CATALYZE COORDINATE
AND COMMUNICATE HIV RELATED
RESEARCH ACROSS THE NIH.
CENTRAL TO ALL THESE ACTIVITIES
IS THE NEED TO ENSURE DIVERSITY
AND INCLUSIVITY AND COMBAT
RACISM IN ALL ITS FORMS TO
ENSURE THE SUSTAINED SUCCESS OF
THE NIH HIV RESEARCH ENTERPRISE
THE NIH UNITE INITIATIVE IS
AGENCY WIDE EFFORT TO IDENTIFY
AND ADDRESS STRUCTURAL RACISM
WITHIN BIOMEDICAL RESEARCH AND
BOLSTER EFFORTS OF HIV OFFICES
INVOLVED IN DIVERSITY EQUITY
INCLUSION AND ACCESSIBILITY.
IMPORTANTLY NIH OAR WORKS
CLOSELY WITH OTHER HHS AGENCIES
TO CARRY OUT THE MISSION WITH
INPUT AND GUIDANCE FROM THE OAR
ADVISORY COUNCIL OR OARAC AND
YOU HAVE BEEN INTRODUCED TO DR.
JONAS SASHA HERE AS INCOMING
REPRESENTATIVE FROM OARAC T TO
ARAC.
THE OARAC AND OTHER HIV
ACTIVITIES CONDUCTED OR
SUPPORTED BY THE NIH.
O OARAC'S HINNIES NIH OFFICE OF
DIRECTOR CDC VETERANS
ADMINISTRATION AND DEPARTMENT OF
DEFENSE.
WHILE OTHER EXOFFICIOS REPRESENT
COUNSELS OF NIH ICs, WITH
LARGEST PROPORTION OF HIV
FUNDING AND THAT INCLUDES NIAID
WITH DR. CARL DIEFFENBACH, NIDA,
NCI NIMH AND NICHD.
THESE EXOFFICIO MEMBERS INFORM
INFORM AND FACILITATE ACTIVITIES
WITHIN THE NIH AND ACROSS OTHER
US GOVERNMENT AGENCIES AND THE
REPRESENTATION HELPS ENSURE THE
APPROPRIATE BREADTH AND DEPTH OF
NIH HIV RESEARCH PORTFOLIO. IN
THE NEXT SLIDES THE OFFICE OF
AIDS RESEARCH WORKS ACROSS THE
NIH ICOs TO ADVANCE RESEARCH
TO ENDS THE HIV EPIDEMIC IMPROVE
HEALTH OUTCOMES FOR PEOPLE WITH
HIV AND ENSURE RESEARCH FUNDING
IS DIRECTED AT HIGHEST PRIORITY
AREAS TO DO THIS EACH ICO WITH
HIV PORTFOLIO HAS A COORDINATOR.
APPOINTED BY THE RESPECTIVE
INSTITUTE CENTER OFFICE
DIRECTOR.
AND THE COORDINATOR SERVES ON
THE NIH HIV AIDS EXECUTIVE
COMMITTEE.
THE NAC PROVIDES A FORUM FOR OAR
AND OTHER CONSTITUENTS TO WORK
TOGETHER TO SYNERGIZE HIV
RESEARCH ACROSS THE AGENCY.
AND I WOULD LIKE TO TAKE THIS
OPPORTUNITY TO THANK ROB PALMER
AND THE REST OF THE NIAID DAIDS
TEAM FOR THEIR WORK WITH US ON
THE NAC.
THE NAC INCLUDES SEVERAL WORKING
GROUPS THAT FACILITATE
COLLABORATION SUCH AS ENDI EN EE
HIV EPIDEMIC THAT CARL MENTIONED
AND THE, WHOING GROUP TO SUPPORT
EARLY CAREER INVESTIGATORS IN
HIV.
SIMILAR NIH WIDE COORDINATION
EFFORTS ORIGIN GNAT MULTIPLE
EFFORTS AND WAYS ACROSS THE NIH
AND ONE OF THESE EXAMPLES IS THE
NIH CFAR STEERING COMMITTEE
WHICH INVOLVES ALL ICOs THAT
SUPPORT THE CFAR PROGRAM.
IN THE NEXT SLIDE, IS SHOWN THE
DISTRIBUTION OF FISCAL YEAR 2021
HIV FUNDING ACROSS THE NIH
INSTITUTES AND CENTERS.
THERE IS A CLEAR RANGE IN TERMS
OF TOTAL FUNDING LEVELS FROM
ACROSS THE TOP MORE THAN
1.6 BILLION OF 3.2 BILLION FOR
NIAID RANGING DOWN TO A FEW
MILLION FOR SOME OF THE OTHER
ICs.
THERE ARE ALSO DIFFERENCES IN
MAG INSTITUTES OF HIV FUNDING
RELATIVE TO ICOs TOTAL FUNDING
SO THE DARKER SHADES REPRESENT
ICs WITH LARGER PROPORTIONAL
HIV RESEARCH FUNDING.
SO NIAID, THEIR HIV RESEARCH
FUNDING REPRESENTS AT LEAST A
THIRD OF THEIR TOTAL NIH
FUNDING.
FOR OTHER ICs HIV FUNDING
REPRESENTS GENERALLY SOMEWHERE
BETWEEN 2 TO 20% OF THEIR
OVERALL NIH RESEARCH ALLOCATION
IN THE NEXT SLIDE WHICH CARL HAS
SHOWN YOU, THE NIH RESEARCH
PRIORITIES REQUIRE A
MULTI-INSTITUTE
MULTI-DISCIPLINARY APPROACH THAT
ALIGNS WITH NIH HIV RESEARCH
PRIORITIES AND IN PARTICULAR,
THE CROSS CUTTING AREAS OF
RESEARCH REPRESENTED BY THE
WHITE CIRCLES, INCLUDE RESEARCH
TRAINING, INFRASTRUCTURE, AND
WORK FORCE CAPACITY BUILDING.
WHICH I WILL TALK MORE ABOUT
NOW.
IN THE NEXT SLIDE OAR CONTINUES
TO ORGANIZE FORMAL LISTENING
SESSIONS TO HEAR DIRECTLY FROM
DIVERSE STAKEHOLDERS.
SINCE 2018 OAR HELD MORE THAN 60
COMETSIC LISTENING SESSIONS AND
COMMUNITY ENGAGEMENTS AT THE
LOCATIONS INDICATED BY THE RED
CIRCLES IN THIS MAP.
AND YOU HAVE ALREADY SEEN
ANOTHER VERSION OF THIS MAP FROM
CARL WHICH INDICATED THE
JURISDICTIONS FOR EHE AS WELL AS
LOCALIZATION OF CENTER FOR AIDS
RESEARCH AND THE NIMH AIDS
RESEARCH.
MANY LOCATIONS IN THE WILL BEING
SESSIONS OVERLAPPED WITH THE EHE
JURISDICTIONS, WITH RURAL
COMMUNITIES WITH HIGH HIV BURDEN
OR WITH KEY HIV STAKEHOLDER
ORGANIZATIONS.
OAR DEVELOPED A STAKEHOLDER
OUTREACH AND ENGAGEMENT REPORT
THAT IS AVAILABLE ON OUR
WORKSHOP ON OUR WEBSITE. AND
THIS REPORT DETAILS KEY THEMES
FROM IN PERSON LISTENING
SESSIONS HELD BETWEEN 2018
THROUGH EARLY 2020.
LISTENING SESSIONS SHIFTED TO A
VIRTUAL PLATFORM IN 2022, AS A
RESULT OF COVID.
AND A SUMMARY OF THESE VIRTUAL
SESSIONS HAS JUST BEEN CLEARED
AND WILL BE AVAILABLE ON THE OAR
WEBSITE IN THE NEXT TWO WEEKS.
IMPORTANTLY, IN EVERY LISTENING
SESSION WITH ACADEMIC PARTNERS
PARTICIPANTS UNDERSCORED THE
NEED TO ENHANCE THE PIPELINE OF
EARLY AND MID CAREER HIV
INVESTIGATORS AND ENSURE DIVERSE
-- DIVERSITY AND INSTITUTIONAL
CAPACITY TO CONDUCT CUTTING EDGE
RIGOROUS SCIENTIFIC RESEARCH.
IN THE NEXT SLIDE AS NOTED THE
OAR DEVELOPS THE NIH STRATEGIC
PLAN FOR HIV AND HIV RELATED
RESEARCH.
THE CURRENT PLAN COVERS FISCAL
YEARS 2021 THROUGH 2025 AND
FEATURES FOUR STRATEGIC GOALS.
IN IN PARTICULAR STRATEGIC FOUR
GOAL STATES BUILD HUMAN RESOURCE
AND INFRASTRUCTURE CAPACITY TO
ENHANCE SUSTAINABILITY OF HIV
RESEARCH DISCOVERY AND THE
IMPLEMENTATION OF FINDINGS BY
DIVERSE AND MULTI-DISCIPLINARY
WORK FORCE.
TO IMPLEMENT STRATEGIC GOAL 4
OAR LAUNCHED A NUMBER OF
ACTIVITIES TO SUPPORT THE HIV
RESEARCH WORK FORCE.
FOR EXAMPLE IN FY 21 WE
FACILITATED A SERIES OF
ADMINISTRATIVE SUPPLEMENTS TO
SUPPORT COLLABORATIVE HIV
RESEARCH AT NATIONAL INSTITUTES
OF MINORITY HEALTH AND HEALTH
DISPARITY RESEARCH CENTERS IN
MINORITY INSTITUTES AND WE JUST
TALKED A LITTLE BIT ABOUT THE
RCMIs.
THIS INITIATIVE WAS CO-FUNDED BY
NIMHD AND THE HHS MINORITY HIV
AIDS FUND.
OTHER EFFORTS TO SUPPORT
DIVERSITY AND INCLUSION STEM
FROM PROGRAMS SUCH AS THE
MENTORING PROGRAM FOR NEW HIV
AIDS INVESTIGATORS TO MEET THE
NEEDS OF HISPANIC LATINO
COMMUNITIES AS WELL AS THE C FAR
DIVERSITY EQUITY AND INCLUSION
PIPELINE INITIATIVE THAT AIMS TO
INCREASE NUMBER OF UNDERSTOOD
REPRESENTED MINORITIES AND
TRAINEES ENGAGED IN HIV SCIENCE
FROM HIGH SCHOOL TO
POST-DOCTORAL LEVELS.
OAR CONVENED INPUT ACROSS NIH
ICOs TO UPDATE OBJECTIVES AND
IMPLEMENTATION PLANS TO THE
WHITE HOUSE NATIONAL HIV AIDS
STRATEGY.
THIS INCLUDED ADDING EXPANSION
AND DIVERSIFICATION OF THE
RESEARCH WORK FORCE AS WELL AS
THE TOPICAL RESEARCH AREAS OF
HIV CURE, INTERVENTION
DEVELOPMENT, IMPLEMENTATION
STIGMA AND DISPARITIES.
IN THE PAST TWO YEARS NIH OAR
CONDUCT SYSTEMATIC STEP WISE
APPROACH EFFORT TO SUPPORT HIV
EARLY CAREER INVESTIGATORS WITH
A FOCUS ON DIVERSITY, ACTIVITIES
I INCLUDE PORTFOLIO ANALYSIS I
WILL DESCRIBE SHORTLY AND FOUR
LISTENING SESSIONS TO UNDERSTAND
ISSUES AFFECTING HIV
RESEARCHERS.
SOME OF THE THEMES THAT EMERGED
INCLUDED DIVERSITY MENTORING
PEER REVIEW, FUNDING MECHANISMS
NETWORKS, AND COVID-19.
OAR CONVENED A PANEL OF 19
SENIOR HIV INVESTIGATORS AND
EXPERIENCED MENTORS FROM DIVERSE
ACADEMIC INSTITUTIONS, TO
PARTICIPATE IN AN EXPERT
CONSULTATION PATTERN EXPERT
CONSULTATION PANEL.
AND REPORT SUMMARIZES IS IN
CLEARANCE AND WILL BE POSTED TO
OUR WEBSITE.
NO RESPONSE TO INPUT RECEIVED
THE NIH OAR DEVELOPED EARLY
CAREER INVESTIGATOR YOU CAN SEE
A SCREEN SHOT ON THE RIGHT SIDE
OF THE SLIDE.
TO CENTRALIZE RELEVANT
INFORMATION FOR INVESTIGATORS
AND PROVIDE EASY ACCESS TO ONE
PLACE TO GRANT OPPORTUNITIES AND
OTHER RESOURCES. THE NEXT SLIDE
IS THREE OF THESE KEY STEPS.
IT SHOULD BE THE ESI AWARDEES
NIH OVERALL VERSUS NIH HIV.
IN 2020 AND 2021, OAR CONDUCTED
A PORTFOLIO ANALYSIS OF EARLY
STAGE INVESTIGATORS.
ACROSS THE NIH ENTERPRISE THERE
WAS A 50 PERCENT INCREASE IN
NUMBER OF NEW RESEARCHERS FROM
900 IN 2017 TO ALMOST 1400 IN
2020.
SINCE INCEPTION OF NEXT
GENERATION RESEARCH INITIATIVE.
THIS IS THE TOP BLUE LINE ON
THIS.
ON THE LEFT-HAND SIDE OF THE
GRAFT IN GRAY SHADING ARE LEVELS
OF EARLY STAGE INVESTIGATOR
AWARDEES PRE AND NGRI AND THEN
STARTING ON RIGHT HAND SIDE POST
NGRI.
THE 2020 ESI AWARDS ACROSS THE
NIH REPRESENT ABOUT 5% OF THE
TOTAL RO1 FUNDING AT THE NIH.
IN CONTRAST RED LINE ACROSS
BOTTOM FROM 2017 TO 2019 NUMBER
OF HIV FOCUSED ESI RECEIVING
FIRST GRANTS WAS STABLE AT 45.
THIS REPRESENTS APPROXIMATELY 3
PERCENT OF TOTAL HIV RO1 AWARDS.
IN 2020, OAR INCREASED THE
NUMBER OF HIV ESI AWARDEES BY
NINE.
THAT IS SHOWN IN THE CIRCLE AT
THE FAR RIGHT OF THE GRAPH.
TO MAINTAIN THE AVERAGE OF 45
AWARDEES. WITHOUT OAR ACTION
THAT NUMBER WOULD HAVE BEEN 36
AS SHOWN ON THE SLIDE.
CURRENT EFFORTS ARE AN
IMPROVEMENT A SUSTAINABILITY
PLAN IS NEEDED TO MAINTAIN AND
INCREASE NEXT GENERATION OF HIV
INVESTIGATORS.
IN THE NEXT SLIDE, ON APRIL OF
THIS YEAR OAR CONVENED THE FIRST
WORKSHOP FOR EARLY CAREER
INVESTIGATORS IN HIV AIDS.
THE WORKSHOP AIMED TO STIMULATE
SCIENTIFIC EXCHANGE NETWORKING
COLLABORATION, FACILITATE
INTERACTIONS AND INCREASE
FAMILIARITY ABOUT THE NIH REVIEW
AND FUNDING PROCE PROCESSES.
IN THE NEXT SLIDE, THE NIH OAR
WILL PRIORITIZE AND SUPPORT
DIVERSE HIV RESEARCH WORK FORCE.
BASED ON THE TREMENDOUS INTEREST
IN THE FIRST HIV ECI WORKSHOP WE
PLAN TO COORDINATE WITH THE NAC,
ADDITIONAL EVENTS EARLY CAREER
HIV INVESTIGATORS.
AND CONTINUE TO UPDATE THE
WEBSITE WITH TIMELY RELEVANT
RESOURCES.
WE WILL CONTINUE TO MONITOR AND
SUPPORT IMPLEMENTATION OF
RESEARCH WORK FORCE OBJECTIVES
OF THE NHAS AS WELL AS NIH UNITE
INITIATIVEMENT IN THE NEXT SLIDE
NEXT OARAC MEETING WILL BE HELD
IN A FEW WEEKS JUNE 23, NOON TO
4:30.
IT IS A LIVE OPEN VIDEO CAST
MEETING.
AND THE AGENDA WILL FEATURE
UPDATES FROM NUMBER OF
INTERAGENCY PARTNERS.
IN THE FINAL SLIDE I WOULD LIKE
TO THANK THE OAR TEAM FOR
LEADING THE EFFORTS THROUGH THE
NEXT GENERATION HIV
INVESTIGATORS, PARTICULARLY DR.
LIZ TAYLOR AND MELISSA OMARA.
THANK YOU VERY MUCH, HAPPY TO
ANSWER ANY QUESTIONS.
>> THANK YOU, DR. GOODENOW FOR
THE OVERVIEW AND GREAT
COMMITMENT TO NGRI TO ENHANCING
DIVERSITY IN THE WORK FORCE.
LET'S TAKE TIME FOR A QUESTION
OR TWO.
>> MAYBE WE CAN TURN THE SLIDES
OFF
>> THANK YOU SO MUCH.
THOSE ARE SO GREAT.
REALLY FASCINATED BY THE
CIVILITY PLEDGE BECAUSE I THINK
EVERYONE NEEDS TO BECOME SO
CIVIL, EVERYONE IS SUCH A MESS
WITH THE PANDEMIC.
SO I THINK THAT IS A REALLY
INTERESTING THING TO SEE AND
TAKE FROM NIH WHO RECEIVES NIH
FUNDING IT FEELS STRONGLY WE
SHOULD BE TAKING A PROFESSIONAL
PLEDGE.
THE ONE THING I WANT TO ASK
ABOUT THE DIVERSITY IS I AM
SEEING A REAL COMMITMENT FROM
THE NIH AND OFFICE OF AIDS
RESEARCH ABOUT THIS ENCOURAGING
DIVERSE PARTICIPANTS IN
RESEARCH.
BUT I HAVE ALSO SEEN, THIS IS
SPECIFIC FROM INFECTIOUS
DISEASE, THAT BIOMEDICAL
DEPLETED, PEOPLE ARE FEELING
DISILLUSIONED AFTER THE PANDEMIC
AND THE PANDEMIC AND I DON'T SEE
OUR PIPELINE FOR INFECTIOUS
DISEASE FELLOWS GOING DOWN AND
THE DERAILMENT OF THEIR OWN
RESEARCH DURING THE COVID
PANDEMIC.
PEOPLE ON Ts AND Ks.
SO WE HAVE MADE GREAT EFFORTS
LIKE INCREASING THE PAY LINE FOR
K 23 AT NIAID AND KO 8 WHICH IS
AMAZING.
BUT I THINK STRESSING OF THE
INCREASING SUPPORT FOR CFARS
WHICH DEVELOP EARLY STAGE
INVESTIGATORS BUT THE DIVERSITY
ASPECT IS PUTTING MONEY LIKE
DESIGNATED MONEY TO PEOPLE WHO
ARE DIVERSE.
AND I KNOW WE WILL TALK ABOUT
THAT.
BUT LITERALLY DESIGNATED GRANTS
AS MUCH AS YOU CAN WITHIN THE
PARAMETERS OF THE LAW THAT ARE
SPECIFICALLY FOR URMs.
>> I WILL SAY SOMETHING ABOUT
THAT, MONICA, WE AGREE.
AND THE NEXT INITIATIVE ON THE
BOOKS THAT WE WILL HEAR ABOUT
TODAY REPRESENTS NIAID WIDE
EFFORT TO SPECIFICALLY ADDRESS
THIS POINT.
WE HAVE BEEN TALKING AS JUST THE
DAIDS INITIATIVE BUT WE FELT IT
WAS EXTREMELY IMPORTANT WE MAKE
THIS NIAID WIDE ACTIVITY.
BECAUSE IT IS NIAID WIDE THAT IS
WHY LESHAWNDRA WILL TALK ABOUT
THIS FROM THE STANDPOINT OF THE
INSTITUTE.
THE KEY WORDS YOU SAID THERE
WITHIN THE LIMITS OF THE LAW.
WE HAVE -- WE ALL DO THE BEST WE
CAN AND THERE ARE THINGS THAT
ARE LAW AND THAT ARE GUIDELINES
AND GUIDELINES ARE MEANT TO BE
NOT BROKEN BUT BENT.
WE WILL FIND WAY.
CFARS CONTINUES TO BE MASSIVE
SOURCE OF INNOVATION, YOU WILL
HEAR ABOUT THAT FROM ERIC AND
NETWORKS HAVE CONTINUED TO BE
SOURCE OF TRAINING MINORITY
INVESTIGATORS.
THE BIGGEST PROBLEM WE HAVE THIS
IS MY SPEECH, WE ARE LATE IN THE
PIPELINE.
WE ARE AT THE END.
WITH C FARES STARTED TO DO IS
MOVE HIGH SCHOOLS AND THAT IS
CRITICAL FOR US FOR THE FUTURE.
>> DR. AGARWAL.
>> I WANTED TO FOLLOW-UP ON THAT
I HAD MADE IN THE CHAT, YOU MAY
ALREADY BE AWARE OF THE PROGRAM
THE OFFICE OF DATA SCIENCE
LAUNCHED ON ENHANCING RESEARCH
DIVERSITY AND PARTICIPATION IN
THE AI WORK FORCE M. WONDERING
IF THAT MODEL IS SOMETHING TO
CONSIDER, PERHAPS VARIANT TO THE
POINT MADE EARLIER ABOUT THE
INVOLVEMENT OF HBCUs, STEPHAN
SAID THAT DR. DIEFFENBACH'S
POINT REACHING OUT TO PEOPLE
VERY EARLY IN THEIR CAREERS, THE
SAME INITIATIVE IS TARGETED
DOING EXACTLY THAT, SOMETHING TO
EXPLORE.
>> NO DOUBT.
>> GREAT.
LAST QUESTION, DR. (INAUDIBLE).
>> HI, THERE.
SO THIS IS MORE A GREEDY
QUESTION.
THINKING ABOUT CDC BUT ARE YOU
USING ANY TOOLS TO LOOK AT
FUNDING OPPORTUNITIES LIKE
EQUITY OR DIVERSITY -- THIS
ASSESSMENT OF WHAT GOES OUT THE
DOOR?
>> WE HAVE DONE THAT.
AND IT IS ABYSMAL.
>> THANK YOU.
>> IN A WORD, HENCE THE REASON
WHY WE WANT TO DO SOME THINGS
THAT ARE REALLY FOCUSED AND
TARGETED.
AND CONTINUE TO DO WHAT WE CAN
TO FIX THE REST OF IT.
>> THANK YOU VERY MUCH.
I WANT TO POINT OUT THAT PEOPLE
WHO ARE INTERESTED IN MORE
INFORMATION, I SEE DR. AGARWAL
PUT IN THE CHAT ABOUT OFFICE OF
DIVERSITY -- STRATEGIC SCIENCE,
AND THE ADVISORY COUNCIL FOR THE
NIH DIRECTOR IS MEETING THIS
WEEK THURSDAY AND FRIDAY AND
THERE WILL BE DISCUSSION ABOUT
UNITE PROGRAM AS WELL AS REPORT
OUT AS FAR AS I KNOW FROM THE
OFFICE OF DATA SCIENCE STRATEGY.
IN AUCTION AT THE OARAC MEETING
LATER IN THE MONTH THE DIRECTOR
OF ODSS SUSAN GREGARICK WILL BE
PRESENTING AT THE OARAC MEETING.
>> THANK YOU VERY MUCH, DR.
GOODENOW.
APPRECIATE IT.
DR. DIEFFENBACH, YOU WANT TO
INTRODUCE DR. PRICE?
>> I WOULD LIKE Y'ALL TO WELCOME
A GUEST PRESENTER TODAY, DR.
LESHAWNDRA PRICE, DIRECTOR OF
THE NIAID OFFICE OF RESEARCH
TRAINING SPECIAL PROGRAMS WITHIN
DEA.
OR DIVISION OF EXTRAMURAL
ACTIVITIES.
AGAIN, THRILLY SHAN DRAW'S
EFFORTS WORKING WITH ERIC AND
TEAM AND WORKING WITH US AND THE
OTHER DIVISIONS IS PRESENTING
THIS FOR THE WHOLE OF NIAID.
OUR DIVISION WAS CHOSEN TO HAVE
THIS CLEAR THIS COUNCIL BECAUSE
WE FELT IT WAS A REALLY GOOD
OPPORTUNITY FOR US IN DIVISION
OF AIDS TO HIGHLIGHT KINDS OF
THINGS WE CAN DO AS AN
INSTITUTE.
SO I WILL TURN IT OVER TO
LESHAWNDRA TO PRESENT THE
INITIATIVE.
>> THANKS VERY MUCH, THANKS FOR
THIS OPPORTUNITY TO SHARE A NEW
NIAID WIDE CONCEPT FOR APPROVAL
TO ENHANCE WORK FORCE DIVERSITY
THROUGH SUPPORT OF NEW AT RISK
INVESTIGATORS.
I WANT TO THANK COLLEAGUES FROM
DAIDS INCLUDING ERIC FOR
DEFINING THE CONCEPT AND
ASSISTING WITH THE PRESENTATION.
THE GOAL OF THE PROPOSED
INITIATIVE IS TO PROVIDE
INDEPENDENT RESEARCH SUPPORT IN
ALL NIAID MISSION AREAS TO
SUPPORT NEW INVESTIGATORS, EARLY
STAGE INVESTIGATORS, AND AT RISK
INVESTIGATORS FROM DIVERSE
BACKGROUNDS.
AS DEFINED BY THE NIH INTEREST
IN DIVERSITY.
YOU WILL RECALL NEW
INVESTIGATORS ARE DEFINED THOSE
WHO NOT COMPETED SUCCESSFULLY
FOR SUBSTANTIAL NIH INDEPENDENT
FUNDING AND ESIs SUB SETS OF
NEW INVESTIGATORS, ARE THOSE WHO
ARE WITHIN TEN YEARS OF TERMINAL
RESEARCH DEGREE OR ENDS OF POST
GRADUATE CLINICAL TRAINING.
YOU MAY BE LESS FAMILIAR WITH AT
RISK INVESTIGATORS.
AT RISK INVESTIGATORS HAD PRIOR
SUPPORT AS PIs ON A
SUBSTANTIAL RESEARCH AWARD AND
UNLESS SUCCESSFUL AND SECURING A
SUBSTANTIAL RESEARCH GRANT AWARD
IN THE CURRENT FISCAL YEAR WILL
HAVE NO SUBSTANTIAL RESEARCH
FUNDING AND THE FOLLOWING FISCAL
YEAR.
THE PROPOSED INITIATIVE WILL USE
THE RO1 MECHANISM AND APPLICANTS
REQUEST AWARDS UP TO FIVE YEARS
OF THE SUPPORT.
WE ANTICIPATE 20 TO 50
APPLICATIONS EACH YEAR AND
EXPECT TO MAKE 12 TO 18 AWARDS
ANNUALLY.
FIRST YEAR COSTS FOR THE
INITIATIVE ARE EXPECTED TO BE
APPROXIMATELY $9 MILLION AND OF
THAT 9 MILLION, 4 MILLION WILL
BE FOR AIDS RESEARCH.
THE LAST SEVERAL YEARS HAVE
BROUGHT MORE ATTENTION TO WHY
DIVERSITY MATTERS IN BIOMEDICAL
RESEARCH.
STUDIES HAVE NOT ONLY SHOWN THE
QUALITY OF RESEARCH INCREASES
WHEN PERFORMED BY DIVERSE GROUPS
AND DIFFERENT LIFE EXPERIENCES
ADD VALUABLE PERSPECTIVES TO
RESEARCH PROJECTS BUT ALSO SUCH
TEAMS TEND MORE CREATIVE AND
INNOVATIVE.
WE ASK ALL KINDS OF DIFFERENT
RESEARCH QUESTIONS IN SCIENCE
AND ESPECIALLY IN THE RESEARCH
SUPPORTED BY NIAID.
ASKING QUESTIONS DRIVE SCIENCE
FORWARD AND RESEARCHERS WITH
DIFFERENT PERSPECTIVES ASK
DIFFERENT QUESTIONS PROPELLING
US IN DIRECTION OF BOLD ADVANCES
IN SCIENCE.
IT IS ALSO IMPORTANT TO REMEMBER
THAT WE THE NIH SERVE THE PEOPLE
OF THE U.S. WE ASPIRE TO SUPPORT
A RESEARCH WORK FORCE THAT
REFLECTS SOCIETY AND IS NOT
DISPROPORTIONATELY WEIGHTED TO
ONE GROUP OR ANOTHER.
IN RECENT YEARS TOPIC OF
DIVERSIFYING THE, WHO FORCE
BECOME A MORE CENTRAL PRIORITY.
IT DOESN'T MEAN WE ARE YET
SUCCEEDING, LONG TERM COMMITMENT
IS NEEDED TO ACHIEVE AND SUSTAIN
DIVERSITY AND EQUITY, IN THE
BIOMEDICAL WORK FORCE.
NEXT SLIDE PLEASE.
ALIGNED WITH THE NIH, NIAID
RECOGNIZES THE IMPORTANCE OF
ADDRESSING SCIENTIFIC WORK FORCE
DIVERSITY TO ENSURE WE HAVE A
POOL OF HIGHLY TALENTED
SCIENTISTS FROM DIVERSE
BACKGROUNDS CAPABLE OF
FURTHERING ARE OUR MISSION.
THIS PROPOSED INITIATIVE IS
ALIGNED WITH THE NEXT GENERATION
RESEARCHERS INITIATIVE ENACTED
THROUGH THE 21ST CENTURY CURES
ACT.
WHICH IS AN INTENDED TO PROMOTE
AND PROVIDE OPPORTUNITIES FOR
NEW RESEARCHERS AND EARLY
RESEARCH INDEPENDENCE AND
ENHANCE WORK FORCE DIVERSITY.
SIMILARLY, THE INITIATIVE IS
CONSISTENT WITH THE NIH INTEREST
IN DIVERSITY IN THAT INDIVIDUALS
FROM UNDER-REPRESENTED GROUPS
WILL BE STRONGLY ENCOURAGED TO
WORK WITH THEIR ORGANIZATIONS TO
APPLY FOR NIH SUPPORT.
THESE POPULATIONS INCLUDE
INDIVIDUALS FROM RACIAL ETHNIC
GROUPS THAT HAVE BEEN SHOWN TO
BE UNDER-REPRESENTED IN HEALTH
RELATED SCIENCES ON A NATIONAL
BASIS AND UNDER-REPRESENTED AND
BIOMEDICAL RESEARCH, INDIVIDUALS
WITH DISABILITIES, INDIVIDUALS
FROM DISADVANTAGED BACKGROUNDS
MEETING CERTAIN CRITERIA.
AND WOMEN AS OUTLINED IN THE NIH
INTEREST IN DIVERSITY.
THE INITIATIVE ALSO IS THE NIH
STRATEGIC PLAN FOR HIV AND HIV
RELATED RESEARCH AS DR. GOODENOW
PREVIOUSLY MENTIONED AND THE
NATIONAL HIV AIDS STRATEGY WHICH
SPECIFICALLY ENCOURAGES TRAINING
AND EXPANSION OF DIVERSE HIV
WORK FORCE BY FURTHER DEVELOPING
AND PROMOTING OPPORTUNITIES TO
SUPPORT THE NEXT GENERATION OF
HIV PROVIDERS INCLUDING
RESEARCHERS AND OTHERS FROM
UNDER-REPRESENTED POPULATIONS.
AND DR. DIEFFENBACH MENTIONED
THIS EARLIER AS WELL.
NEXT SLIDE PLEASE.
THE NIH HAS A LONG HISTORY OF
FUNDING PROGRAMS TO ENHANCE
DIVERSITY PARTICULARLY AT THE
LEVEL OF INDEPENDENT SCIENTISTS
AND WITHIN SCIENTIFIC LEADER
LEADERSHIP.
SINCE THE GINTHER REPORT TEN
YEARS AGO THE NIH IS WORKING TO
NARROW DISPARITIES IN FUNDING.
IN RECENT YEARS THERE'S BEEN
SOME ENCOURAGING TRENDS
INCLUDING AN INCREASE IN NUMBER
OF RO1 APPLICATIONS, SUBMITTED
TO THE NIH AND A MODEST INCREASE
IN FUNDING RATES FOR
UNDER-REPRESENTED GROUPS.
RESEARCHERS FROM
UNDER-REPRESENTED GROUPS HOWEVER
HAVE BEEN AND CONTINUE TO BE
SUBSTANTIALLY UNDER-REPRESENTED
IN THE BIOMEDICAL RESEARCH WORK
FORCE AND THE NIH EXTRAMURAL
RESEARCH PORTFOLIO.
DISPARITIES REMAIN AND WE STILL
HAVE A LONG WAY TO GO.
NIAID HAS LONG BEEN A LEADER IN
WORK FORCE DIVERSITY FROM OUR
TECHNICAL ASSISTANCE WORKSHOPS
TO SUPPORT FOR TRAINEES AND
EARLY CAREER INVESTIGATORS.
AND MANY YEARS AGO NIAID PILOTED
TWO APPROACH TO SUPPORT
INVESTIGATORS FROM
UNDER-REPRESENTED GROUPS.
ENHANCEMENT AWARDS FOR
UNDER-REPRESENTED MINORITY
RESEARCHERS IN HIV AIDS AND THE
ENHANCEMENT AWARDS FROM
UNDER-REPRESENTED MINORITY
SCIENTISTS.
DUE TO LEGAL DECISIONS,
REGARDING USE OF GENDER RACE
ETHNICITY IN FUNDING DECISIONS
THESE PRIOR EFFORTS WERE
DISCONTINUED.
WITHIN THE LAST YEAR HOWEVER
HERE AT THE NIH, SEVERAL OTHER
NIH INSTITUTES AND WITHIN THE OD
AND CENTERS HAVE LAUNCHED
SIMILAR PROGRAMS TO OUR PROPOSED
INITIATIVE TO ACCELERATE
ENHANCING DIVERSITY AT THE HO 1
LEVEL.
AND AFTER CAREFUL CONSIDERATION
INTERNALLY WITH OUR LEADERSHIP,
WE ARE NOW MOVING FORWARD AND
COMING TO YOU WITH THIS
DIVERSITY RO1 CONCEPT FOR
CLEARANCE.
ENHANCING DIVERSITY REMAINS ONE
OF THE NIH TOP PRIORITIES AND IT
IS A PRIORITY FOR ALL OF NIAID
SO THE OBJECTIVE OF THIS
DIVERSITY RO1 INITIATIVE IS TO
SUPPORT RESEARCH FROM NEW EARLY
STAGE AND AT RISK INVESTIGATORS
FROM UNDER-REPRESENTED
BACKGROUNDS AND BIOMEDICAL
RESEARCH TO ENHANCE DIVERSITY OF
RO1 FUNDED INVESTIGATORS.
NIAID WILL SUPPORT APPLICATIONS
RELATED TO ALL AREAS OF OUR
INSTITUTE'S MISSION WITH THE
GOAL OF DEVELOPING A DIVERSE
HIGHLY IMPACTFUL SCIENTIFIC WORK
FORCE OF THE FUTURE THAT
CONDUCTS STATE OF THE ART
RESEARCH IN INFECTIOUS
IMMUNOLOGIC ALLERGIC DISEASES.
WITH THAT, I WILL OPEN THE FLOOR
FOR DISCUSSION.
>> THANK YOU, DR. PRICE FOR YOUR
PRESENTATION.
ARE THERE QUESTIONS ABOUT THIS
INITIATIVE?
>> I HAVE ONE QUESTION.
THANK YOU SO MUCH FOR THIS
EFFORT AND LAUNCHING THIS
PROGRAM.
INTERESTED IN HOW DO YOU
DETERMINE WHAT LEVEL OF FUNDING
TO ALLOCATE FOR SUCH -- BECAUSE
CLEARLY THE NEED IS LARGE AND
COULD BE EXPANDED FURTHER.
IS THIS A PILOT PHASE?
HOW WILL THIS SORT OF THEN BE
EXPANDED IF WORKING WELL AND IF
THERE IS A BIG DEMAND?
THIS -- FOR THIS TYPE OF
SUPPORT?
>> THANK YOU FOR THAT QUESTION.
THERE'S ALWAYS COMPETING
PRIORITIES.
IN THIS FIRST PHASE, THIS FIRST
FEW YEARS, THIS WILL SET THE
STAGE AND WILL BE ABLE TO HAVE A
BETTER IDEA OF HOW MANY
APPLICANTS WE CAN EXPECT AND
FROM THERE BE ABLE TO HOPEFULLY
CROSS MY FINGERS PERSUASIVELY
ENCOURAGE ADDITIONAL RESOURCES
TO BE ALLOCATED.
AT THIS FIRST STAGE WE PROPOSED
AN INITIAL IDEA FOR WHAT WE
THOUGHT MIGHT BE A GOOD STARTING
POINT AND THEN NEGOTIATED WITHIN
OUR LEADERSHIP AND WORKING WITH
OUR OFFICE OF BUDGETS OFFICE TO
COME UP WITH WHAT WE MIGHT BE
ABLE TO DO.
SO THIS IS A PILOT PHASE AND WE
WILL SEE HOW THINGS GO AFTER
THIS AND WHAT WE ARE ABLE TO DO
IN THE FUTURE.
>> THANK YOU, LESHAWNDRA.
>> I WILL SAY THERE'S BEEN
TREMENDOUS EFFORTS AT THE T 32
LEVEL TO EXPAND DIVERSITY AND
THROUGH THE Ks SO THIS REALLY
IS A NEXT VERY IMPORTANT LOGICAL
STEP TO ENCOURAGE AND SUPPORT
THIS EFFORT.
THANK YOU.
ANY OTHER QUESTIONS?
LET ME REMIND EVERYONE TO OPEN
THEIR ELECTRONIC COUNCIL BOOKS
AND GO TO THE DAIDS TAB AND THE
DOCUMENT VOTING LINK.
THERE'S SOME NICE COMMENTS IN
THE CHAT AS WELL WHICH IN THE
INTEREST OF TIME I WON'T READ
THROUGH BUT EVERYONE SHOULD TAKE
A LOOK AT THOSE AS WE GO.
SO WHY DOESN'T EVERYONE TAKE A
MOMENT AND VOTE ON THIS
INITIATIVE.
THANK YOU AGAIN, DR. PRICE.
MENT WE APPRECIATE IT.
>> MY PLEASURE.
THANK YOU.
>> WE WILL MOVE ON TO OUR NEXT
PRESENTATION WHICH WILL BE BY
DR. GERARD LACOURCIERE, HIV
INDUCED INFLAMMATION AND IMMUNE
ACTIVATION DURING SUPPRESSIVE
DR. LACOURCIERE.
>> THANK YOU, KEN.
DO I HAVE THE NEXT SLIDE PLEASE.
THE OBJECTIVE OF THIS INITIATIVE
IS GO CUSSED ON DEFINING
MOLECULAR MECHANISMS ON HIV
PROIGNS AND NUCLEIC ACIDS
INCLUDE IMMUNE ACTIVATION DURING
VIRAL SUPPRESSION.
THE MECHANISM IS PROPOSED IN THE
RFA BY PHASIC R 33 MECHANISM, IT
IS NEW WE ARE REQUESTING A
DURATION OF FIVE YEARS.
BUDGET OF $3 MILLION, AND WE
ESTIMATE TO AWARD BETWEEN 4 TO 5
GRANTS.
NEXT SLIDE.
ANTI-RETROVIRAL THERAPEUTICS
MAKE VIRAL SUPPRESSION
ACHIEVABLE SUSTAINABLE GOAL AND
MOST PEOPLE LIVING WITH HIV
ADHERE TO THAT TREATMENT.
PEOPLE LIVING WITH HIV ARE ARE
LIVING LONGER YET THEY CONTINUE
TO EXPERIENCE ELEVATED RISK OF
CHRONIC HEALTH COMPLICATIONS
PARTICULARLY CARDIOVASCULAR
DISEASE, CANCER, COGNITIVE
IMPAIRMENT, FRAILTY.
NON-AIDS RELATED CO-MORE BITTIES
MAYBE DRIVEN AT LEAST IN PART BY
PERSISTENT LOW GRADE
IMMUNOACTIVATION AND
INFLAMMATION DESPITE SUPPRESSIVE
ART.
HIV RNA PROTEINS ARE EXPRESSED
AFTER PROLONGED ANTIVIRAL
TREATMENT.
THESE VIRAL PRODUCTS MAY
CONTRIBUTE TO INFLAMMATION
IMMUNE ACTIVATION, EXHAUSTION AS
WELL AS HIV PERSISTENCE.
HIV ANTIGEN EXPRESSION MAY DRIVE
INACTIVATION MAY LEAD TO CLONAL
EXPANSION OF RESERVOIR CELLS.
THE HIV RESERVOIR ARE VERY
HETEROGENOUS, WHILE SUPPRESS TO,
ART SOME CELLS REMAIN TOTALLY
SILENT.
THERE IS A SUBPOPULATION OF
CELLS CAPABLE OF TRANSCRIBING
VIRAL RNA, THIS ANOTHER
SUBPOPULATION CAPABLE OF TRANS
LATING VIRAL PROTEINS, AND THERE
IS ALSO ANOTHER SUBPOPULATION
THAT IS REPLICATION COMPETENT
THAT CAN REPLICATE FULLY IMPACT
VIRUSES.
SO UNDERSTANDING THE RESERVOIR
SINGLE CELL LEVEL, PROVIDE
ADDITIONAL CRITICAL INFORMATION
OF HETEROGENEITY.
THESE PROVIRUSES AND PRODUCTS
MAY BE STRONG CONTRIBUTORS TO
ONGOING ISSUE ASSOCIATED WITH
HIV INDUCED INFLAMMATION AND
IMMUNE ACTIVATION.
NIH PROVIRUS IS CAPABLE OF
TRANSCRIBING NOVEL UNSPLICED HIV
RNA AND HIV INFECTED INDIVIDUALS
ON PART.
THIS PAPER -- ON ART.
IN THIS PAPER SEVERAL DE FACTO
PRO VIRUSES WERE ISOLATED FROM
PATIENTS AND SEQUENCE ANALYSIS
REVEALED THAT THEY HAVE NOVEL
UNSPLICE HIV RNA TRANSCRIPTS AND
THEY REVEALED EXON STRUCTURE
THAT WERE DIFFERENT FROM THOSE
KNOWN FROM SLICE HIV mRNA
VARIANTS AND RANGE IN SIZE FROM
.5-KILOBASE TO 2.6-KILO BASE.
THESE TRANSCRIPTS APPROPRIATE
TRANSCRIPTION START AND STOP
SIGNALS AND THUS THEY POSSESS
TRANSLATIONALLY COMPETENT OPEN
READING FRAMES.
UNSPLICE HIV RNA TRANSCRIPTS
LACK ANY CLASSIC SPLICE SITES IN
THE GENOMES.
THIS STUDY SHOWED THAT DEFECTIVE
PRO VIRUS CAPABLE OF EXPRESSING
HIV PROTEINS THIS DEFECTIVE
VIRUS WAS FOUND TO HAVE 2.4-KILO
BASE DELETION IN DNA WHICH
AFFECTED THE HIV PROTEINS
HIGHLIGHTED IN RED.
BUT THERE ARE SOME PROTEINS SUCH
AS GAG POL AND NAF STILL PRESENT
IN FORMS AND WHAT THIS STUDY
SHOWED WAS THE NAF AND GAG
PROTEINS WERE EXPRESSED BY
DEFECTIVE PROVIRUS IN THE NORMAL
SIZE.
SO PROPOSED DE FACTO PRO VIRUSES
MAYBE BIOLOGICALLY ACTIVE AND
PLAY A ROLE IN HIV PATHOGENESIS.
THE HIV RNA TRANSCRIPTS AND
RESULTING PROTEINS EXPRESS DE
FACTO PROVIRUS MAY TRIGGER
ELEMENTS OF INNATE AND ADAPTIVE
IMMUNITY LEADING TO A STATE OF
PERSISTENT IMMUNE ACTIVATION
WITH LONG TERM CLINICAL
CONSEQUENCES.
THIS STUDY SHOWS THE HIV NEF
PROTEIN IS ASSOCIATED WITH
INFLAMMATION.
THE NEF PROTEIN IS CAPABLE OF
ENTERING BLOOD VESSELS THROUGH
THE ENDOTHELIAL CELL LINE.
ONCE ENTERS BLOOD VESSEL IT
INCREASES EXPRESSION OF
ENDOTHELIAL CELL ADHESION MARKER
SUCH AS ICAM 1 WHICH RESULTED IN
INCREASE T-CELL ADHESION TO
BLOOD VESSEL ENDOTHELIAL CELLS.
THE MORE IMPORTANTLY THE NEF
PROTEIN WAS FOUND TO ACTIVATE
THE RAP 1 PROTEIN WHICH
INCREASES REACTIVE OXYGEN
SPECIES IN THE BLOOD VESSEL.
THIS RESULTS IN APOPTOSIS OF
ENDOTHELIAL CELLS AND INCREASES
INFLAMMATION WHICH RESULTS IN
CARDIOVASCULAR DYSFUNCTION AND
INCREASES OF RISK OF
CARDIOVASCULAR DISEASE.
SO AS I MENTIONED WE ARE
PROPOSING THIS TO BE A TWO PHASE
MECHANISM R 65 PHASE IS INITIAL
PHASE, THREE YEARS IN LENGTH AND
WILL BE BASIC RESEARCH AND
SCOPE.
THE FOCUS WILL BE TO DETERMINE
THE HIV RNA PROTEIN LANDSCAPE IN
DIFFERENT CELLULAR
SUBPOPULATIONS, OFFERING INTACT
AND DEFECTIVE PROVIRUS IN
CONTEXT OF ART AND MECHANISMS
HIV RNA PROTEINS EXPRESS INTO
ART MIGHT LEAD TO INFLAMMATION
IMMUNE ACTIVATION AND IMMUNE
EXHAUSTION.
THE R 33 PHASE WILL BE TWO YEARS
IN RANGE AND WILL BE APPLIED
RESEARCH AND SCOPE.
THIS PHASE WILL BE USED TO
DEVELOP NOVEL THERAPEUTIC
STRATEGIES INTENDED TO BE USED
IN THE CONTEXT OF ART TO INHIBIT
HIV EXPRESSION FOR ALTERED
PATHWAYS HIV INEXCUSED
ACTIVATION AND IMMUNE ACTIVATION
AND IMMUNE EXHAUSTION AND
EVALUATING THESE STRATEGIES IN
SMALL ANIMAL MODELS.
INCLUDING DEVELOPMENT OF NOVEL
DRUGS THAT BLOCK HIV
TRANSCRIPTION, TAP MEDIATED
TRANSCRIPTIONAL ELONGATION
PATHWAYS THAT IDENTIFY R 61
PHASE.
ANIMAL MODEL PROOF OF CONCEPT IS
OPTIONAL GIVEN KNIFE YEAR TIME
FRAME OF THE GRANTS.
APPLICATION PROPOSED IN THE
FOLLOWING RESEARCH TOPICS WON'T
BE SUPPORTED.
IDENTIFICATION OF CELLULAR
BIOMARKERS WHICH ARE ELEVATED
DURING HIV INDUCE INFLAMMATION,
ANIMAL MODEL IS THE DIS USING
NON-HUMAN PRIMATES AND
THERAPEUTIC STRATEGIES WITH
TARGET CELLULAR BIOMARKERS.
SO WHERE DOES THIS MECHANISM
INITIATIVE FIT IN THE DAIDS
PORTFOLIO?
SONCES BIPHASIC MECHANISM FIRST
PHASE BASIC VERGE AND SECOND
PHASE IS APPLIED Z SCIENCE AT
INTERSECTION OF BASIC RESEARCH
AND TRANSLATIONAL RESEARCH, INTO
MENTION THAT THERE WAS AN RFA
APPROVED BACK IN 2012 WHICH
FOCUSED ON TARGETED INFLAMMATION
IMMUNE ACTIVATION HIV DISEASE
AND THERE WERE TWO AWARDS THAT
CAME OUT OF THIS RFA.
BOTH TARGETED CELLULAR
BIOMARKERS WHICH ARE ELEVATED
DURING HIV INDUCED INFLAMMATION
AND THERE WAS NO REAL IMPACT OF
TARGETING THESE BIOMARKERS ON
HIV INDUCE INFLAMMATION.
SO OUR ARAC MEMBERS REVIEWED
THIS PROPOSED INITIATIVE DR.
(INAUDIBLE) AND DR. JEROME AT
THE PRE-ARAC MEETING THEY BOTH
RECOMMEND THIS INITIATIVE FOR
APPROVAL.
I WILL HIGHLIGHT SOME OF THE
COMMENTS AND OUR RESPONSES.
CLARIFYING THE ANIMAL MODEL NOT
NECESSARILY REQUIRE R 33 PHASE,
SEEMS IMPORTANT.
MIGHT ALSO CONSIDER SPECIFYING
THAT SMALL ANIMAL MODELS, ARE
ANTICIPATED GIVEN BUDGET AND
TIME CONSTRAINTS.
SO WE WILL WRITE THE RFA WILL BE
WRITTEN TO CLARIFY ANIMAL MODEL
WORK IN THE R 33 PHASE.
ANIMAL STUDIES BE NOTE AS
OPTIONAL AND LIMITED USE OF
SMALL ANIMAL MODEL FOR PROOF OF
CONCEPT STUDIES.
IT MIGHT BE USEFUL TO
ACKNOWLEDGE IN THE RFA THAT THE
ISSUE OF CHRONIC INFLAMMATION
IMMUNE ACTIVATION IS ALSO LIKELY
TO BE RELEVANT IN CONTEXT OF
CURE STRATEGIES IN ADDITION TO
THE SETTING OF SUPPRESSIVE ART.
CALLING THIS OUT MAY INCREASE
INTEREST IN RESPONSE TO THE RFA.
WE AGREE WITH THAT COMMENT AND
WHEN THE RFA WILL BE WRITTEN IT
WILL INCLUDE CURE RESEARCH
STRATEGIES AS WELL.
POSSIBILITIES FOR CERTAIN NEWLY
DISCOVERED IMMUNE ACTIVATION MAY
LEAD TO NEW BIOMARKERS SOME
WHICH MIGHT BE RELEVANT
POTENTIAL THERAPEUTIC TARGETS AS
SUCH THERE MAYBE SOME AMBIGUITY
GRAY AREAS IN TERMS OF HOW
UPSTREAM AND SIGNALING THE
PATHWAYS TARGET MUST BE
CONSIDERED NEW RESPONSIVE.
RESPONSE TO ART 65 PHASE OF RFA
WILL FOCUS ON DETERMINING HIV
DERIVED PROTEINS AND NUCLEIC
ACIDS AND HOW THEY INDUCE
INFLAMMATION IMMUNE ACTIVATION.
THOUGH NEW MECHANISMS MAYBE
DISCOVERED ALONG WITH NEW
BIOMARKERS THE PROPOSED FOCUS OF
THIS RFA WILL REMAIN ON
TARGETING VIRAL COMPONENTS TO
INDUCE INFLAMMATION AND IMMUNE
ACTIVATION.
SO RFA WILL BE WRITTEN TO
EMPHASIZE THIS THERAPEUTIC
PRIORITY.
THIS IS JUST THE OVERVIEW OF THE
PROPOSED INITIATIVE, THAT
CONCLUDES MY PRESENTATION.
>> THANK YOU VERY MUCH.
QUESTIONS FOR DR. LACOURCIERE
ABOUT THIS INITIATIVE?
QUESTIONS OR COMMENTS?
IT SPEAKS TO CLARITY OF YOUR
PRESENTATION.
THANK YOU.
LET ME AGAIN ASK EVERYONE TO GO
TO THEIR ECB AND VOTE UNDER
VOTING DOCUMENTS TAB IF YOU ARE
VOTING ON THESE.
WHILE WE DO THAT WE WILL
TRANSITION TO THE NEXT
PRESENTATION WHICH WILL BE DR.
ERIC REFSLAND ON THE CENTER --
CENTERS FOR AIDS RESEARCH
DEVELOPMENTAL CENTERS, FOR AIDS
RESEARCH OR THE DC FAR.
DR. REFSLAND.
>> THANK YOU, KEN, GOOD
AFTERNOON OR GOOD MORNING,
EVERYONE.
I AM PROGRAM OFFICER PATHOYENSIS
BASIC RESEARCH BRANCH BASIC
SCIENCE PROGRAM.
I'M EXCITED TO BE PRESENTING TWO
CONCEPTS FOR REISSUE.
NIH CENTERS FOR AIDS RESEARCH
FOR CFAR AND RELATED COMPANION
CONCEPT DEVELOPMENTAL CENTER FOR
AIDS RESEARCH OR DCFAR.
PURPOSE OF CFAR PROGRAM IS
POSTER HIGH QUALITY HIV RESEARCH
BY INCREASING COLLABORATIONS IN
RESEARCH ACROSS DISCIPLINES AT
AN INSTITUTION OR BETWEEN
INSTITUTIONS.
AND ENTRANSLATION OF BASIC
RESEARCH FINDINGSINGS IN VACCINE
THERAPEUTIC HIV PREVENTION CURE
CONCEPTS MACKMIZEING EFFICIENCY
AND COST EFFECTIVENESS.
THIS IS ACCOMPLISHED WITH CENTER
CORE P 30 GRANT MECHANISM AND
TODAY I'M SEEKING APPROVAL FOR
REISSUE OF THE CFAR AND D CFAR
PROGRAMS.
EACH GRANT IS FIVE YEARS AND WE
ANTICIPATE ONE TO SIX AWARDS PER
YEAR.
THE NIAID PORTION OF THE FIRST
YEAR TOTAL COST IS 1.5 MILLION.
THE CFAR PROGRAM WAS ESTABLISHED
IN 1988 TO INCREASE
COLLABORATIVE SCIENCE AND
PROVIDE INFRASTRUCTURE SUPPORT
TO INSTITUTIONS WITH AT LEAST
$10 MILLION IN ONGOING NIH HIV
RELATED RESEARCH ACTIVITIES.
CURRENTLY WE HAVE TWO SEPARATE
FUNDING OPPORTUNITIES.
CFAR AND D CFAR, BOTH PROGRAMS
PROVIDE SHARED INFRASTRUCTURE
SUPPORT THAT IS NOT AVAILABLE
THROUGH OTHER GRANT MECHANISMS
AND BRINGS TOGETHER DISCIPLINES
GIVING INSTITUTION SCIENTIFIC
AND FISCAL FLEXIBILITY TO
RESPOND TO NEEDS OF OUR
INVESTIGATORS.
A D CFAR PROGRAM IS THOSE
INSTITUTIONS THAT HAVE THE
CRITICAL MASS OF HIV RESEARCHERS
BUT HAVE GAPS TO FILL.
DCFAR PROGRAM PROVIDES FIVE
YEARS OF FUNDING TO ADDRESS GAPS
AND STRENGTHEN PROGRAM TO BECOME
COMPETITIVE FOR A FULL CFAR.
DCFARS CANNOT BE RENEWED.
SINCE LAUNCH FOUR OUT OF FIVE
SUCCESSFULLY COMPLETED AND
TRANSITIONED TO CFAR PROGRAM.
THERE IS A FOUR TIERED STRUCTURE
SO TOTAL FUND OF THESE PROGRAMS,
D CFARS ARE CAPPED $1 MILLION
TOTAL, COST PER YEAR.
TIER 1 CFARS ARE NOSE PROGRAMS
AND INSTITUTIONS WITHIN HIV
NEXT SLIDE PLEASE.
THE C AT LEAST FAR PROGRAM IS
CO-FUNDED BY 11 INSTITUTES.
EACH INSTITUTE YEARLY
CONTRIBUTION IS LISTED IN THIS
TABLE.
THE PROGRAM IS MANAGED BY
REPRESENTATIVES FROM EACH OF
THESE INSTITUTES AND THE NIH
OFFICE OF AIDS RESEARCH AND THE
FOGARTY INTERNATIONAL CENTER.
NIAID IS THE LARGEST SINGLE
CONTRIBUTOR WITH JUST OVER $27
MILLION CONTRIBUTED YEARLY.
THE TOTAL YEARLY BUDGET FOR THE
ENTIRE PROGRAM IS $45.8 MILLION
AND THIS IS NOT INCLUDING THE
EHE APPROPRIATIONS WE WILL SAY
MORE ON IN A MOMENT.
THE CFAR PROGRAM IS HIGHLY
MULTI-DISCIPLINARY, AROUND
ONE-THIRD OF THE TOTAL NIH HIV
AIDS BUDGET IS AWARDED TO
INSTITUTIONS WITH A C FAR OR D C
FAR PROGRAM T. GRANTS MADE BY 11
CO-FUNDING NIH INSTITUTES IN
PROPORTIONS SHOWN HERE.
WITH OVER HALF COMING FROM
NIAID.
REPRESENTING THE PRIORITIES OF
EACH INSTITUTES, THESE GRANTS
AND THEIR ASSOCIATED
INVESTIGATORS RECEIVE
INFRASTRUCTURE SUPPORT AND CORE
SERVICES FROM THEIR RESPECTIVE
CFAR PROGRAMS.
THERE ARE CURRENTLY 19 FUNDED
CENTERS, 18 C FAR AND ONE D C
FAR.
HAPPY TO SUPPORT SINCE LAST
REISSUE THE PROGRAM ADDED THE
TEXAS D C FAR BAILOR COLLEGE OF
MEDICINE UNIVERSITY OF TEXAS
HEALTH SCIENCE CENTER AND TEXAS
BIOMEDICAL RESEARCH INSTITUTE IN
SAN ANTONIO.
IN ADDITION RECENTLY, UCLA AND
CHARLES UNIVERSITY OF MEDICINE
SCIENCE,INGS HAVE SUCCESSFULLY
COMPETED FOR A C FAR.
AND THE UNIVERSITY OF PITTSBURGH
JOINED WITH CASE WESTERN RESERVE
UNIVERSITY TO FORM THE RUST BELT
C FAR.
THE P 30 GRANT IS STRUCTURED OF
FOUR COURTS AND ONE SCIENTIFIC
WORKING GROUP.
THESE CORES PROVIDE SERVICES TO
INVESTIGATORS AT THEIR
INSTITUTIONS, EVERYTHING FROM
COMMUNICATION AND PLANNING
ADMINISTRATIVE CORE TO HUMAN
SUBJECT RESOURCE SUPPORT IN
CLINICAL COURSE TO DEVELOPMENTAL
CORE WHICH PROVIDES SUPPORT AND
MENTORING TO EARLY CAREER
INVESTIGATORS.
SUPPORT FOR EARLY CAREER
INVESTIGATORS CAN CORM IN THE
FORM OF FINANCIAL SUPPORT FOR
PILOT STUDIES WHICH ENABLE
INVESTIGATOR TO GATHER
PRELIMINARY DATA FOR NIH K OR R
SERIES APPLICATION.
FROM 2009 TO 2021, CFARS AWARDED
1,836 PILOT AWARDS TO EARLY
CAREER INVESTIGATORS.
DEFINED AS THOSE WHO NEVER
RECEIVED INDEPENDENT NIH AWARD.
OF THOSE NEARLY A THIRD LED TO
SUBSEQUENT GRANT, 29% RO1
EQUIVALENT, 27% K MENTORED AWARD
AND ANOTHER 20% RO 3 OR R21.
THE RETURN ON INVESTMENT IS
$6.76 FOR DOLLAR SPENT BY CFAR
ON PILOT PROJECTS THIS INCREASE
5.65 IN 2019 MEASURED FROM THE
LAST ISSUE OF CFAR PROGRAM.
ANOTHER AREA WHICH CARL AND
MAUREEN SET ME UP NICELY WERE
CFAR INVESTIGATORS PLAYED ROLES
IN ENDING THE NIH EPIDEMIC
INITIATIVE THAT AIMS TO REDUCE
HIV INFECTION BY 75% IN THE U.S.
BY 2025 AND 90% BY 2030.
48 COUNTIES SAN JUAN, PUERTO
RICO AND SEVEN STATES HIV
PRIORITY JURISDICTIONS AND ON
THIS MAP THEY ARE REPRESENTED BY
BLUE DOTS OR BLUE STATES, ALSO
SHOWN HERE ARE THE LOCATIONS OF
THE 19TH CFAR SITES RED RIBBONS
AND SEVEN NIMH AIDS RESEARCH
CENTERS, THE YELLOW STARS, THOSE
ARE THE AHRQs, BOTH
WELL-POSITIONED TO COORDINATE
RESPONSE.
EHE IS AN HHS INITIATIVE.
SHOWN HERE FUNDING TO FIVE
AGENCIES.
APPROPRIATED FUNDING BEGAN IN
2020 AND AMOUNT OF NIH RECEIVED
HAS INCREASED IN 2021 AND 2022
WITH $26 MILLION TOTAL.
ALL THE NIH FUNDING SO FAR IS
ALLOCATED TO THE NIH CFARS AND
NIMH RESEARCH CENTERS.
SO THE WORK IN EHE IS FOCUSED ON
IMPLEMENTATION SCIENCE AND
STRETCHING PARTNERSHIPS BEYOND
COORDINATING EFFORTS BETWEEN
INVESTIGATORS COMMUNITY
IMPLEMENTING PARTNERS AND LOCAL
HEALTH DEPARTMENTS BUT ALSO
HELPS SYNERGIZE OUR WORK AND
DEEPEN COLLABORATIONS.
IN PARTICULAR THE COOPERATION
COLLABORATION BETWEEN NIH AND
OTHER HHS AGENCIES ESPECIALLY
CDC AND HRSA IS CRITICAL TO
SUCCESS SO FAR.
THE NIH SPECIFIC ROLE IN THE EHE
HAS LEVERAGED FLEXIBILITY AND
ORGANIZATION AT THE CFAR AND
NIMH AHRQ, THE CENTERS FOCUS ON
O ENHANCING THE IMPLEMENTATION
KNOWLEDGE RESEARCH BASE HAIRING
BEST PRACTICES ON RESEARCH
FINDINGS AND COLLECTING
DISSEMINATING DATA ON THE
EFFECTIVENESS OF APPROACHES USED
IN THIS INITIATIVE.
NEXT SLIDE PLEASE.
SO HERE IS AGAIN SNAP SHOT OF
THE RESEARCH FUNDED BY --
THROUGH THE NIH PROJECT THE LAST
THREE YEARS OF EHE.
INCLUDED AGAIN ARE TOTAL NUMBER
OF THE PROJECTS FOR EACH YEAR
FOCUS AREA WHICH OF THE FOUR
PILLARS DIAGNOSE PREVENT TREAT
AND RESPOND OF THE EHE
INITIATIVE THE PROJECTS ADDRESS,
SHOULDN'T NOTED SOME PROJECTS
ADDRESS MORE THAN ONE PILLAR.
135 PROJECTS FUNDED TO DATE AND
THEY RANGE FROM PLANNING
PROJECTS TO FOCUS ON
DISPROPORTIONATELY AFFECTED
GROUP.
TO TEAM INITIATED PROJECTS THE
INVESTIGATOR COMMUNITY AND
IMPLEMENTING PARTNERS IDENTIFY
PROPOSE A PROJECT IN A PRIORITY
JURISDICTION AND AS CARL
MENTIONED BEFORE THE PROJECTS
FOR FISCAL YEAR 2022 CURRENTLY
UNDER CONSIDERATION.
FOR FUNDING LATER THIS SUMMER.
I WOULD LIKE TO NOW DETAIL
PROPOSED CHANGES TO CFAR AND D
CFAR PROGRAMS.
FIRST CHANGE TO TIER FUNDING
LEVELS.
THE CURRENT TIER SYSTEM I
MENTIONED BEFORE WAS FIRST
INTRODUCED IN 2003 AND IS NOT
CHANGED IN NEARLY 20 YEARS
SINCE.
THE CURRENT BASE FUNDING OF THE
CFAR PROGRAM SUPPORTS THE
EXISTING CENTERS BUT ALSO ALLOWS
FUNDING OF NEW MERITORIOUS CFAR
AND DC FARES AND ADMINISTRATIVE
SUPPLEMENTS.
WE ARE PROPOSING TO INCREASE THE
FUNDING OF EACH TIER BY $250,000
PER YEAR.
THE RATIONALE FOR THIS CHANGE IS
COUNTER INFLATION AND INCREASE
THE LOCAL CONTROL OF CFAR TO
ADDRESS SPECIFIC NEEDS.
THIS CHANGE WOULD RESULT IN
INCREASE FUNDING TO THE EXISTING
CENTERS BY TOTAL OF
$4.5 MILLION, THESE FUNDS COME
FROM OUR EXISTING BASE, NOT NEW
MONEY AND MADE POSSIBLE WITH
ADDITION OF NEW CO-FUNDING
INSTITUTES AND THE INCREASE IN
MINIMUM CO-FUNDING AMOUNT OF 1
MILLION-DOLLAR.
THIS IS A FEASIBLE CHANGE AND WE
WILL STILL RETAIN OUR
FLEXIBILITY TO FUND NEW CENTERS
AND TO MAKE SUPPLEMENTAL AWARDS
WITH ANY REMAINING FUNDS IN OUR
BASE.
NEXT SLIDE PLEASE.
THE NEXT PROPOSED CHANGE FOCUS
ON ENHANCING DIVERSITY EQUITY
INCLUSION IN THE CFAR PROGRAM,
WITH YOU HEARD ABOUT THAT TODAY
IN THE PRESENTATIONS.
THE CFARS ARE ENGAGED IN
DIVERSITY EQUITY INCLUSION
ACTIVITIES ON THE INDIVIDUAL
CFAR LEVEL AS WELL AS PROGRAM
WIDE EFFORTS TO EXAMPLES OF
WIDER EFFORTS CFARADELANTE WHICH
ENGAGES THE HISTOMA PANIC LATIN
COMMUNITIES MENTORS DECREASING
ON HIV RELATED HEALTH DISPARITY
ACE AMONG HISPANIC AND LATINX
PEOPLE.
THE GOAL OF THE CFAR PIPELINE
INITIATIVE IS INCREASE NUMBER OF
UNDER-REPRESENTED MINORS BLACK
PEOPLE INDIGENOUS, HIGH SCHOOL
GRADUATE POST GRADUATE AND
POST-DOCTORAL LEVELS AN LAUNCH
CAREERS IN SCIENCE AND MEDICINE.
THIS INCREASES COLLABORATION
WITH HBCUs AND OTHER MINORITY
SERVING INSTITUTIONS.
MORE THAN 25 SO FAR.
AND THIS IS ALSO COORDINATING
OUTREACH TO PLACES WE HAVEN'T
PREVIOUSLY ENGAGED.
SO FOR THIS ISSUE WE ISSUE I AM
PROPOSING ADDING A NEW COMPONENT
TO THE APPLICATION, DISCUSSED
PREVIOUSLY A ONE PAGE SCORABLE
PLAN FOR ENHANCING DIVERSE
PERSPECTIVES, THIS INITIALLY WAS
LAUNCHED BY THE BRAIN INITIATIVE
NATIONAL INSTITUTE NEUROLOGICAL
DISORDERS AND STROKE.
THIS COMPONENT IS NOW
REQUIREMENT IN 19 FUNDING
OPPORTUNITIES ACROSS 8 NIH
INSTITUTES, AND THE PLANS
RECOGNIZE DIVERSE TEAM WORKING
TOGETHER ON A PROBLEM
CAPITALIZING ON INNOVATIVE IDEAS
AND DISTINCT PERSPECTIVES
PERFORMS HOMOGENOUS TEAMS.
THE KEY ELEMENTS OF THE PDDP
INCLUDE RATIONALES AND TECHNICAL
MERIT OF PROGRAM THROUGH
EXPANDED ENINCLUSIVITY, THE TIME
LINE AND MILESTONES FOR THE PLAN
AND EVALUATIVE APPROACHES TO
MEASURE PROGRESS AND SUCCESS.
ADDING THIS COMPONENT TO THE D
CFAR AMPLYCATION WILL PROVIDE AM
APPLICATION WILL PROVIDE CLEAR
INSTRUCTIONS CRITERIA AND
INSTRUCTIONS FOR DEI EFFORTS
WITHIN INDIVIDUAL PROGRAM.
THE LONG TERM GOALS IN THIS
APPLICATION ELEMENT INCLUDE
INCREASE RECRUITMENT RETENTION
WITH FACULTY CFAR INSTITUTIONS
GREATER DIVERSITY IN COHORT
LEADERSHIP, MORE HIV APPLICATION
AND I WARD UNDER-REPRESENTED
INVESTIGATOR, AND EXPANSION
OFFER CREATION OF PROGRAMS
TARGETING HIV WORK FORCE
DIVERSITY.
TODAY I AM PROPOSING TWO CHANGES
TO CFAR CORES ONE CHANGE WILL
REPLACE CURRENT REQUIRED BASIC
SCIENCE WITH ADVANCED TECHNOLOGY
CORE.
THE CFAR WILL CONTINUE TO OFFER
HIGHLY UTILIZED BASIC SERVICES
BUT OFTEN SERVICES ARE HANDLED
BY INDIVIDUAL LABS OR
DEPARTMENTS.
WITH THIS CHANGE EMPHASIS WILL
BE ON INNOVATION AND ADVANCE
TECHNOLOGY SUCH AS SPECIALIZED
IMMUNOLOGY IMAGING MICROSCOPY
AND STRUCTURAL BIOLOGY.
TEN OF THE 19 CFARS HAVE THE
TYPE OF SPECIALIZED TECHNOLOGY
CORE ALREADY.
AS MENTIONED PREVIOUSLY THEY
INCREASINGLY ENGAGE IN
IMPLEMENTATION SCIENCE RESEARCH
AND CFAR INVESTIGATORS HAVE
GROWING NEED TO ACCESS EXPERTISE
AND CONSULTING SERVICES IN THIS
AREA.
WE ARE PROPOSING ADDING LANGUAGE
TO THIS REISSUE TO ENCOURAGE
APPLICANT TO ADD IMPLEMENTATION
SCIENCE CORE OR COMPONENT TO
EXISTING CORE SCIENTIFIC WORKING
GROUP.
AT THIS TIME FIVE CFARS HAVE
IMPLEMENTATION SCIENCE CORES AND
SIX HAVE EHE SCIENTIFIC WORKING
GROUPS WITH IMPLEMENTATION
SCIENCE COMPONENTS.
WE STOP SHORT OF REQUIREMENT AS
CFARS NEEDS TIME TO GATHER
EXPERTISE AT INSTITUTIONS.
WE FEEL IT IS AN IMPORTANT TO
SIGNAL INTEREST IN CFARS
PROVIDING A PLACE FOR THEIR
INVESTIGATORS CAN GET THIS KIND
OF SUPPORT FOR THEIR RESEARCH
PROJECTS.
CHANGE FOR THIS REISSUE U IN
RESPONSE TO RAPIDLY CHANGING
LANDSCAPE OF COLLABORATIVE
SCIENCE ESPECIALLY THE LAST TWO
AND A HALF YEARS.
WE ARE PROPOSING THAT
APPLICATIONS FROM GEOGRAPHICALLY
DISTANT MULTI-INSTITUTIONAL
CFARS BE CONSIDERED CFARS ARE
CENTERS AND HISTORICALLY HAVE
BEEN SUCCESSFUL IN SINGLE
INSTITUTION OR INSTITUTION IN
THE SAME CITY OR VERY CLOSE
NEIGHBOR.
RECENT WILL I THE TOOLS
COLLABORATION HAVE MADE IT
EASIER TO WORK TOGETHER AND
INTEGRATE EFFORTS AND TWO GROUPS
TEXAS D CFAR AND RUST BELT HAVE
SUCCESSFULLY COMPETED FOR
PROGRAM WITH 100 PLUS MILES
BETWEEN THEIR PARTNER
INSTITUTIONS.
THIS CHANGE CAN HELP ADDRESS THE
NEED FOR NEW CFAR PROGRAMS AND
CENTER OF THE COUNTRY AND AREAS
OF HIGH TRANSMISSION BURDEN.
I WANT TO THANK DR. AGARWAL AND
PETIFOR FOR REVIEWING THE
CONCEPTS.
EXPRESS SUPPORT FOR REISSUE OF
PROGRAMS HIGHLIGHTED A FEW OF
THEIR COMMENTS AND QUESTIONS
HERE.
ONE QUESTION WAS ABOUT COMPARING
THESE PROGRAMS TO OTHERS
REGARDING RETURN ON INVESTMENT
AND WHILE PILOT AWARDS ARE NOT
TRACKED WE BELIEVE THE CFAR ROI
IS COMPARABLE TO OTHER SIMILAR
PROGRAMS.
BOTH REVIEWERS WERE SUPPORTED OF
THE EDITION OF THE PDEP
REQUIREMENT BUT INDICATED
HELPFUL TO PROVIDE EXAMPLES TO
EMPHASIZE DIVERSITY SHOULD BE
INTERPRETED BROADLY AND WE
SHOULD STRIVE FOR FINDING THE
BALANCE BETWEEN TOO PRESCRIPTIVE
VERSUS NO SHARED UNDERSTANDING
BETWEEN APPLICANTS AND
REVIEWERS.
WE AGREE AND WE WILL PROVIDE
WHERE WE CAN WITHIN THE NIH WIDE
CONSTRAINTS ON THE USE OF PDPP
ELEMENT.
REGARDING THE CORE CHANGES ONE
QUESTION WAS WHETHER WE CONSIDER
REQUIRING THE IMPLEMENTATION
SCIENCE CORE AND AS I MENTIONED
WE PREFER AT THIS TIME TO START
WITH ENCOURAGING THIS TYPE OF
CORE RECOGNIZING THAT SOME
CENTERS ARE GOING TO NEED SOME
TIME TO DEVELOP CAPACITY TO DO
THIS.
THE FINAL COMMENT WAS GIVEN NIH
WITH NIH EMPHASIS ON BIG DATA,
DATA SCIENCE AND ARTIFICIAL
INTELLIGENCE, THE DATA SCIENCE
CORE COMPONENT COULD BE GOOD
ADDITION.
WE ENCOURAGE THESE TOPICS IN THE
PAR AS WELL.
THIS BRINGS ME BACK TO MY
SUMMARY SLIDE.
THANK YOU VERY MUCH FOR YOUR
ATTENTION TODAY AND I'M HAPPY TO
ANSWER ANY QUESTIONS YOU HAVE.
THANK YOU VERY MUCH.
WE ARE FAMILIAR WITH THE WORK IN
THE CFARS AND IMPRESSED FOR
MANY, MANY YEARS.
WE HAVE TIME FOR A FEW
QUESTIONS.
I SEE DR. WALLACE HAS A QUESTION
AND I KNOW THERE ARE AT LEAST A
COUPLE OF PEOPLE ON ARAC WHO ARE
CONFLICTED WITH THE CFARS SO I
WILL ASK YOU OF COURSE TO NOT
VOTE.
I THINK IT IS FINE FOR YOU TO BE
HERE BUT WITHOUT A VOTE ON THIS
ONE TO BE SURE.
DR. WALLACE.
>> THANK YOU.
I WON'T BE VOTING BUT WANT TO
ASK AND TO SAY THANK YOU, ERIC
FOR THIS.
I'M FAMILIAR WITH THE CFAR, WE
ARE OBVIOUSLY BEING WITH THE
CFAR BUT I'M SORT OF WONDERING
HAVE THERE BEEN ANY
CONVERSATIONS AT YOUR TEAM LEVEL
ABOUT THE CHALLENGES THAT SOME
HAVE HAD WITH MAINTAINING
COMMUNITY ENGAGEMENT MECHANISMS?
RECOGNIZING THAT SOME CFARS HAVE
HAD SIGNIFICANT CHALLENGES
MAINTAINING CABS AND WHAT
SUPPORT YOUR TEAM OR OFFICE
MIGHT BE ABLE TO PROVIDE TO THEM
REGARDING THAT.
>> THANK YOU FOR THAT QUESTION.
THAT HAS COME UP AND WE HAVE
BEEN DISCUSSING AROUND THAT
ISSUE AND HOW BEST TO WORK ON
COMMUNITY ENGAGEMENT WITHIN THE
CFAR.
THERE IS THE NCCC ORGANIZATION
THAT WORKS IN THE CFAR COMMUNITY
ENGAGEMENT.
BUT I THINK IF THERE ARE ISSUES
I THINK THAT THAT IS SOMETHING
THAT WE DEFINITELY NEED TO VISIT
AND FIGURE OUT IF THERE ARE
CFARS BEING VERY SUCCESSFUL WHAT
THEY ARE DOING AT THEIR
INSTITUTIONS TO ACCOMPLISH IT.
IT IS A VERY IMPORTANT ISSUE
BROUGHT UP AND WILL CERTAINLY
TRY TO FIGURE OUT HOW BEST TO DO
THAT.
>> OTHER QUESTIONS?
ERIC QUICK QUESTION.
IN TERMS OF EVALUATION OF THE
PEDP EFFORTS, I THINK ONE OF
YOUR SLIDES HAS A BULLET ABOUT
MEASURABLE END POINTS OR
OUTCOMES.
DO YOU HAVE A SENSE OF HOW WE
KNOW WE HAVE NOT HAD GREAT
SUCCESS AS ORGANIZATIONS OR CARL
REFERRED EARLIER I THINK ABYSMAL
WAS USED.
HOW WILL THOSE GOAL POSTS BE
ESTABLISHED FOR THESE PROGRAMS.
>> THAT IS A GREAT QUESTION.
WE ARE FORTUNATE IN THAT THESE
OTHER ICs ARE STARTING TO
ALREADY DO THIS IN THEIR
APPLICATIONS ARE BEING REVIEWED
AND APPLICANTS ARE PUTTING
TOGETHER THEIR PLANS, NONE WILL
BE EXACTLY ALIKE SO BY THE TIME
THIS IS INCORPORATED INTO THE
CFAR PROGRAM AND PAR WE WILL
HAVE QUITE A BIT OF INFORMATION
ON HOW TO DO THAT AND WE ARE IN
CLOSE CONTACT WITH THOSE
INSTITUTES THAT ARE ROLLING IT
OUT ALREADY AND I THINK THAT WE
HAVE A LOT TO LEARN ABOUT THAT.
IT IS A LEARNING PROCESS FOR
EVERYBODY INVOLVED.
BECAUSE AS CARL MENTIONED YOU
MENTIONED I THINK THERE IS A LOT
OF NEED TO IMPROVE IN THIS AREA.
THAT IS OUR APPROACH, TO JUST
LEAN HEAVILY AND REACH OUT AND
TALK TO OUR COLLEAGUES ACROSS
DIFFERENT ICs TO COME UP WITH
OUR PLAN FOR THAT.
>> THANK YOU.
OTHER COMMENTS OR QUESTIONS?
LET ME REMIND PEOPLE THERE ARE
TWO VOTES HERE.
NUMBER THREE IS FOR THE CFARS
AND NUMBER 4 IS FOR THE D CFARS
SO MAKE SURE TO MARK BOTH ON
YOUR BALLOTS PLEASE.
ALL RIGHT.
I DON'T SEE ADDITIONAL
QUESTIONS.
THANK YOU, DR. REFSLAND.
WE ARE FOR THE FIRST TIME
CERTAINLY IN MY TENURE I THINK
TEN MINUTES AHEAD OF SCHEDULE IS
THAT RIGHT?
20 MINUTES AHEAD OF SCHEDULE?
DID WE FORGET AN ENTIRE
PRESENTATION?
THAT WOULD BE MOST LIKELY FOR
ME.
BUT I DON'T BELIEVE WE DID.
SO ALL RIGHT.
WHY DON'T WE TAKE A BREAK FOR
SHOULD WE JUST TAKE TEN MINUTES?
>> TEN MINUTES.
>> WE'LL COME BACK AT 2:45.
SO REVISE YOUR SCHEDULE TO MOVE
UP 20 MINUTES EVERYONE.
THANK YOU.
WELCOME.
PEOPLE MANAGE TO STAND UP AT
LEAST IF NOT MOVE AROUND A
LITTLE BIT.
AND SO WE WILL CONTINUE.
WE HAVE GAINED 18 MINUTES ON OUR
SCHEDULE, IT LOOKS PER CHAT LIKE
ALL THE PEOPLE WHO WILL BE
PRESENTING ARE AVAILABLE.
SO IF YOU ARE ABLE TO DO THE
MATH, IT IS A LITTLE
COMPLICATED, TO MOVE AHEAD TO
STARTING WITH OUR NEXT
PRESENTATION.
WHICH WILL BE THE THERAPEUTICS
RESEARCH PROGRAM AND BOB MAHON
WILL BE PRESENTING ON ANALYZING
EARLY EVENTS IN TUBERCULOSIS AND
TB HIV INFECTION TO IDENTIFY
INTERVENTIONAL TARGETS RO1.
THANK YOU, DR. MAHON.
>> THANK YOU.
TB CLINICAL RESEARCH BRANCH
WITHIN TRP AND TODAY I WILL BE
PRESENTING OUR POTENTIAL
INITIATIVES SO THE OBJECTIVE OF
THIS INITIATIVE IS TO IDENTIFY
ESSENTIAL IMMUNOPATHOGENESIS
MECHANISMS IN EARLY NTB AND TB
HIV INFECTION TO IDENTIFY NOVEL
TARGETS FOR HOST DIRECTED
INTERVENTION.
THIS WOULD BE A NEW RO1
MECHANISM WITH ANTICIPATED
NUMBER OF APPLICATIONS BEING 8
TO 11 AND AWARD -- NUMBER OF
AWARDS BEING 3 TO 4.
WE HAVE POTENTIAL PARTNERS IN
DMID DEPENDING ON TYPE OF
APPLICATIONS WE RECEIVE.
SO AS WE ALWAYS WANT TO STATE
WHEN WE ARE TALKING TB IN HIV
AUDIENCE, PEOPLE LIVING WITH HIV
ARE INCREASE RISK OF TB DISEASE
AND RECURRENCE REINFECTION AND
TREATMENT OUTCOMES AND WE NEED
NEW THERAPEUTICS AND PREVENTIVE
STRATEGIES TO PREVENT IMPROVE
PREVENTION TREATMENT OUTCOMES,
WE NEED TO KNOW THAT THEY ARE
GOING TO BE INFECTIVE IN TB AS
WITH TB AND HIV.
WITH THIS SPECIFIC INITIATIVE
SINCE TB INFECTED INDIVIDUALS
ARE OBSERVED OR ONLY SEEN WELL
INTO THEIR INFECTION WITH
LATENCY OR LEE ACTIVATED
DISEASE, THE EARLY TB INFECTION
ARE NOT WELL THERAPY OF HTB HOST
DIRECTED THERAPEUTIC STUDY.
THE FIRST FEW WEEKS ARE CRUCIAL
DETERMINING EFFECTIVENESS OF THE
IMMUNOLOGICAL RESPONSE TO
MYCOBACTERIUM TUBERCULOSIS IN TB
AND THE CLINICAL OUTCOME,
CONTAINS CLINICALLY LATENT
DISEASE.
TWO AREAS WE SEE ARE GAP IN
OPPORTUNITIES DISTINCT MYELOID
LYMPHOID CELLS THAT PLAY CENTRAL
ROLES IN THE OUTCOME BEFORE THE
DEVELOPMENT OF ADAPTIVE IMMUNE
RESPONSES, AND THE HOW MTB IS
SUPPRESSING THE FUNCTION DURING
THIS PERIOD FOR SURVIVAL.
FURTHER ELUCIDATION OF THESE
EVANS WILL IDENTIFY TARGETS WHY
WE THINK NOW IS THE TIME FOR
THIS TYPE OF INITIATIVE.
SO SIV AND HIV INNATE IMMUNITY
INVOLVED IN MANY EARLY MTB
INFECTION WITHIN THE LUNG.
THE FIRST IMMUNE CELLS MTB COMES
IN CONTACT WITH DURING INFECTION
ARE MAY CASH FLOW PHAGOS THAT
SURVEY THE AIRWAY AND PROTECT
AGAINST FOREIGN PARTICLES
ANTIGENS AND PATHOGENS AND
REMOVE THESE ENTITIES THROUGH
PHAGOCYTOSIS WE LIMBNATING
INFLAMMATORY RESPONSE SO
PROTECTS AGAINST TISSUE DAMAGE
FOR THE LUNG AND AIRWAY.
OBVIOUSLY YOU CAN IMAGINE
PATHOGENS EXPLOIT THESE CELLS
MTB AND HIV ARE NO EXEMPTION AND
-- EXCEPTION AND FOR THEIR OWN
SURVIVAL AND HIV ANDSIVE IMPACTS
MACROPHAGE AND IN ADDITION CAN
INCREASE MTB REPLICATION.
IT DOES THIS THROUGH SEVERAL
MECHANISMS OUTLINE MISDEMEANOR
THE FIGURE INCLUDING THE
SUPPRESSION OF RECEPTORS ON THE
MACROPHAGE THAT RECOGNIZE MTB
INHADN'TING PHAGOCYTOSIS AND
PHAGOLYSOSOMAL FUSION AS WELL AS
INHEIGHTING T-CELL ACTIVATION
THROUGH SUPPRESSION OF ANTIGEN
PRESENTATION AND FACTORS ON
T-CELLS AND FURTHERMORE IMPAIRS
ANTIOXIDANT DEFENSES INCREASING
OXIDATIVE STRESS AND INHIBITS
APOPTOSIS.
IN ADDITION TO MACROPHAGES AND
HIV ALSO INHIBITS THE ANTIGEN
PRESENTING CELL FUNCTIONS OF
ANOTHER APC DENDRITIC CELLS
WHICH CAN FURTHER EXACERBATE
DELAY AND MTB INDUCED T-CELL
RESPONSES.
THIS HAS NOT BEEN WELL OR EVEN
PERFECTIVELY STUDIED IN CONTEXT
OF NATURAL HIV ESTABLISHED HIV
INFECTION IN NEW NTB INFECTION
BUT THERE ARE THEORETICAL MODELS
SUGGESTING THESE DEFECTS CAN
LEAD TO HIGHER MTB BURDENS
WITHIN FIRST FEW WEEKS OF
INFECTION BEFORE T-CELL RESPONSE
REALLY IS KICKED INTO GEAR.
THE DEPLETED T-CELLS WITHIN HIV
INDIVIDUAL INCREASES THE RISK OF
ACTIVE DISEASE.
SO WE ARE WITH THIS INITIATIVE
WE WANT TO SIMULATE AREAS THIS
AREA OF RESEARCH NEW TB
INFECTIONS IN ESTABLISHED HIV
COHORT.
OR ANIMALS.
SO THE MOST EXCITING INTERESTING
MTB RESEARCH CURRENTLY IS IN THE
WORK ON ENHANCING THE ACTIVITY
OF EFFECTIVENESS OF ONLY
APPROVED VACCINE FOR MTB KNOWN
AS MYCOBACTERIUM AS A RESULT
VIES BCG, GIVEN IN NEWBORN AND
INFANTS, PROTECTIVE AGAINST
EXTRA PULMONARY DISEASE BUT ONCE
REACHES ADOLESCENTS INTO
ADULTHOOD IT LOSES
EFFECTIVENESS.
SO THERE'S STRATEGIES, ONES THAT
RESEARCHERS ARE USING TO ENHANCE
THE ACTIVITY, I WANT TO
HIGHLIGHT ONE IN PARTICULAR
TODAY AND HOW IT TIES TO WHAT
INITIATIVE IS FOCUSED ON AND
THAT IS WHERE DR. STEVE AND
CARTER WHICH ARE TRYING TO
ADDRESS THE BOTTLENECK OBSERVED
WITH THE INABILITY TO ACTIVATE
T-CELLS IN A TIMELY FASHION BY
PULSING ECG VACCINATED MICE WITH
DENDRITIC CELLS THAT CONTAIN MTB
ANTIGEN PRIOR TO AND SOON AFTER
THE NTB CHALLENGE AND TO GET A
BETTER IMMUNE RESPONSE.
SO PREVIOUS THIS IS NEW
PUBLISHED IN 2021, PRIOR TO THIS
RESEARCH PULSE DENDRITIC CELLS
SHOW INDUCE THAT STRONGER FASTER
T-CELL RESPONSE RELATED TO
ALMOST COMPLETE CONTROL OF MTB
EARLY AFTER INFECTION IN THESE
PULSE MICE.
INCREASE WHAT THEY FOUND
SUBSEQUENTLY NOW, IS THAT THERE
IS INCREASE IN ALVEOLAR
MACROPHAGE ACCUMULATION IN EARLY
CD4 T-CELL LOCALIZATION IN THE
PARENCHYMA AIRWAYS.
FOR OUR SAKE NF KAPPA B
SIGNALING BY TYPE 2 ALVEOLAR
EPITHELIAL CELLS IS REQUIRED FOR
PULSE DENDRITIC CELL CONTROL
MTB.
MECHANISM IS NOT EXACTLY CLEAR
ONLY SHOWN IN KNOCK OUT STUDIES
SO THIS IS THE TYPE OF STUDY HOW
EXACTLY ARE INTERACTIONS WITH
DENDRITIC CELLS IN EPITHELIA
CELLS PRODUCING STRONGER T-CELL
RESPONSE OUR INITIATIVE WOULD BE
WANTING TO SUPPORT.
SO IN ADDITION TO THE WORK WITH
VACCINATIONS WE ARE ALSO
LEARNING THE PAST FEW YEARS THAT
PREVIOUSLY UNTHOUGHT OF IMMUNE
CELLS AND HAVING A ROLE IN NTB
HAVE A PROFOUND EFFECT AND
SIGNIFICANT ROLE IN CONTROLLING
TB.
SO THE TWO I WANT TO HIGHLIGHT
MOST RECENT NOTE ARE EOSINOPHILS
AND INNATE LYMPHOID CELLS SO
EOSINOPHILS FROM GROUP HERE IN
NIAID SHOWN IN ABSENCE OF
EOSINOPHILS THERE IS INCREASE
CFU COUNTS AND AS SHOWN HERE
SIGNIFICANTLY VALID COMPARED TO
WILD TYPE AND THERE INDUCTION IN
EOSINOPHIL WITNESS THE FIRST
FIVE DAYS OF THE INFECTION
COMPARED TO NEUTROPHILS WHICH
COME OUT AND IS NOT HERE IN THIS
FIGURE BUT 15 TO 20 DAYS LATER.
INNATE LYMPHOID CELLS
SPECIFICALLY ILC 3s SIMILAR
EFFECTS WHETHER INCREASE WITH TE
WHAT WE ARE ULTIMATELY WANTING
TO DO IS REFOCUS OUR ATTENTION
TO THE EARLY NTB INFECTION FROM
WHERE HOST DIRECTED THERAPEUTIC
RESEARCH IS PRIMARILY BEEN
FOCUSED ON THAT BEING THE
GRANULOMA IN ACTIVE TB.
WE THINK THAT WHILE THIS IS
IMPORTANT, THESE EARLIER EVENTS,
THERE'S ACTIVE INCREDIBLY ACTIVE
IMMUNOLOGICAL PERIOD WITH
MYELOID LYMPHOID CELLS PLAYING A
CENTRAL ROLE IN CONTROLLING THE
INFECTION WHILE NTB IS
SUPPRESSING KEY IMMUNE FOR
SURVIVAL AND THIS IS AN
UNEXPLORED AND IMPORTANT AREA OF
FOCUS WE SHOULD LOOK AT WITH HDT
RESEARCH.
SO THE SCOPE OF THIS INITIATIVE
WITH MECHANISTIC STUDIES OF NTB
OR NTB HIV OR NTB ALONE
INFECTION BEFORE FOLDED IN
ADAPTIVE IMMUNE FUNCTIONS
TYPICALLY BEFORE FOUR WEEKS.
IN THE ALVEOLAR PULMONARY TISSUE
SETTING FOCUSED ON THE
INTERACTION MYELOID LYMPHOID
CELLS WITHIN THE ALVEOLAR AND
ADJACENT LONG EFFECTS ON
DEVELOPMENT AND TIMING OF KEY
T-CELL FUNCTIONS, MTB IMMUNE
EVASION DISRUPTION OF IMMUNE
CELL FUNCTIONS, STUDIES OF HOW
HIV SIV AND SHIV MODULATE EARLY
MTB EVENTS, IMMUNITY EVENTS SO
THIS WILL BE BASIC PRE-CLINICAL
IMMUNOLOGICAL RESEARCH
IDENTIFYING VACCINE ADJUVANT IN
NEOMODULATORY THERAPEUTIC AND
VACCINE COMPONENTS FOR FURTHER
STUDY.
WHILE THIS WOULD PRIMARILY BE
STUDIES UTILIZED IN SMALL ANIMAL
MODELS AND NHPs THE USE OF
HUMAN SAMPLES WOULD BE ALLOWED.
SO OUT OF SCOPE WOULD INCLUDE
RESEARCH PRIMARILY IN LATENCY
CHRONIC DISEASE REACTIVATION
ESTABLISHED MTB INFECTION,
STUDIES FOCUS ON ONE SINGLE
IMMUNE CELL AND SPECIFIC TO
T-CELL OR JUST WANTING TO LOOK
MACROPHAGE, RESEARCH THAT ONLY
TESTS EFFECTIVENESS OF
INTERVENTION, IF YOU HAVE AN
INTERVENTION THIS NOT THE
INITIATIVE FOR YOU.
AND STUDIES FOCUSED ON
TRANSMISSION MODEL DEVELOPMENT
WOULD ALSO BE OUT OF SCOPE.
SO THERE FOR THIS DOCTORS GUPTA
AND REUBEN HARRIS, THANK THEM
FOR TIME AND EFFORT, THEY WERE
RESPONSIVE AND SUPPORTIVE AND
THOUGHT IT WAS IMPORTANT.
SOME OF THE KEY QUESTIONS AND
COMMENTS THEY HAD WAS SHOULD WE
DEFINE EARLY AS TWO TO FOUR
WEEKS, WHEN DIFFERENT ANIMAL
MODELS HAVE DIFFERENT TIME
COURSES.
WE AGREE ARBITRARY TIME FRAME
ISN'T NECESSARY, SO FOR THE RFA
WE REPHRASE TO EITHER GRANULOMA
FORMATION OR LIKELY THE FULL
DEVELOPMENT OF ADAPTIVE IMMUNE
RESPONSE.
AND WE SEE THAT AS BEING
BENEFICIAL AND MAKE THOSE
CHANGES.
THERE WAS CONCERN ABOUT
INTERACTION BETWEEN HIV AND CB
WILL BE COMPLEX TO MODEL OUTSIDE
OF HUMANS WE APPRECIATE THE
CONCERN.
AND BELIEVE THE SIV NHV MODELS
USED TO MODEL HIV TB
CO-INFECTION FOR OTHER STAGES OF
INFECTION WILL ALLOW FOR
MODELING OF EARLY EVENTS.
DOES THE STAGE OF HIV
PROGRESSION MATTER WHEN ONE
FIRST BECOMES INFECTED WITH MTB,
CONSIDERING T-CELL COUNTS?
WE BELIEVE THE STAGE OF HIV
PROGRESSION AT TIME OF MTB
INFECTION IS IMPORTANT BUT
IMPACT IS NOT -- WE HOPE TO
ADDRESS IT WITH THIS INITIATIVE.
FURTHERMORE IF PATHOLOGICAL
INTERACTIONS ARE STILL POSSIBLE
DESPITE SUPPRESSION FOR THIS
INCLUDED IN CONCEPT WE ARE
THANKFUL FOR THIS COMMENT WE
AGREE AND WE WILL INCLUDE BEING
VIRALLY SUPPRESSED DOES
SIGNIFICANTLY CONTRIBUTE TO
BETTER OUTCOMES WITH MTB BUT
DOESN'T EQUAL THOSE NEGATIVE, DO
NOT HAVE HIV SO THEY ARE STILL
PATHOLOGICAL INTERACTIONS
OCCURRING AND WE DEFINITELY
AGREE THAT THIS IS AN AREA OF
NEEDED STUDY.
SO FINAL, IT WILL BE USEFUL AND
IMPORTANT TO ASSESS AGE OF
ANIMAL SEX DIFFERENCES, WE
AGREE.
SO DOES THE NIH SEX AS
BIOLOGICAL VARIABLE IS NOW NIH
POLICY AND WE WILL ALSO MAKE A
NOTE OF AGE.
WILL BE USED IN VIVO IMAGING TO
STUDY EARLY RESPONSES IN
PRE-CLINICAL MODELS BECAUSE
EITHER ARE ALLOWED.
T IT IS ALLOWED AND NIBBING
LIKELY NECESSARY TO ACHIEVE
GOALS OF THE INITIATIVE SO
CERTAINLY BE DESIRED.
FINALLY SPECIFYING HOW THE STUDY
OF TB PREVENTATIVE THERAPY WILL
BE INCLUDED, WHETHER IT OPTIONAL
OR MUST.
THE RESEARCH DESIGN UTILIZE
METHODS OF PREVENTIVE THERAPY TO
ELUCIDATE EARLY INFECTION EVENTS
WILL BE OPTIONAL.
MOST OF THESE WILL BE VACCINE
BASED AND MAKE SURE THAT IS
CLEARING OUT AND WHEN TALKING
PREVENTIVE THERAPY WE ARE
PRIMARILY TALKING ABOUT VACCINE
RESEARCH.
FOR THAT, THAT CONCLUDES MY
PRESENTATION.
I PAM THANKFUL ONCE AGAIN FOR
THE COMMENTS AND QUESTIONS AND
LOOK FORWARD TO ADDITIONAL ONES
FROM COMMITTEE THANK YOU DR.
MAHON.
ANY QUESTIONS IN TB INFECTION
AND TB HIV INFECTION.
QUESTIONS PEOPLE MAY HAVE?
I DO NOT SEE ANY QUESTIONS.
THANK YOU AGAIN.
LET ME ASK PEOPLE TO REOPEN
THEIR ELECTRONIC COUNCIL BOOKS
IF THEY HAVE SHUT AUTOMATICALLY
WHICH THEY DO OVER TIME.
PLEASE VOTE ON THIS.
PROPOSAL.
THANKS, EVERYONE.
WE WILL MOVE TO OUR NEXT
PRESENTATION WHICH WILL BE BY
DANIELLA LIVNAT, AGAIN TB
MYCOBACTERIUM TUBERCULOSIS
QUALITY ASSESSMENT TBQA PROGRAM.
>> THANK YOU, EVERYONE FOR THE
OPPORTUNITY TO PRESENT THIS
INITIATIVE.
I'LL DANIELLA LIVNAT,
THERAPEUTIC RESEARCH PROGRAM
DIVISION OF AIDS.
N SLIDE PLEASE.
THIS OBJECTIVE OF THIS
INITIATIVE IS PROVIDE RESOURCE
TO SUPPORT ABILITY OF
LABORATORIES TO RELIABLY PERFORM
STUDY SPECIFIED MTB TESTS,
EVALUATE MTB TECHNOLOGIES AND
SPECIMEN PROCESSES FOR USING
CLINICAL INVESTIGATIONS, PERFORM
LATE STAGE VALIDATION OR AS A
TESTING OF CLINICAL SAMPLES IN A
CLEAR CERTIFIED LABORATORY.
THIS ONE IS AN OPTION.
THIS IS A CONCEPT MECHANISM
FITTED FOR RENEWAL IN FY 24,
THIS IS FOR SEVEN YEARS, WE
EXPECT ONE AWARD, AT THIS POINTE
DON'T HAVE POTENTIAL PARTNERS.
NEXT SLIDE PLEASE.
SO WHAT IS IMPORTANCE OF TBQA?
MTB CONTINUES TO BE SIGNIFICANT
PUBLIC HEALTH BURDEN AND GLOBAL
HEALTH ESPECIALLY AMONG PEOPLE
LIVING WITH HIV.
THOSE CONTINUED NEED FOR RAPID
ACCURATE AND EARLY DIAGNOSIS OF
MTB INFECTION TO FACILITATE
SCREENING AND TRIAGE, IMPROVE
CASE DETECTION, INITIATE
EFFECTIVE TREATMENT REGIMENS AND
DIAGNOSIS OF TB OF PEOPLE LIVING
WITH HIV IS MORE DIFFICULT THAN
AMONG THOSE WITHOUT HIV
INFECTION.
CONTINUED SUPPORT FROM THE TBQA
CONTRACT IS NEEDED TO ENABLE
FACILITATE ONGOING RESEARCH
EFFORTS TO DEVELOPMENT OF NEW
DRUGS VACCINES AND DIAGNOSTICS.
BY DEVELOPMENT OF NEW BIOMARKERS
AND FOR USING CLINICAL RESEARCH
AND SUPPORT OF TAB LAB RELATED
QUALITY ASSURANCE AND CLINICAL
RESEARCH.
TBQA IS A CRITICAL
INFRASTRUCTURE RESOURCE AND A
COMPONENT OF THE DAIDS TOTAL
QUALITY MANAGEMENT SYSTEM.
THE USE OF APPROPRIATE
METHODOLOGIES RELIABLE
HARMONIZED TESTING AMONG LABS
ALLOWS FOR BETWEEN STUDY
COMPARABILITY OF RESULTS AND
HENCE ABILITY TO SUSTAIN
LABORATORY END POINTS. THIS
SUPPORTS DECISION MAKING FOR
PRODUCT ADVANCEMENT AND APPROVAL
BY US AND NON-U.S. REGULATORY
ENTITIES.
SO WHAT DO WE EXPECT FROM TBQA
RESOURCE?
ACCESS TO ALLOW BSL 3 CLINICAL
LABORATORY, ACCESS TO CURRENT TB
INSTRUMENTS AND METHODOLOGIES.
ACCESS TO TB DRUGS SUCH AS
(INAUDIBLE).
DYNAMIC REPLENISHABLE REPOSITORY
OF TB ISOLATES DERIVED FROM HIV
POSITIVE NEGATIVE INDIVIDUALS,
CHARACTERIZED FOR SENSITIVITY
AND RESISTANCE TO ANTI-TB DRUGS
BY VIRUS METHODOLOGIES.
WE EXPECT ACCESS TO SPEW THEM
MATERIALS INCLUDING WHOLE BLOOD
PLASMA PBMC, SALIVA FROM
INFECTED UNINFECTED PEDIATRIC
INDIVIDUALS WITH OR WITHOUT HIV
INFECTION VACCINATED
NON-VACCINATED, AND INDIVIDUALS
NOT NTB RESPIRATORY DISEASE.
WE AIM FOR EFFICIENT
INTERACTIONS WITH INVESTIGATORS
AND PROTOCOL TOMES TO
PROACTIVELY ASSESS AND ADDRESS
LABORATORY RELATED NEEDS.
AND WE EXPECT COLLABORATION WITH
OTHER DAIDS LABORATORY CURE
RESOURCES SUCH AS THE P SMILE
CONTRACT.
SO LET'S TALK ABOUT SPECIFIC
TASKS.
SO THE KEY TASK HERE IS TO
SUPPORT ABILITY OF LABS TO
RELIABLY PERFORM STUDY SPECIFIED
NTB TEST, THIS INCLUDES EXTERNAL
QUALITY ASSURANCE EQA FOR SHORT,
THE CONTRACTOR WILL BE REQUIRED
TO ACQUIRE OR CREATE PANELS OF
SAMPLES AND PERIODICALLY SENT TO
LABS FOR TESTING.
CAPTURE RESULTS AND REVIEW
PERFORMANCE AND THEN PROVIDE
FOLLOW-UP TRAINING GUIDANCE FOR
IMPROVEMENT INCLUDING SITE
VISITS AS NEEDED.
THE FOCUS WILL BE ON CUSTOMIZE
EQA BECAUSE IF YOU STANDARDIZED
TEST LIKE AAB IS PROVIDED BY THE
P SMILE CONTRACT.
ANOTHER ELEMENT IS ACID
VALIDATION AT PARTICIPATING
LABS. THE CONTRACTOR WILL BE
EXPECTED TO PROVIDE LABS WITH
GUIDANCE AND MATERIALS SUCH AS
DRUGS, RESISTANCE STRAINS,
NON-SPEW THEM MA TRY SEIZE AND
REVIEW VALIDATION DATA.
MATRIXES.
THE CONTRACTOR WILL BE EXPECTED
TO CREATE AND DISTRIBUTE
DOCUMENTS VIDEOS, CONDUCT
WEBINARS, VISIT LABS AND TRAIN
LAB STAFF CONTRACTORS
FACILITIES.
THERE WILL BE EXPECTED TO
SUPPORT CAPACITY BUILDING OF NEW
LABORATORIES.
AND REVIEW THE IDENTIFY
LONGITUDINAL STUDY DATA PROVIDED
BY DATA CENTERS ACROSS ALL
ENROLLING SITES TO ASSESS
QUALITY INDICATORS AND INFORM
TRAINING NEEDS.
SUPPORT WILL BE EXTENDED TO
DAIDS SUPPORTED AND
COLLABORATIVE NETWORKS COHORT
AND INDIVIDUAL INVESTIGATORS.
NEXT TASK EVALUATE METHODS AND
SAMPLE PROCESSES, IT COULD BE IN
HOUSE BY CONTRACTORS LAB OR
FACILITATED BY MULTIPLE
LABORATORIES.
THE PURPOSE HERE IS TO
FACILITATE OPTIMIZATION AND
VALIDATION OF MTB ESTIMATED
METHODOLOGIES FOR IMPLEMENTATION
IN SUPPORTED OR COLLABORATIVE
STUDIES.
SO FOR MTB METHODOLOGY IT WOULD
BE EVALUATE COMPARE EXISTING OR
NEWLY DEVELOPED NTB ASSAYS, FOR
INSTANCE IF GENE SCHOLAR
(INDISCERNIBLE) ASSAY THAT
DETECTS MUTATIONS TO PREDICT
RESISTANCE TO PZA.
ASSAY KITS OR REAGENTS SUCH AS
UPGRADES TO THE GENEXPER
CARTRIDGES. ASSAYS IN
NON-SPUTUM MATRICES FUJI FILM
POC TB LAM RAPID TEST IN URINE.
SPECIMEN COLLECTION PROCESSES
SPORED SHIPPING CONDITION Z SUCH
AS THE (INDISCERNIBLE).
ANOTHER TASK IS TO VALIDATE
SCIENTIFIC DATA, WE EXPECT THE
CONTRACTOR TOO MAKE AVAILABLE A
CENTRALIZED RESOURCE TO TRIAL
GROUPS, INVESTIGATORS, AND
PUBLIC FOR RESULTS OF TBQA
EVALUATION OR COMPARATIVE
STUDIES, BEST PRACTICES,
GUIDANCE FOR PERFORMING ASSAYS
AND PROCESSING SAMPLES, GUIDANCE
AND TRAINING MATERIALS, WE USE
NEW TECHNOLOGIES AND TB RELATED
TESTING AND TREATMENT GUIDELINES
SUCH AS THOSE ISSUED BY THE
WORLD HEALTH ORGANIZATION.
PRESENTATIONS AT SCIENTIFIC
INVESTIGATOR MEETINGS AND
PUBLICATIONS IN PEER REVIEW
JOURNALS.
PERFORM LATE STAGE ASSAY
VALIDATION OR TESTING OF
CLINICAL SAMPLES IN THE COLLIEIA
CERTIFIED LABORATORY.
LET ME EXPLAIN THE OPTION IS
ADDITIONAL WORK THAT IF NEEDED,
MAY REQUIRE ADDITIONAL FUNDS.
DURING THE COURSE OF THE
CONTRACT IT MAY BECOME NECESSARY
TO USE NOVEL MTB ASSAYS IN
CLINICAL TRIALS WHERE RESULTS
WILL BE USED FOR CLINICAL
DECISIONS WITHIN THE TRIAL.
THIS WILL NECESSITATE ASSAY
VALIDATION IN A CLIA CERTIFIED
LABORATORY.
SIMILARLY IT MAY BECOME
NECESSARY OR MORE EFFICIENT FOR
THE TBQA TO PERFORM PROTOCOL
SPECIFIED MTB TESTING SUCH AS
SEQUENCING.
IF THE TESTING IS USED FOR
PARTICIPANT MANAGEMENT DECISION,
OR FOR PRIMARY IND STUDY, CLIA
CERTIFIED LABORATORY WILL BE
NEEDED.
SO A FEW WORDS ABOUT CURRENT
TBQA ACCOMPLISHMENTS.
I ORGANIZE IT ALONG SAME AREAS
OF TBQA.
SO TO SUPPORT ASSET VALIDATION
AT LABORATORIES, TBQA ALLOWED IN
GHESKIO IN HAITI TO VALIDATE TO
ASSAYS TO PARTICIPATE IN THE
ACPG TRIAL WHICH IS AN EBA
PROTOCOL.
REGARDING QUALITY CONTROL MERLES
THE ESTABLISHED REPOSITORY OF TB
ISOLATES THAT HAVE UNDERGONE
WHOLE GENOME TARGETED SEQUENCING
AS WELL AS CHARACTERIZED FOR
RESISTANCE TO CURRENTLY
AVAILABLE DRUGS BY VARIOUS
METHODS LIKE MIC MGIT HAIN
GENEXPERT AND ULTRA PLATFORM.
THEY REVIEWED DEIDENTIFIED STUDY
DATA.
THE DATA CENTER MONITORING THE
EXPERT ULTRA POSITIVE TRACE
CALLS ACROSS SITES THAT IS
POSITIVE AND REAL SOON CULTURE
POSITIVITY AND CONTAMINATION AS
WELL AS DRUG SUSCEPTIBILITY
TESTING RESULTS.
NEXT SLIDE PLEASE.
REGARDING IN HOUSE EVALUATION,
EVALUATED TRUE ARRAY NBR TB
ASSAY A PORTABLE BENCH TOP ASSAY
THAT DETECTS MYCOBACTERIAL
SUSCEPTIBILITY TO INH.
EVALUATED THE GENUS DEEPLEX NEXT
GENERATION SEQUENCING WITH
TARGETED AMPLIFICATION KIT THAT
CAN BE USED ON CLINICAL SAMPLES
AND NO NEED FOR RESULTS -- HAVE
RESULTS IN LESS THAN 48 HOURS.
EVALUATED CSF ON THE GENEXPERT
ULTRA PLATFORM INCLUDING
VARIABLES RELATEMENTED TO SAMPLE
VOLUME STORAGE CONDITIONS AND
LENGTH OF STORAGE AND THEY VALUE
WAITED METHODS TO PROCESS
GASTRIC ASPIRATES NEEDED FOR THE
PHOENIX TRIAL AND ADDRESS
VARIABLES FOR SAMPLE PROCESSING
NEUTRALIZATION AND SAMPLE
TRANSPORT.
IN ADDITION THEY PROVIDED
OVERVIEW AND TRAINING OF THE
HAIN GENOTYPE ASSAYS INTO IMPACT
ANNUAL MEETING.
NEXT SLIDE.
THIS WAS THE END OF MY
PRESENTATION.
NOT QUITE.
WE DID HAVE A PRE-ARAC REVIEW
WITH DR. ABRAMS AND GUPTA WHICH
WAS EXCELLENT.
THANK YOU VERY MUCH, BOTH
REVIEWERS BOTH SUPPORT FOR THE
RENEWAL OF TBQA CONTRACT.
ONE COMMON WAS IT WAS CRITICAL
TO EMPHASIZE THE ROLE OF TBQA
ENSURING HIGH QUALITY HARMONIZE
NTB TESTING TO SUPPORT
ASCERTAINMENT OF STUDY END
POINTS AND DEFINITELY AGREE
ANOTHER COMMENT MUST PROVIDE
CENTRALIZED RESOURCE OF GUIDANCE
MATERIALS AND BEST PRACTICES TO
STUDY TEAMS AND ALSO THE TBQA
ABILITY SHOULD BE ENHANCED AND
SO THIS IS THE END OF MY
PRESENTATION AND I WILL BE HAPPY
TO ANSWER ANY QUESTIONS YOU MAY
HAVE.
NEXT SLIDE IS REPEAT OF THE
FIRST SLIDE.
>> GREAT.
THANK YOU, THANK YOU FOR YOUR
PRESENTATION.
QUESTIONS OR COMMENTS ABOUT THE
TBQA?
LOT OF EXCITING AND OTHER
LABORATORY VALUATIONS IN TB.
I'M MOST EXCITED ABOUT FUJI LAND
POINT OF CARE.
QUESTIONS?
ALL RIGHT.
THANK YOU, DANIELLA, APPRECIATE
YOUR PRESENTATION.
WE ARE MOVING ALONG AND WE WILL
GO TO DR. QUE DANG, VACCINE
RESEARCH PROGRAM TO PRESENT
CELLULAR IMMUNOLOGY CORE
LABORATORY.
>> THANK YOU, DR. FREEBURG.
GOOD AFTERNOON, MY NAME IS QUE
TANK AND I WILL BE PRESENTING
THE CELLULAR IMMUNOLOGY CORE
LABORATORY INITIATIVE CONCEPT
FOR COUNCIL APPROVAL.
BEFORE I START TALKING ABOUT THE
CELLULAR IMMUNOLOGY CORE
LABORATORY INITIATIVE, I NEED TO
PROVIDE CONTEXT WHICH CELLULAR
IMMUNOLOGY FUNCTIONS IN THE
DIVISION OF AIDS, THE VACCINE
RESEARCH PROGRAM HAS THE ABILITY
TO EVALUATE IMMUNOGENICITY AND
EFFICACY OF CANDIDATE AIDS
VACCINES IN NON-HUMAN PRIMATES.
THIS IS POSSIBLE DURING
COORDINATED SET OF CONTRACTS
THAT CONSIST OF THE SIMIAN
VACCINE EVALUATION UNITS IN FOUR
CENTRALIZE CORE LABORATORIES.
THE SIMIAN VACCINE EVALUATION
UNITS IS A CONTRACT WE USED TO
CONDUCT THE PRE-CLINICAL
STUDIES.
THERE ARE THREE SVU SITES TO DO
THIS WORK.
THEY ARE BIOQUAL IN MARYLAND,
TULANE UNIVERSITY AND UNIVERSITY
OF LOUISIANA LAFAYETTE, BOTH IN
LOUISIANA.
TO CONDUCT THE STUDY THE SVU
SITES ACQUIRE IN AND HOUSE THE
ANIMALS DEVELOP THE PROTOCOLS,
ADMINISTER THE VACCINE AND
CHALLENGE VIRUS IF IT IS IN
EFFICACY STUDY AND COLLECT THE
SAMPLES THIS VALUABLE RESOURCE
IS AVAILABLE TO ALL AIDS VACCINE
RESEARCHERS AND CAN SUPPORT ALL
STAGES OF AIDS VACCINE RESEARCH
FROM PILOT STUDY PROOF OF
CONCEPT UP TO AND INCLUDING
EFFICACY STUDIES I WILL HAVE A
SLIDE TO GIVE YOU THE TYPES OF
IDEAS OF TYPES OF STUDIES BEING
DONE.
AND ALSO FOR THE SAKE OF TIME,
AS THIS IS NOT THE FOCUS OF
TODAY'S INITIATIVE, I INCLUDE
THE WEBSITE ADDRESS AT THE
BOTTOM OF THIS SLIDE FOR FURTHER
INFORMATION ON THE SBEU
REGARDING HOW TO ACCESS THIS
VALUABLE RESOURCE.
NEXT IN COORDINATION WITH THE
SVU, WE HAVE FOUR CENTRALIZED
CORE LABORATORIES THAT CONDUCT
STANDARDIZE ASSAYS BY SAMPLES
FROM THESE STUDIES AND CORE
LABORATORIES PROVIDE ABILITY TO
COMPREHENSIVELY EVALUATE IMMUNE
RESPONSES AND EFFICACY GENERATED
BY AIDS VACCINE CANDIDATES.
THE FOUR CORE LABORATORY ARE
NEXT.
DAVID MONTEKURY DUKE UNIVERSITY
IS PI FOR HUMORAL IMMUNOLOGY
CORE LABORATORY CONTRACT.
HUMORAL KNEWNOLOGY LAB CONDUCTS
ASSAY TO DETECT NEUTRALIZING
ANTIBODY RESPONSES THAT BREADTH
AND SPECIFICITY, MUCOSAL A IGA
AND IGG ANTIBODY AND DIFFERENT
ANTIBODY FUNCTIONS.
MICHAEL GAIL AT UNIVERSITY OF
WASHINGTON IS THE PI FOR THE
FUNCTIONAL GENOMICS CORE
LABORATORY CONTRACT.
WITH THE OVERALL GOAL OF
IDENTIFYING HOST RESPONSES THAT
PREDICT VACCINE EFFICACY THIS
APPLIES FUNCTIONAL GENOMIC
APPROACHES TO EVALUATE ADAPTIVE
IMNEIGHBOR IMMUNE RESPONSES.
TOM JENNINGS AT DUKE UNIVERSITY
IS PI FOR THE VIROLOGY MAP.
THE VIROLOGY LAB PRIMARILY
CONDUCTS ASSAYS THAT ARE USED TO
DETECT AND MEASURE LEVELS OF
VIRAL RNA TO DETERMINE WHETHER
LASTLY WE HAVE THE CELLULAR
IMMUNOLOGY LAB, THE FOCUS OF
TODAY'S INITIATIVE.
THE PI FOR THE CELLULAR
IMMUNOLOGY LAB IS (INAUDIBLE) AT
THE PRIMATE CENTER AT TULANE
UNIVERSITY.
TOGETHER THESE FOUR CORE
LABORATORIES ARE RESPONSIBLE FOR
STATE OF ART ASSAYS TO EVALUATE
IMMUNOGENICITY AND/OR EFFICACY
OF CANDIDATE AIDS VACCINES.
I HOPE THIS HELPS YOU TO BETTER
UNDERSTAND THE CONTEXT IN WHICH
THE CELLULAR IMMUNOLOGY LIBRATES
AND E WILL NOW PRESENT THE
INITIATIVE CONCEPT.
THE OBJECTIVE IS TO HAVE A
CELLULAR IMMUNOLOGY LABORATORY
TO PROVIDE A CENTRALIZED SERVICE
TO CONDUCT ASSAYS MEASURING
CELLULAR IMMUNE RESPONSES IN
SUPPORT OF PRE-CLINICAL AIDS
VACCINE STUDIES.
THIS ENSURES STANDARDSIZATION
AND COMPARABILITY OF DATA ACROSS
STUDIES.
THE ASSAYS ARE ESSENTIAL FOR THE
EVALUATION OF THE IMMUNE
GENICITY OF CANDIDATE AIDS
VACCINES FOR POTENTIAL
IDENTIFICATION OF PROTECTIVE
IMMUNE RESPONSES IN EFFICACY
STUDIES.
IF APPROVED, THIS WILL BE A
REISSUE OF THE CURRENT CONTRACT
USING REQUEST FOR PROPOSAL FOR
RFP SOLICITATION.
THE CONTRACT WILL BE AWARDED FOR
SEVEN YEARS AND WE ANTICIPATE
MAKING ONE AWARD.
SO WHY IS THIS INITIATIVE
IMPORTANT?
WHY DO WE NEED TO DO THIS NOW?
THE DEVELOPMENT OF EFFECTIVE HIV
VACCINE IS A HIGH PRIORITY FOR
THE NIH.
PRE-CLINICAL STUDIES NON-HUMAN
PRIMATES ARE SMALL ANIMALS KEY
TO EVALUATE THE IMMUNOGENICITY,
EFFICACY AND TOXICITY OF THAT
VACCINE CANDIDATE, PRE-CLINICAL
STUDIES ARE IMPORTANT TO DERISK
THE PRODUCT IN PLATFORM IN
COSTLY GMP MANUFACTURING AND
THEY CAN HELP TO INFORM GUIDE
PHASE 1 CLINICAL TRIALS STUDIES.
THE CELLULAR IMMUNOLOGY
LABORATORY AND ALL THE LAB
CATEGORIES ARE CRITICAL FOR
EVALUATION OF THESE POTENTIAL
VACCINES SO THIS TABLE SHOWS YOU
THE SBU STUDIES THE CELLULAR
IMMUNOLOGY LAB SUPPORTED OVER
THE LAST FEW YEARS.
THEY WERE SELECTED TO EXPLORE
VARIOUS QUESTIONS.
FOR EXAMPLE IN P 209 DR. CROTTY
ASKED WHETHER SLOW DELIVERY
IMMUNIZATION ENHANCE
NEUTRALIZING ANTIBODY IN
GERMINAL CENTER REACTIONS OVER
CONVENTIONAL STRATEGIES AND THE
ANSWER WAS YES.
IN P 213 WE REPEAT TO CONFIRM
PRE-CLINICAL STUDY BY DR.
HUNTERS AND AMARA VACCINE INDUCE
CELLULAR IMMUNE RESPONSE REDUCE
THRESHOLD OF NEUTRALIZING
ANTIBODIES REQUIRED TO CONFER
SUPERIOR AND DURABLE PROTECTION.
I WOULD LIKE TO ALSO POINT OUT
AS MENTIONED ON THE PREVIOUS
SLIDE THESE PRE-CLINICAL STUDIES
MAY ALSO HELP TO GUIDE INFORM
PHASE 1 TRIALS.
SUCH AS WAS THE CASE WITH P 192
WITH DR. ROBINSON WHERE PRODUCTS
PLATFORM WENT ON TO BE TESTED IN
THREE CLINICAL TRIALS.
HBTN 094, 114 AND 205.
NEXT.
IN P 210A THIS PRE-CLINICAL
STUDY IS CONDUCTED IN PARALLEL
WITH THE CLINICAL TRIAL HBTN 137
TO COMPARE THE IMMUNOGENICITY OF
DIFFERENT ADJUVANTS.
THUS IN ITS CAPACITY THE
CELLULAR IMMUNOLOGY LAB SUPPORTS
AND CONTRIBUTES TO THE
EVALUATION OF ALL THESE VACCINE
CANDIDATES.
THE CURRENT ACTIVITIES OF THE
CELLULAR LAB ARE TO DEVELOP
OPTIMIZE AND VALIDATE CELLULAR
ASSAYS.
EXAMPLES OF SUCH ASSAYS ARE THE
ELISPOT FLOW BASE ASSAY Z SUCH
AS INTRACELLULAR CYTOKINE
STAINING ACTIVATION IMMUNE
MARKER OR ASSAYS AND CELL
SORTING.
IN ADDITION THE LAB GENERATES
STANDARDIZED SOPs FOR
EQUIPMENT OPERATION AND VARIOUS
PROCESSES SUCH AS ANTIBODY
TITRATION AND HOW TO PROCESS
MUCOSAL SAMPLES.
IMPORTANTLY, ALL THE WORK DONE
BY THE LABORATORY FOLLOWS GOOD
LABORATORY PRACTICE OR GLP.
THE CELLULAR LAB IS ABLE TO
CONDUCT ASSAYS ON FRESH AND
FROZEN PBMCs WHOLE BLOOD
MUCOSAL TISSUE AS WELL AS
LYMPHOID TISSUES.
AND THE DATA GENERATED FROM
THESE ASSAYS ARE ANALYZED USING
DIFFERENT ANALYTICAL SOFTWARE
SUCH AS FLOW JOE, PRISM, UMAP
AND R AND PUBLICATION QUALITY
FIGURES CAN BE GENERATED.
LASTLY FROM START TO FINISH, ALL
THESE ACTIVITIES ARE REVIEWED BY
INDEPENDENT QUALITY ASSURANCE
UNIT.
THE CURRENT CONTRACT IS ABOUT 28
VALIDATED ASSAY SOPs.
FOR THE SAKE OF TIME, I WON'T GO
THROUGH THE LIST BUT I WILL
BRIEFLY GO OVER AWE THE ASSAYS
ARE VALIDATED LATER IN THE
PRESENTATION.
IN ADDITION TO THE ASSAYS, THE
CURRENT CONTRACT HAS DEVELOPED
20 VALIDATED EQUIPMENT SOPs.
I THINK IT IS EASY TO UNDERSTAND
WHY THE ASSAYS ARE VALIDATED.
BUT YOU MAY WONDER WHY IT IS
IMPORTANT TO HAVE A VALIDATED
PROTOCOL FOR EQUIPMENT SUCH AS
FREEZERS AS AN EXAMPLE.
SO AS YOU CAN IMAGINE WE DO NOT
WANT TO RISK LOSING THOUSANDS OF
SAMPLES SO WE HAVE AN AUTOMATED
MONITORING SYSTEM AS WELL AS
MANUAL CHECKS TO ENSURE THE
PROPER TEMPERATURE AND STORES OF
THE SAMPLES.
AND BECAUSE CELLULAR IMMUNOLOGY
LAB WORKS UNDER GLP LIKE
PRACTICES THESE SOPs ARE
IMPORTANT FOR DOCUMENTATION
WHICH ARE REVIEWED BY THE
INDEPENDENT QUALITY ASSURANCE
PROGRAM.
TO GIVE YOU A SENSE OF WHAT WE
ARE ABLE TO DO THE LAB HAS THE
CAPABILITY TO CONDUCT COMPLEX
SORTING TO ISOLATE RARE ANTIGEN
SPECIFIC B CELLS FROM LYMPH
NODES.
THIS IS QUITE LABORIOUS AND
THESE SORTS CAN TAKE THE WHOLE
DATA RUN.
IN CONTRAST TO THIS TYPE OF CELL
SORT THE LAB CAN CONDUCT HIGH
THROUGH PUT SORTING WITH UP TO
18 HIGH PURITY SORTS.
AS AN EXAMPLE WE CAN CONINE
ANIMALS WITH TWO SAMPLES A DAY.
IN EITHER CASE THE SORTED CELLS
ARE USED FOR OTHER COULDN'T
STREAM APPLICATIONS SUCH AS 10X
GENOMICS OR CELL SPECIFIC RNA
SEQ.
NEXT.
THE LAB ALSO HAS THE CAPABILITY
TO CONDUCT FLOW BASE ASSAYS,
THEY CAN DESIGN AND OPTIMIZE UP
TO 20 PARAMETER PANELS.
THEY CAN ALSO CONDUCT ABSOLUTE
COUNTS, HAVE HIGH THROUGH PUT
ACQUISITION AND HAVE EXPERTISE
IN CELL PROLIFERATION AND CELL
OF CYCLE ASSAYS SUCH AS THE BRDU
AND CFSE ASSAYS.
LASTLY THEY ALSO HAVE THE
EXPERTISE TO CONDUCT ASSAYS TO
EXAMINE PHAGOCYTOSIS.
AN EXAMPLE OF HIGH THROUGH PUT
ACQUISITION SINCE THE START OF
THE CONTRACT THEY HAVE RUN
20,000 FAX TUBES FOR FLOW SIGH
FOE ME TRUCK ASSAYS ALONE.
THE CONDUCT OF ASSAYS IS
OBVIOUSLY INTEGRAL TO CONTRACT
ACTIVITIES.
HOWEVER, THE DATA ANALYSIS IS
NOT USUALLY EMPHASIZED AS MUCH.
HERE IN THE NEXT FEW SLIDES I
WANT TO DEMONSTRATE THAT NOT
ONLY DATA -- NOT ONLY ARE THE
DATA ANALYSES EQUALLY AS
IMPORTANT AS ASSAYS THEMSELVES.
BUT THE CURRENT CONTRACT ALSO
UTILIZES STATES OF THE ART
METHODS FOR DATA ANALYSIS.
AS JUST MENTIONED, THE CELLULAR
IMMUNOLOGY LAB IS ABLE TO DESIGN
A FLOW PANEL UP TO 28 PARAMETERS
OR CELL MARKERS TO PHENOTYPE
IMMUNE CELL POPULATIONS.
THE DATA OBTAINED ARE THEN
COMMONLY VISUALIZED USING
SCATTER PLOTS.
YOU CAN DRAW GATES AROUND THE
POPULATION OF INTEREST TO
FURTHER DRILL DOWN TO SPECIFIC
MARKER YOU ARE ANALYZING.
DRAW BACK IS THIS IS ONLY DONE
WITH TWO PARAMETERS OR MARKER AT
A TIME.
ONE MARKER ON THE Y AXIS AND ONE
ON X AXIS.
YOU HAVE 28 MARKERS NEED TO BE
ANALYZED IN DIFFERENT
COMBINATIONS.
AS YOU CAN IMAGINE YOU CAN END
UP WITH LOTS OF LITTLE GRAPHS
THAT LOOK LIKE THIS.
YOU HAVE HUNDREDS OF LOW GRAPHS
BUT WHAT IF YOU HAVE MULTIPLE
TISSUES TO ANALYZE?
HERE WE HAVE DATA ON CELLS TAKEN
FROM THE BLOOD PBMCs AND ALSO
CELLS FROM THE COLON.
SO NOT ONLY DO YOU HAVE TO
ANALYZE DATA FROM THE SAME
ANIMAL, WITH DIFFERENT TISSUES
NOW YOU HAVE MULTIPLE TIME
POINTS. YOU DON'T DO A STUDY
WITH ONE ANIMAL, U YOU DO THE
SAME ANALYSIS FOR MULTIPLE
ANIMALS.
SOME OF THESE SBU STUDIES CAN
HAVE UP TO 20 TO 30 ANIMALS.
DEPENDING ON THE STUDY, WE HAVE
DIFFERENT -- SEVERAL DIFFERENT
PHENOTYPE PANELS TO ANALYZE.
SO EACH PRE-CLINICAL STUDY CAN
GENERATE HUNDREDS AND HUNDREDS
OF THESE LITTLE GRAPHS.
WHILE THERE IS NOTHING WRONG
WITH THIS ANALYSIS AND DOES HAVE
ITS PLACE, TO TRY TO GET A
GLOBAL PERSPECTIVE OF WHAT IS
HAPPENING AFTER VACCINATION
AND/OR INFECTION IS VERY
DIFFICULT.
A DIFFERENT METHOD OF ANALYSIS
MUST BE DONE IF YOU WANT TO GET
A GLOBAL SENSE OF THE IMMUNE
RESPONSE.
IN THE PREVIOUS SLIDES WE ARE
ONLY ANALYZING TWO VARIABLES AT
A TIME.
BUT IF YOU WANT TO LOOK AT ALL
28 VARIABLES YOU NEED WAY TO
PERFORM A MULTI-DIMENSIONALITY
ANALYSIS AND GRAPH IT ON A 2D
PLOT TO VISUALIZE THE DATA.
ONE METHOD IS THE PRINCIPLE
COMPONENT ANALYSIS.
WHICH YOU MAY BE LIKELY FAMILIAR
WITH OR AT LEAST HEARD OF.
PCA IS A LINEAR PAIR WISE TYPE
ANALYSIS BUT IN THE RESULTING
DATA, IT IS HARD TO TEASE OUT
THE INDIVIDUAL POPULATION.
THEN IN 2008 THE STOCHASTIC
NEIGHBORHOOD EMBEDDING ANALYSIS
WAS DEVELOPED.
THIS METHOD UTILIZES A
NON-LINEAR DIMENSIONALITY
REDUCTION ALGORITHM.
YOU BEGIN TO SEE INDIVIDUAL
POPULATIONS BUT THEY STILL ARE
NOT SEPARATED WELL.
THE UNIFORMMAN FOLD
APPROXIMATION AND PROJECTION
AREN'T YOU GLAD OF THESE
ACRONYM?
NON-LINEAR DIMENSIONALITY
REDUCTION ALGORITHM WHEN THAT
WAS RECENTLY DEVELOPED IN 2018.
THIS METHOD PRESERVES LOCAL
GLOBAL STRUCTURE INCLUDING
CLUSTER DISTANCE AND WHAT THAT
BOILS DOWN TO IS THAT YOU NOW
GET MORE DEFINED AND SEPARATED
CELL POPULATION.
SO SURE THAT WAS A BIT MIND
NUMBING BUT WHAT DOES THIS DATA
REALLY LOOK LIKE ONCE EMPLOY
THESE DIMENSIONALITY REDUCTION
METHODS?
SO AS A REMINDER THIS IS WHAT WE
STARTED WITH.
HUNDREDS OF THESE LITTLE GRAPHS.
WE WANT TO RECUSE NUMBER OF
GRAPHS TO LOOK -- REDUCE NUMBER
OF GRAPHS TO LOOK AT VARIABLES
AT ONCE.
SO USING THE TISNE METHOD YOU
CAN TRANSFORM THE DATA TO GET
ONE GLOBAL PICTURE.
FROM THIS GLOBAL PICTURE YOU CAN
THEN DRILL DOWN IDENTIFY AND
CHARACTERIZE CELL POPULATION OF
INTEREST BASED ON GROUPS FORMED
AS DEPICTED BY THE REGION
OUTLINED IN BLUE.
EARLIER I SAID WE CAN ALSO
CONDUCT ASSAYS ON MULTIPLE
TISSUES.
HERE HAVING THE ABILITY TO
QUICKLY COMPARE BETWEEN TWO
TISSUES IS HELPFUL.
AND IN THIS CASE THE DECIDUA, A
SPECIALIZED LAYER OF THE
ENDOMETRIUM IN UTERUS THAT FORMS
IN PREGNANCY IS IS IN THE TOP
MIDDLE PANEL AND PBMCs ARE
BOTTOM MIDDLE PANEL.
WITH JUST A GLANCE ONE CAN
READILY SEE GLOBAL DIFFERENCES
BETWEEN THE TWO SAMPLES WITHOUT
HAVING TO LOOK AT A BUNCH OF
LITTLE GRAPHS.
FINALLY, WE GET TO WHAT THE DATA
WOULD LOOK LIKE WHEN YOU
TRANSITION FROM TSNE TO U MAP
ANALYSIS.
HERE YOU CAN CLEARLY SEE THAT
THE DIFFERENT CELL POPULATIONS
ARE NOW WELL DEFINED AND
SEPARATED.
SO THE OVERALL POINT I'M TRYING
TO MAKE, OVER THE LIFE SPAN OF
THE CONTRACT, AS THE FIELD
CHANGES, NOT ONLY DO TYPES OF
ASSAYS NEED TO ADAPT AND EVOLVE
JUST AS IMPORTANTLY, SO DO THE
METHODS FOR DATA ANALYSES.
MAINTAINING STATE OF THE ART
CAPABILITIES IS REQUIREMENT
WRITTEN INTO THE STATEMENT OF
WORK IN THE CONTRACT.
CONDUCTED BY CELLULAR IMMUNOLOGY
LABORATORY ALLOW COMPARISON
ACROSS MULTIPLE STUDY.
WE HAVE PROCEDURES IN PLACE WITH
INTERNALLY AND EXTERNALLY TO
ENSURE RIGOR AND REPRODUCIBLE.
INTERNAL MEASURES INCLUDE USE OF
REFERENCE CONTROLS SASS INTERNAL
QC QUALITY CONTROL AND ASSAYS,
AND WHEN NEW ASSAYS ARE
VALIDATED WE HAVE A LARGE
REFERENCE PANEL USED AS
REFERENCE CONTROL SAMPLES.
WE VALIDATE ASSAYS USING THE
RULE 3 SUCH AS TESTING TWO OR
THREE OPERATORS, THAT DEPENDS ON
NUMBER OF PERSONNEL STAFF WE
HAVE.
EACH CONDITION TESTED IS DONE
TRIPLICAT AND TESTING IS DONE ON
THREE DIFFERENT DAYS.
THIS ALLOWS US US TO EVALUATE
THE INTRAAND INTERASSAY AND THE
ENTER AND INTEROPERATOR
VARIABILITY MEASURED USING THE
MIEN STANDARD DEVIATION AND
COEFFICIENT OF VARIATION AS
PARAMETERS.
LASTLY, CROSS TRAINING OF STAFF
ASSAYS ARE DONE TO ENSURE
SEAMLESS COVERAGE AND THIS
ALLOWS US TO MINIMIZE
INTEROPERATOR VARIABILITY.
OUR EXTERNAL PROCEDURES TO
ENSURE RIGOR AND REPRODUCIBILITY
INCLUDE REGULAR INSPECTIONS BY
INDEPENDENT QUALITY ASSURANCE
UNIT OF ALL SOPs, ALL
DOCUMENTATIONS, EQUIPMENT AND
TRAINING.
IN ADDITION, THIS UNIT ATTENDS
ALL BIWEEKLY CALLS.
THE LABORATORY ALSO PARTICIPATE
IN THE EXTERNAL QUALITY
ASSURANCE PROGRAM OR EQUIPAL.
ELISPOT AND FLOW CYTOMETRY
ASSAYS ACT CANNED THROUGH EQAPOL
AND THIS IS DONE ANNUALLY.
YOU WILL HERE MORE ABOUT THE
EQAPOL BY MY COLLEAGUE MILTON
MACIEL RIGHT AFTER THIS
PRESENTATION.
SO FOR THE REISSUANCE OF THIS
CONTRACT THE CONTRACT WILL BE
EXPECTED TO MAINTAIN STATE OF
THE ART CAPABILITY FOR THE
CONDUCT OF CELLULAR IMMUNE SAYS
IN SUPPORT OF PRE-CLINICAL SAW
STUDIES.
ADDITIONALLY WE PROPOSE TO
EXPAND ACTIVITIES TO CONDUCT
ASSAYS ON SMALL ANIMALS.
NOT EVERY PRE-CLINICAL STUDY
NEEDS TO BE DONE ON NON-HUMAN
PRIMATES.
AND WITH THE LIMITED NUMBER OF
NHPs AVAILABLE, EXPERIMENTS
USING DIFFERENT MOUSE MODELS
MAYBE APPROPRIATE AND WE WOULD
LIKE TO BE ABLE TO SUPPORT THESE
STUDIES.
WE WOULD ALSO LIKE TO BROADEN
THE SCOPE OF THE CONTRACT FROM
JUST HIV TO OTHER PATHOGENS.
IN PARTICULAR WE WERE THINKING
ABOUT BEING ABLE TO SUPPORT TB
VACCINE STUDIES IN THE CONTEXT
OF MYCOBACTERIUM TUBERCULOSIS
AND SIV HIV CO-INFECTION.
MOREOVER THE BROADER SCOPE WOULD
ALLOW US TO HAVE GREATER
FLEXIBILITY AS PART OF THE
EFFORTS FOR PANDEMIC
PREPAREDNESS SHOULD THE NEED
ARISE.
LASTLY, WE WILL REQUIRE THAT ALL
DATA BE DEPOSITED INTO A MORE
CENTRALIZED DATABASE.
THE REVIEWERS FOR THIS
INITIATIVE WERE DR.S FREEBURG
AND JEROME, THEY WERE SUPPORTIVE
OF THE CONCEPT.
THEY WROTE I'M ENTHUSIASTIC
ABOUT THE CELLULAR IMMUNOLOGY
CORE LAB.
AND THIS IS AN IMPORTANT RFA.
THERE IS A CLEAR NEED FOR WELL
STANDARDIZED ASSAYS ESPECIALLY
IN THE PRE-CLINICAL AND CLINICAL
STUDY SPACE.
WITH THAT WELL STANDARDIZED
ASSAYS WORK IS NOT EASILY
COMPARED BETWEEN STUDIES
HAMPERING PRIORITIZATION OF
VACCINES AND SLOWING THE ENTIRE
ENTERPRISE.
SO THANK YOU, VERY MUCH, DR.
FREEBURG AND JEROME.
DR. FREEDBERG HAD COMMENTS
REGARDING THE PRESENTATION.
ONE TO CLARIFY THE RELATIONSHIP
AND STRUCTURE BETWEEN THE SVU
SITES, AND THE DIFFERENT CORE
LABS ALONG WITH AN EXPLANATION
OF HOW PROJECTS ARE CHOSEN FOR
SUPPORT.
HIGHLIGHTING THE RANGE OF ASSAY
SOPs AND EQUIPMENT SOPs IS
KEY TO UNDERSTANDING THE LAB
VALUE.
THREE, EXPANDING THE DESCRIPTION
OF THE U MAP APPROACH BRIEFLY,
WOULD BE HELPFUL FOR THE
NON-BASIC SCIENTIST ON ARAC AND
AT THE MEETING.
SOME LISTENERS MAYBE MORE
FAMILIAR WITH PRINCIPLE
COMPONENT ANALYSIS AS A STARTING
POINT FOR EXPLAINING THE CUTTING
EDGE WORK THIS GROUP HAS DONE
TRANSITIONING FROM TSNE TO MAP
UMAP.
KNEW THANK YOU FOR YOUR
SUGGESTIONS TO MAKE THE
PRESENTATION CLEAR.
YOUR COMMENTS HAVE BEEN
INCORPORATED TO THIS REVISED
PRESENTATION.
LASTLY, THEY SAID CLOSE
COORDINATION WITH THE ANALOGOUS
HUMAN CORE LAB IS IMPORTANT.
THERE ARE PEERS WHO CAN BENEFIT
FROM ADVANCES IN EACH AND
COORDINATION BETWEEN THE TWO IS
TRANSITION TO CLINICAL TRIALS.
YOU MIGHT CONSIDER CALLING OUT
THE DESIRE FOR SUCH CONTACT
CLEARLY IN THE RFA.
THANK YOU.
WE AGREE WHERE APPLICABLE HAIR
MNIZATION OF PROTOCOLS WITH OUR
CLINICAL PEERS IS IMPORTANT AND
WE WILL ENCOURAGE AND FACILITATE
SUCH INTERACTIONS.
IN CONCLUSION WHICH ARE ASKING
FOR APPROVAL TO REISSUE A
CONTRACT THAT WILL PROVIDE A
CENTRALIZED SERVICE TO CONDUCT
MEASURE CELLULAR IMMUNE RESPONSE
IN SUPPORT OF PRE-CLINICAL
STUDIES.
THANK YOU FOR YOUR ATTENTION.
I WOULD BE HAPPY TO ANSWER ANY
QUESTIONS.
>> THANK YOU, DR. DANG,
APPRECIATE YOUR PRESENTATION.
QUESTIONS FROM THE COMMITTEE?
OR OTHERS?
>> THANK YOU -- CAN YOU HEAR ME?
>> GO AHEAD PAUL.
>> APPRECIATE THE PRESENTATION
I'M FULLY SUPPORTIVE.
I WANT TO KNOW, I THINK IT WAS
MENTIONED BY THE REVIEWERS SO
HOW ARE PROTOCOLS CHOSEN AND DO
THEY -- HOW IS EVERYTHING
COORDINATED?
SEEMS LIKE THERE IS A LARGE PART
LARGE COORDINATION EFFORT THAT
IS DONE.
FINALLY, ARE THERE AREAS WHERE
THINGS CAN BE SHARED SUCH AS
BIOINFORMATICS THAT YOU WERE
DESCRIBING?
EACH HAS ITS OWN SPECIFICS BUT
CAN THAT BE SHARED?
>> YES.
THE STUDIES ARE CHOSEN ON
PROGRAMMATIC PRIORITY.
WE ARE LOOKING TO ANSWER
SPECIFIC QUESTIONS.
SOMETIMES IT IS A PLATFORM
QUESTION, SOME OF THE EXAMPLES I
GAVE ONE WAS TO SEE IF SLOW
DELIVERY OF WILL BE SUPERIOR TO
WHAT IS CONVENTIONALLY GIVEN
WHICH IS A LARGE WHOLE LIST OF
THE IMMUNOGEN AND AS AN EXAMPLE
OF THE OTHER STUDY WE ARE DOING
CURRENTLY WHICH WAS P 213 IS TO
CONFIRM REPEAT AND CONFIRM WHAT
THEY OBSERVED IN THEIR STUDY
WHICH WAS THAT CELLULAR IMMUNE
RESPONSES WERE ABLE TO LOWER THE
THRESHOLD OF NEUTRALIZING
ANTIBODIES SHOWN TO BE
PROTECTIVE IN THEIR STUDY.
SO THAT IS HOW STUDIES ARE
CHOSEN.
THE BIOINFORMATICS, THE ANSWER
TO YOUR QUESTION IS COMPLICATED
BECAUSE SOME OF THESE PLATFORMS
ARE PROPRIETARY.
WE HAVE INDUSTRY THAT WE
SOMETIMES SUPPORT STUDIES FOR
WHERE WE HAVE INVESTIGATORS WHO
ARE NOT QUITE YET READY TO
ADVANCE PRODUCT AND EXPLORATORY.
SO WHERE AND WHEN POSSIBLE WE
CERTAINLY TO MAKE AVAILABLE THE
INFORMATION.
THAT IS WHAT IN PART WE WANT TO
HAVE A CENTRALIZED DATABASE SO
THAT WHEN THE DATA IS ABLE TO BE
SHARED THEN WE CAN INVITE THE
FIELD TO LOOK AT THE DATA MORE
CLOSELY.
THANK YOU FOR YOUR QUESTION.
>> WE HAVE A QUESTION FROM DR.
GANDHI.
>> THANK YOU SO MUCH, REALLY
IMPORTANT CELLULAR IMMUNITY IS
SO IMPORTANT FOR ALL SORTS OF
INFECTIONS.
I GUESS THE QUESTION IS, IS THIS
A RESOURCE AND THEN PEOPLE WOULD
APPLY TO HEY IN THIS INFECTION,
DUETTING MORE FUNDING WE NEED TO
LOOK MORE DEEPLY DIFFERENT
IMMUNE RESPONSE?
WOULDN'T BE FOR SPECIFIC
INFECTIONS.
IT WOULD BE JUST WHATEVER WAS
HAPPENING AT THE TIME.
THAT IS WHAT -- I GUESS THAT'S
WHAT I'M TRYING TO UNDERSTAND
BECOME A CORE RESOURCE LAB
MULTIPLE GRANTS TO FEEDS INTO.
TO USE THIS LAB THIS RESOURCE TO
ENHANCE EVALUATION IMMUNITY TO
INFECTIOUS DISEASES.
>> THANK YOU FOR THAT GREAT
QUESTION.
THE CONTRACT IS CURRENTLY SET UP
TO SUPPORT PRIMARILY OUR
PRE-CLINICAL STUDIES CONDUCTED
THROUGH THE SBU.
UNFORTUNATELY OUR BUDGET AT THIS
TIME IS NOT ENOUGH TO SUPPORT
OTHER INVESTIGATORS ON THEIR
GRANTS BUT OCCASIONALLY WE NOT
SO MUCH FOR THIS CORE CONTRACT
BUT OTHER CORE CONTRACTS WE DID
HAVE SOME AVAILABILITY IN
FUNDING WHERE WE ARE ABLE TO
SUPPORT OTHER INVESTIGATORS FOR
THEIR RESEARCH AND THEIR GRANTS.
>> OTHER QUESTIONS?
WE ARE IN THE HOME STRETCH HERE.
FAS EVERYONE COULD REMEMBER TO
VOTE.
EARLY AND OFTEN OR AS OFTEN AS
APPROPRIATE WOULD BE GREAT.
THANK YOU.
LAST PRESENTATION IS BY DR.
MILTON MACIEL, EXTRA QUALITY
ASSURANCE PROGRAM OVERSIGHT
LABORATORY OR EQAPOL.
DR. MACIEL.
>> THANK YOU SO MUCH.
GOOD AFTERNOON, MY NAME IS MIL
MACIEL, PROGRAM OFFICER WITH
DIVISION OF (INAUDIBLE) EXTERNAL
QUALITY ASSURANCE PROGRAM
OVERSIGHT EQAPOL FOR SHORT.
EQAPOL OVERARCHING OBJECTIVE IS
MAINTAIN FACILITY SUPPORT THE
DEVELOPMENT IMPLEMENTATION AND
OVER SIGHT OF EXTERNAL QUALITY
ISSUE PROGRAMS TO MONITOR
LABORATORIES PERFORMING HIV AIDS
RESEARCH AND VACCINE TRIALS.
EQAPOL IS A CONTRACT AND SECOND
RENEWAL SINCE INCEPTION 2010
WITH ITERATION OF 7 YEARS AND IF
APPROVED WE EXPECT TO MAKE ONE
AWARD.
TO MAKE CLEAR THIS EQAPOL, I'M
SHOWING THE PORTFOLIO OF
CONTRACTS THAT ASSIST DAIDS AND
OVERSEEN QUALITY OF LABORATORY
TESTS FOR DIVISION ACTIVITY TBQA
AND I WILL GIVE AN EXAMPLE OF
KNOWLEDGE PROGRAM FOCUS ON
PROVIDING EFFICIENCY TESTS AND
MEASUREMENTS AND
CRYOPRESERVATION.
NEXT SLIDE.
NOW, EQAPOL MISSION ARE FOCUS ON
SPECIALIZED ASSAY WITH
PROFICIENCY PROGRAMS THAT ENSURE
COMPARABILITY AMONG MULTIPLE
LABORATORIES TESTING MULTIPLE
VACCINE CANDIDATES, AS WELL AS
CROSS POPULATION COMPARISON.
WITH THAT, EQAPOL SERVES AS
MECHANISM TO PROVIDE RESPONSIVE
REGULATORY AGENCIES THE FDA
RAISE CONFIDENCE INDIVIDUAL
LABORATORIES ARE GENERATING DATA
WITH RIGOR TO SUPPORT NEW
VACCINE FORMULATION ADVANCEMENT.
THESE ACTIVITIES ASSURE DECISION
MAKERS THAT RESULT RELIABLE AND
ACCURATE AND ENABLE DATA
COMPARISON AND PRIORITIZATION OF
THE BEST IMMUNOGENS.
EQAPOL CONTRACTED ACTIVITIES CAN
BE DIVIDED IN QUALITY ASSURANCE
AND OPERATION OF ACTIVITIES.
WITHIN THE QUALITY ASSURANCE
ACTIVITIES WE FIND THAT
PROFICIENCY TASKS AND PROGRAMS
SUCH AS ELISPOT FLOW CYTOMETRY,
MENTIONED, LUMINX, NEUTRALIZING
ANTIBODIES AND THE HIV INCIDENCE
ASSAY.
I WILL GIVE MORE DETAIL ABOUT
SOME OF THE PROGRAMS IN THE NEXT
SLIDE.
ANOTHER IMPORTANT PRESUMPTION IS
BIODIVERSITY WHICH PROCURES HIV
PANELS WHICH WILL SHOW MORE
ABOUT LATER ON.
EQAPOL HOLDS REPOSITORY OF
PBMCs WHICH CAP ACCREDITED.
THOSE ARE AVAILABLE UPON REQUEST
FOR DIFFERENT PURPOSES SUCH AS
ASSAY DEVELOPMENT.
FOR ALL PROBLEMS EQAPOL
MAINTAINS A DATABASE ACCESSIBLE
BY PARTICIPANTS.
OTHER OPERATIONAL ACTIVITIES
EQAPOL OFFERS A DEVICE ASSAY
VALIDATION REGULATORY COMPLIANCE
STATISTIC ISSUES.
ADDITIONALLY EQAPOL WORKS ON THE
OPTIMIZATION OF TRANSFERENCE OF
METHODOLOGIES BETWEEN
LABORATORY, AS WELL AS
DEVELOPMENT OF VALIDATION
PROGRAMS FOR NOVEL ASSAYS.
I JUST LEAVE YOU WITH THIS LINK
SO YOU CAN LOOK FOR ALL THIS
INFORMATION.
WORLDWIDE EQAPOL SERVES 78
UNIQUE SITES THAT PARTICIPATE ON
ONE OR MORE OF THE PROFICIENCY
PROGRAMS AS CAN BE SEEN OVER ON
THE TABLE ON THE LEFT.
THE MAP ON THE RIGHT GIVES A
PERSPECTIVE EQAPOL PRESENCE OF
NOTABLE INSTITUTION THAT
PARTICIPATE IN PROFICIENCY
PROGRAMS.
FOR EXAMPLE, BETWEEN SITES
SEATTLE AND CAPE TOWN OR U.S.
MILITARY PROGRAMS IN SILVER
SPRING AND THAILAND.
EACH OF THE FIVE PROFICIENCY
PROGRAMS WHICH CAN BE SEEN ON
THE LEFT ARE GOING UNDER EQAPOL
OFFERS PARTICIPANTS TWO SEND
OUTS PER YEAR WHICH INCLUDE MILY
CHARACTERIZED SPECIMENS IN ASSAY
REAGENTS, COMPLETION OF THE
TESTING ROUND EACH SITE RECEIVES
A REPORT THAT INCLUDES A SCORE
AND PERFORMANCE RATING.
THIS CORE CAN BE FROM POOR TO
EXCELLENT AS YOU CAN SEE IN THE
FIGURE BELOW.
WHEN NECESSARY SCORES FAIR
REAGENT SERVICES TO IMPROVE
ASSAY PERFORMANCE AND
OPPORTUNITY TO REPEAT
PROFICIENCY TESTS.
NEXT SLIDE.
THE VIRAL DIVERSE PROGRAM IS
FOCUS ON ESTABLISHING A SET OF
-- FULLY CHARACTERIZED VIRUS
FROM EARLY ACUTE HIV INFECTION
CONSISTENT WITH DEGREE OF
VARIABLE SOLUTION.
THIS HAS SEVERAL APPLICATIONS
SUCH AS DEVELOPMENT OF NEW
ASSAYS, VALIDATION OF ASSAY
PLATFORMS, ASSIST REGULATORS ON
EVALUATION OF THE TASK KITS.
MORE PERFORMANCE OF HIV DRUG
RESISTANCE, INFORM VACCINE
DEVELOPMENT AND MONOCLONAL
ANTIVIRAL TRIALS.
AND PARTICIPATE IN CBER EMERGING
VIRAL PANEL, WHICH IS DIVERSE
RANGE OF UNIQUE CIRCULATING
FORMS.
NEXT.
OF NOTE, EQAPOL PROVE TO BE
EXTREMELY FLEXIBLE IN RESPONSE
WITH UNFORESEEN SECRETIONS SUCH
AS SARS COV-2 PANDEMIC.
HERE I WANTED TO HIGHLIGHT SARS
COV-2 ANTIBODY ASSAY MONITORING
OR SAM FOR SHORT.
IN RESPONSE TO THE URGENT NEED
TO DEVELOP SAFE EFFECTIVE
VACCINES IMMUNOTHERAPEUTICS
AGAINST COVID-19.
THE SAAM PROGRAM SUPPORT R
RELIABLE TRANSFERENCE OF
METHODOLOGIES METHOD DOLL GISTS
FROM INNOVATOR AWARDS TO
CONTRACT RESEARCHER TO ASSESS
VACCINE RESPONSE WHICH GUARANTEE
RESULTS COULD BE USED FOR SUN
MISSION TO THE FDA AND TO
INVESTIGATE CORRELATES OF
PROTECTION.
THESE PROGRAMS HAPPENS BIMONTHLY
AS YOU CAN SEE IN THE TABLE
BELOW AND ALSO YOU SEE NUMBER OF
PARTICIPANTS AND THE SPORES
RETAINED.
THE OTHER PROBLEM THAT WAS ALSO
SUPPLEMENTED BY EQAPOL WAS THE
SARS COV-2 NEUTRALIZING ASSAY
COMPONENTS ASSAY.
WHICH EVALUATES PERFORMANCE AND
CONCORDANCE OF LARGE NUMBER OF
LIVE VIRUS AND AUTHORIZATION
ASSAYS H 2 INHIBITION ASSAY AND
LABORATORIES IN CONTRACT
RESEARCHER IMMUNIZATIONS.
THROUGH THE CONTRACT MAINTAINED
TO USE EQAP OXL AS RESOURCE TO
RESPOND TO THE EVOLVEK SITES,
CREATING AS GENETIC AS POSSIBLE
WITH THE LANGUAGE EQAPOL CAN BE
RESPONSIVE TO THE DEVELOPMENT OF
NEW STATE OF THE ART ASSAYS,
THAT PROVIDE ASSISTANCE BASED ON
UTILIZATION VALIDATION AND
DEVELOPMENT OF PROFICIENCY
PROGRAMS.
THE NEW PROJECTS COULD BE
CONSIDERED FOR THE CONTRACT
RENEW ARE TWO FULLY HELPER CELLS
WHICH IS IMPACT IS ONGOING AND
FOCUSED ON DEVELOPING A
CONSENSUS STAINING PROTOCOL
PHENOTYPIC FUNCTIONAL MARKERS TO
IDENTIFY CELLS IN HUMAN
PROLIFERATIVE CONSEQUENTLY
ASSEMBLY PANEL OF REAGENTS
SAMPLES FOR THE DISTRIBUTION
LABORATORIES STUDYING TFH.
ALSO CONSIDER EXPANSION INCLUDE
OPTIMIZATION AND STANDARDIZATION
AND UPDATED ANALYSIS.
OMICS RELATED TO VACCINE
RESPONSE, WHICH SHOULD INCLUDE
DEVELOPMENT OF THE AGENT AND
POTENTIALLY EVOLVE TO NEW EQA
PROGRAM AS IT IS CLEAR
CORRELATES OF HIV VACCINE WILL
INCLUDE MANY PARAMETERS.
FINALLY, DATA CURATION ANALYSIS
WHICH IMPROVE TO BE TIMELY
GIVING NEW NIH DATA MANAGEMENT
AND SHARING POLICIES.
WHICH WILL HAVE ASSAY
UTILIZATION DATA FORMTY AND
METADATA AND COMBINE DATA
SUPPORT DATA SHARING.
AMONG E QAPOL OVERSIGHT
LABORATORY, DEDICATED PROGRAM OF
-- WITH MANAGEMENT STAFF, WEB
BASE APPLICATION TO SUPPORT ALL
ACTIVITIES, THE REMEDIATION
SERVICES REFERRED TO BEFORE AND
OF COURSE AS DEMONSTRATED IN
SARS COV-2 PANDEMIC THE
FLEXIBILITY ON THAT PROGRAM.
THIS INITIATIVE WAS REVIEWED BY
PROFESSORS GOLDBURG AND FRANK
AND BOTH WERE SUPPORTIVE FROM
THEIR COMMENTS NOT ONLY THE
PROGRAM IS ESSENTIAL FOR VACCINE
DEVELOPMENT BUT ALSO KEY FOR THE
ADVANCEMENT OF COVID-19
VACCINES.
WE ALSO RECEIVED SOME COMMENTS
WHICH I WANT TO ADDRESS, THAT
THE PROGRAM SHOULD PLAN FOR
MAINTAINING IMPLEMENTATION
WITHSTANDING GLOBAL PROFICIENCY
TESTING, WHICH SHOULD BE
REQUIREMENT FOR APPLICATION.
WE AGREE WITH THAT.
AND ALL SITES PARTICIPATING
NIAID DAIDS HIV OR AIDS CLINICAL
TRIALS,S MUST ENROLL EQAPOL IN
RELATED DAIDS WHICH SNAILLY
LCONDUCTED INCLINICAL TRIALS.
WE HAVE SEEN UPWARD TREND IN
ENROLLMENT IN COMMERCIAL
LABORATORIES.
THE OTHER COMMENT WAS
CHARACTERIZE VIRUS OF THE VIRAL
DIVERSE PROGRAM IN ANTICIPATION
INTERNATIONAL LOCATION TO OTHER
HIV PREVENTION STUDIES.
LIKELY TO BE PLANNED THUS
CREATING A TESTING AGENT SUCH AS
NEUTRALIZING ANTIBODIES AGAINST
THE LEAD CAUSE SPECIES PRIOR TO
STUDY ONSET AND WE AGREE WITH
THAT AND IN FACT EQAPOL THROUGH
ITS WORLD PRESENCE WHERE
CLINICAL TRIALS TAKE PLACE AND
GOAL PROVIDE VIRUS PANELS FOR
TESTING OF PROPHYLACTIC MEASURES
IN VACCINES IN MONOCLONAL
DEVICE.
ANOTHER EXAMPLE IS EQAPOL IS
MAKING PANELS OF VIRUSES FROM
THE AMP PLACEBO EFFECTIVE
SUBJECTS.
WITH THAT, IS MY FINAL SLIDE,
APPROVED FOR THIS NEW WHICH HAS
DURATION OF SEVEN YEARS AND WE
EXPECT TO MAKE ONE AWARD.
THANK YOU SO MUCH.
THANK YOU FOR THE REVIEWERS FOR
HELPFUL COMMENTS.
GLAD TO ANSWER ANY QUESTIONS.
>> THANK YOU, DR. MACIEL.
COMMENTS OR QUESTIONS ON THE
EQAPOL EFFORT AND PROGRAM?
ANY QUESTIONS?
LET ME ASK PEOPLE AGAIN TO GO TO
YOUR ELECTRONIC COUNCIL BOOKS
AND PLEASE VOTE.
REOPEN THEM IF THEY HAVE CLOSED
AN VOTE.
I THINK MAYBE ONE MORE ISSUE
CARL THAT YOU WANTED TO DEAL
WITH, BEFORE WE DO THAT I WILL
NOTE WE ARE AHEAD OF SCHEDULE SO
IF WE WERE IN THE NATCHER CENTER
WHICH WE AREN'T WE COULD USE
THAT TIME AND ALL GO DOWN TO THE
CAFETERIA WHERE THEY SUBSCRIBE
TO THE SOP FOR FREEZERS THAT DR.
TANK TOLD US ABOUT AND HAVE ICE
CREAM TO CELEBRATE THE BEGINNING
OF SUMMER BUT WE ARE NOT THERE.
SO YOU WILL HAVE TO GET ICE
CREAM WHERE YOU ARE AND MAYBE
SEPTEMBER 12 WE WILL PLAN THAT.
THAT WOULD BE MY VOTE.
DR. DIEFFENBACH, THERE WAS ONE
OTHER ISSUE.
LET ME ALSO BEFORE I HAND BACK
TO YOU, THANK EVERYONE FOR THEIR
PRESENTATION.
TREMENDOUS WORK THAT GOES INTO
THESE AS EVERYONE KNOWS AND
REALLY WELL THOUGHT OUT, WELL
PRESENTED, AND WE APPRECIATE
ALSO THE FEEDBACK FROM EVERYONE
ON ARAC AS PEOPLE KNOW DONE
USUALLY FOUR TO SIX WEEKS BEFORE
AND WE CAN SEE THE CHANGES THAT
HAVE BEEN MADE AND YOU SEE THE
COMMENTS MADE BY LOT OF
PRESENTATIONS I THINK ARE SO
CLEAR AND SO WELL DONE.
SO THANKS TO EVERYONE FOR THAT.
I WILL TURN IT OVER TO YOU, DR.
DIEFFENBACH.
>> THANK YOU DR. FREEBURG,
PLEASURE TO SIT AND LISTEN TO
TODAY'S MEETINGS.
THE LEVEL OF ENGAGEMENT WITH THE
COMMITTEE LIKE YOU WERE SAYING
BEFORE WE GET TO THIS POINT IS
SO CRITICAL.
IT GIVES THE COUNCIL A CHANCE TO
SEE SOMETHING AS IT IS BEING
GERMINATED AND HAVE A INPUT TO
IT.
THE WHOLE POINT OF CONSULTATION
IS IMPROVEMENT.
SO THANK YOU FOR THE COMMITTEE
FOR YOUR PERSISTENCE AND
PARTICIPATION IN OUR ACTIVITIES
AND MAKING THE PRODUCTS DAIDS
PRODUCES BETTER AND THANK YOU TO
THE STAFF THAT JUST DID
INCREDIBLE JOB TODAY.
WE DO HAVE ONE LAST PROCEDURAL
STEP WE NEED TO TAKE INTO
ACCOUNT.
WE HAVE TO TAKE AN ENBLOCK
ACTION AND ACCEPT THE
RECOMMENDATIONS FOR THE ENTIRE
PROCEEDINGS WITH VOICE VOTE.
DO I HAVE A MOTION TO APPROVE
ALL OF WHAT WAS DISCUSSED TODAY
AND ALREADY VOTED ON?
YES.
>> THANK YOU.
>> THEN DO I HAVE A SECOND?
>> SECOND.
>> THANK YOU.
CAN I HAVE THE -- EVERYBODY WHO
SAY YEAH FOR POSITIVES AND NAY
AND THEN TAKE IT FROM THERE.
IS EVERYBODY YEAH?
>> ANY NAYS?
AT ALL?
NOT HEARING ANY, WE HAVE NOW
ACCOMPLISHED THE ENBLOCK ACTION.
I WANT TO THANK YOU FOR YOUR
PARTICIPATION.
AND WITH ANY LUCK AT ALL, PAM
SENDS A NOTE TO EVERYONE PLEASE
MAKE SURE ALL YOUR FINAL VOTES
ARE IN THE ECB SO WE DON'T HAVE
TO COME AND HASSLE YOU.
THANK YOU ALL.
I HOPE YOUR WEATHER WHERE YOU
ARE IS AS NICE AS THE WEATHER IS
IN WASHINGTON TODAY.
TAKE CARE.
>> THANKS, EVERYBODY.
>> HAVE A GOOD SUMMER.
>> THANK YOU, BYE-BYE.