Henry M Jackson Foundation For The Advancement Of Military Medicine

US MILITARY HIV RESEARCH

ADDRESSING THE THREATS OF HIV AND EMERGING INFECTIOUS DISEASE TO THE MILITARY AND GLOBAL COMMUNITY THROUGH INNOVATIVE RESEARCH

HIV PROGRAM FOR PRESIDENTS EMERGENCY PLAN FOR AIDS RELIEF PEPFAR AWARD

RECIPIENT PROVIDES EXPERT, INNOVATIVE, AND RESPONSIVE OPERATIONAL SUPPORT OF DPAA EFFORTS TO LOCATE,RECOVER, AND IDENTIFY THE REMAINS OF UNACCOUNTED FOR DEPARTMENT OF DEFENSE DOD PERSONNEL FROM DESIGNATED PAST CONFLICTS. DPAA MISSION INVOLVES HISTORICAL RESEARCH, ARCHAEOLOGY,FORENSIC ANTHROPOLOGY,LABORATORY ANALYSES,AND OTHER RELATED ACTIVITIES

ESTABLISHMENT OF THE COLLABORATIVE HEALTH INITIATIVE RESEARCH PROGRAM (CHIRP)

RESEARCH AND DEVELOPMENT OF PROTECTIVE VACCINES AND OTHER COUNTERMEASURES AGAINST INFECTIOUS DISEASE AGENTS OF MILITARY IMPORTANCE AWARD

MURTHA CANCER CENTER TRANSLATIONAL CLINICAL RESEARCH: APPLIED PROTEOGENOMICS ORGANIZATIONAL LEARNING AND OUTCOMES (APOLLO)AND FRAMINGHAM CORE

UNIFORMED SERVICES UNIVERSITY (USU) AND UNIVERSITY OF CALIFORNIA SAN FRANCISCO (UCSF) PARTNERSHIP FOR DEVELOPMENT OF CHRONIC TRAUMATIC ENCEPHALOPATHY (CTE) THERAPEUTICS

UNIFORMED SERVICES UNIVERSITY (USU) AND UNIVERSITY OF CALIFORNIA SAN FRANCISCO (UCSF) PARTNERSHIP FOR DEVELOPMENT OF CHRONIC TRAUMATIC ENCEPHALOPATHY (CTE) THERAPEUTICS

BASE AWARD FOR AUSTERE ENVIRONMENTS CONSORTIUM FOR ENHANCE SEPSIS OUTCOMES (ACESO) AWARD

MURTHA CANCER CENTER TRANSLATIONAL RESEARCH PROGRAM

UCSF/USUHS PARTNERSHIP TO DEVELOP TAU PRION THERAPEUTICS FOR CHRONIC TRAUMATIC ENCEPHALOPATHY

MURTHA CANCER TRANSLATIONAL CLINICAL RESEARCH: APPLIED PROTEOGENOMICS ORGANIZATIONAL LEARNING AND OUTCOMES (APOLLO) AND FRAMINGHAM - FY24 CORE

MILITARY TRAUMATIC BRAIN INJURY (MTBI-2) INITIATIVE - RESEARCH COLLABORATION

BREAST CANCER OF EXCELLENCE (BC-COE) CLINICAL BREAST CARE PROJECT (CBCP)

BRAIN INJURY AND DISEASE PREVENTION, TREATMENT, AND RESEARCH - FY CORE

NATIONAL EMERGENCY MEDICAL SERVICES & 911 PROJECTS TO SUPPORT POST-CRASH CARE

WOUNDED WARRIOR SERVICE DOG PROGRAM WWSDP

BREAST CANCER OF EXCELLENCE (BREAST-COE) CORE

RED HILL WATER REGISTRY

GYNECOLOGIC CANCER - CENTER OF EXCELLENCE (GYN-COE)

LEVERAGING TRAUMA CRITICAL CARE RESEARCH FOR THE DEVELOPMENT OF CLINICAL DECISION SUPPORT TOOLS IN SUPPORT OF THE SURGICAL CRITICAL CARE INITIATIVE (SC2I)

BRAIN INJURY AND DISEASE PREVENTION, TREATMENT, AND RESEARCH CORE

ADVANCEMENT OF VACCINES AND THERAPIES FOR HENIPAVIRUSES

PROSTATE DISEASE RESEARCH

NATIONAL CENTER FOR DISASTER MEDICINE AND PUBLIC HEALTH (NCDMPH) NATIONAL DISASTER MEDICAL SYSTEM PILOT PHASE IV

CANCER MOONSHOT 2

CENTER FOR NEUROSCIENCE AND REGENERATIVE MEDICINE (CNRM)

COMBAT AND TRAINING QUERYABLE EXPOSURE EVENT REPOSITORY (CONQUER)-2

MURTHA CANCER TRANSLATIONAL CLINICAL RESEARCH: FRAMINGHAM LONGITUDINAL STUDY AND APPLIED PROTEOGENOMICS ORGANIZATIONAL LEARNING AND OUTCOMES (APOLLO)- FY22 CORE

MURTHA CANCER CENTER RESEARCH PROGRAM (MCCRP): FRAMINGHAM LONGITUDINAL STUDY AND APPLIED PROTEOGENOMICS ORGANIZATIONAL LEARNING AND OUTCOMES (APOLLO)

CENTER FOR REHABILITATION SCIENCES RESEARCH

PROJECT 1: PRAGMATIC ASSESSMENT OF INFLUENZA VACCINE EFFECTIVENESS IN THE DOD (PAIVED) PROJECT 2: COVID-19: 1) EPIDEMIOLOGY, IMMUNOLOGY AND CLINICAL CHARACTERISTICS OF EMERGING INFECTIOUS DISEASES WITH PANDEMIC POTENTIAL (EPICC-EID) 2) MILITARY REGISTRY ANALYSIS PROJECT (COVID M-RAP) 3)THE OBSERVATIONAL SEROEPIDEMIOLOGIC STUDY OF COVID-19 AT THE UNITED STATES NAVAL ACADEMY (TOSCANA)

PROGRAM PROJECT AWARDS

CENTER FOR NEUROSCIENCE AND REGENERATIVE MEDICINE (CNRM)

AIRMAN READINESS MEDICAL RESEARCH (ARMR) PROGRAM

BRAIN INJURY AND DISEASE PREVENTION, TREATMENT, AND RESEARCH

"COVID-19". COVID-19 - 1) EPIDEMIOLOGY, IMMUNOLOGY AND CLINICAL CHARACTERISTICS OF EMERGING INFECTIOUS DISEASES WITH PANDEMIC POTENTIAL (EPICC-EID) 2) ADAPTIVE COVID-19 TREATMENT TRIAL(ACTT)

CENTER FOR THE STUDY OF TRAUMATIC STRESS (CSTS)

APPLIED PROTEOGENOMICS ORGANIZATIONAL LEARNING AND OUTCOMES (APOLLO) - FY23 CORE

COMPUTATIONAL BIOLOGY INITIATIVE FOR MILITARY MEDICINE

A RESEARCH COLLABORATORY TO EXPLORE BEST PRACTICES FOR EXPANDING ACCESS TO CARE THROUGH THE EXPANSION AND SUPPORT OF TELEHEALTH CARE FOR CHILDREN AND FAMILIES WITH BEHAVIORAL HEALTH NEEDS

"COVID-19". DOD COVID-19 RAPID EVALUATION AND STUDY OF THE PANDEMIC OUTBREAK NATIONALLY BY SUSTAINING AND LEVERAGING PROLONGED FIELD CARE RESEARCH EFFORTS

A RESEARCH COLLABORATORY TO EXPLORE BEST PRACTICES FOR EXPANDING ACCESS TO CARE THROUGH THE EXPANSION AND SUPPORT OF TELEHEALTH CARE FOR CHILDREN AND FAMILIES WITH BEHAVIORAL HEALTH NEEDS

CENTER FOR PROSTATE CANCER (CPDR)

RESEARCH AND DEVELOPMENT OF OPERATIONAL AND UNDERSEA MEDICAL ISSUES OF MILITARY IMPORTANCE

CENTER FOR NEUROSCIENCE AND REGENERATIVE MEDICINE (CNRM)FY21 CORE PROGRAM

CONSORTIUM FOR HEALTH AND MILITARY PERFORMANCE (CHAMP), HUMAN PERFORMANCE RESOURCE CENTER (HPRC), AND OPERATION SUPPLEMENT SAFETY (OPSS)

BRAIN INJURY AND DISEASE PREVENTION, TREATMENT, AND RESEARCH

BRAIN INJURY AND DISEASE PREVENTION, TREATMENT, AND RESEARCH - FY24 CORE

BRAIN INJURY AND DISEASE PREVENTION, TREATMENT, AND RESEARCH - FY22 CORE

SERVICE ACADEMY LONGITUDINAL MTBI OUTCOMES STUDY (SALTOS)

HOLISTIC HEALTH AND FITNESS (H2F)

STUDY TO ASSESS RISK AND RESILIENCE IN SERVICEMEMBERS (STARRS 3)

COMPARATIVE ADJUVANT STUDY FOR DNA/PROTEIN PRIME/BOOST HIV-1 VACCINE

NATIONAL GUARD BUREAU JOINT STAFF PREVENTION WORKFORCE SUPPORT PROJECT

COMPARATIVE EFFECTIVENESS & PROVIDER INDUCED DEMAND COLLABORATION (EPIC) CLINICAL & ECONOMIC ANALYSIS VARIATION IN HEALTHCARE

UNITED STATES MILITARY HIV RESEARCH PROGRAM (MHRP) CLINICAL TRIALS UNIT

CENTER FOR STUDY OF TRAUMATIC STRESS (CSTS) PROGRAM

CANCER MOONSHOT 2

MASTERS AND PH.D I HEALTH PROFESSIONS EDUCATION PROGRAM AND LONG-TERM /CAREER STUDY (LTCOS)

CANCER MOONSHOT 2

CENTER FOR NEUROSCIENCE AND REGENERATIVE MEDICINE (CNRM) RESEARCH PROJECTS FY22 CORE

NATIONAL GUARD BUREAU STAR BEHAVIORAL HEALTH PROVIDER EXPANSION PROGRAM

THE MILITARY TRAUMATIC BRAIN INJURY INITIATIVE (MTBI-2) CORE

THE GONORRHEA VACCINE COOPERATIVE RESEARCH CENTER

RESEARCH ACCELERATING MILITARY PEDIATRICS (RAMP)

COMPUTATIONAL INJURY DETECTION AND PREVENTION INITIATIVE FOR MILITARY MEDICINE

DEPLOYMENT PSYCHOLOGY COLLABORATION & TRAINING FOR BEHAVIORAL HEALTH CONSULTANTS WORKING IN PRIMARY CARE SETTINGS

AFRRI/NIAID IAA 2015

COLLABORATIVE CLINICAL RESEARCH ACTIVITIES/INFECTIOUS DISEASE CLINICAL RESEARCH PROGRAM (IDCRP)/DEFENSE HEALTH PROGRAM (DHP) CORE

INFECTIOUS DISEASE CLINICAL RESEARCH PROGRAM (IDCRP)DEFENSE HEALTH PROGRAM (DHP) FY23 CORE

COMPUTATIONAL INITIATIVE FOR PERFORMANCE MONITORING

BREAST CANCER OF EXCELLENCE (BREAST-COE) FY24 CORE

BREAST CANCER OF EXCELLENCE (BREAST-COE) FY23 CORE

SUICIDE AVOIDANCE FOCUSED ENHANCED GROUP USING ALGORITHM RISK DETECTION (SAFEGUARD)

BREAST CANCER CENTER OF EXCELLENCE (BREAST-COE)

BREAST CANCER OF EXCELLENCE (BREAST-COE) FY22 CORE

WOUNDX CLINICAL DECISION SUPPORT TOOL

COLLABORATIVE CLINICAL RESEARCH ACTIVITIES

LEVERAGING TRAUMA CRITICAL CARE RESEARCH FOR THE DEVELOPMENT OF CLINICAL DECISION SUPPORT TOOLS IN SUPPORT OF THE SURGICAL CRITICAL CARE INITIATIVE (SC2I)

MILITARY NUTRITION ENVIRONMENT

THE AMERICAN GENOME CENTER (TAGC-6)

GYNECOLOGIC CANCER-CENTER OF EXCELLENCE (GYN-COE) CORE

GYNECOLOGIC CANCER-CENTER OF EXCELLENCE (GYN-COE) CORE

SC2I RESEARCH - DEVELOPMENT OF CLINICAL DECISION SUPPORT TOOLS

CENTER FOR DEPLOYMENT PSYCHOLOGY (CDP) CORE

CANCER MOONSHOT 2

SURGICAL CRITICAL CARE INITIATIVE (SC2I) FY 21 CORE

SURGICAL CARE INITIATIVE (SC2I) BIOLOGY DRIVEN CRITICAL CARE

CONSORTIUM FOR HEALTH AND MILITARY PERFORMANCE (CHAMP): HUMAN PERFORMANCE RESOURCE CENTER(HPRC) AND OPERATION AND SUPPLEMENT SAFETY (OPSS)

GYNECOLOGICAL CANCER CENTER OF EXCELLENCE (GYNCOE)

MURTHA CANCER CENTER INFRASTRUCTURE CORE

A PHASE I/IIA CLINICAL TRIAL TESTING THE SAFETY AND IMMUNOGENICITY OF A HEROIN VACCINE AND ITS EFFICACY AGAINST MORPHINE CHALLENGE.

COLLABORATIVE CLINICAL RESEARCH ACTIVITIES/INFECTIOUS DISEASE CLINICAL RESEARCH PROGRAM (IDCRP) CORE

PROSTATE DISEASE RESEARCH &#8208 FY23 CORE

PROSTATE DISEASE RESEARCH CORE

CENTER FOR PROSTATE DISEASE RESEARCH (CPDR) - FY20 CORE

BATTLEFIELD SHOCK AND ORGAN SUPPORT (BSOS) RESEARCH PROGRAM

USU INTRAMURAL RESEARCH PROGRAM

ASSESSING DOMESTIC PRODUCTION OF PHARMACEUTICAL PRODUCTS FOR THE MILITARY HEALTH SYSTEM

INTEGRATED HEALTH RESEARCH FOR MEDB CONDITIONS IN CHILDREN

ELUCIDATING THE ROLE OF INCREASED NEUROINFLAMMATION AND RELATED STRUCTURAL AND FUNCTIONAL NEUROLOGICAL SEQUELAE AFTER EXPOSURE TO REPETITIVE BLAST

NATIONAL FOOTBALL LEAGUE (NFL) AUGMENTATION OF THE CONCUSSION ASSESSMENT, RESEARCH AND EDUCATION(CARE)- SERVICE ACADEMY LONGITUDINAL MTBI OUTCOMES STUDY (SALTOS) INTEGRATED STUDY

MILITARY WOMEN'S HEALTH RESEARCH CONSORTIUM

BLENDED LEARNING IN CLINICAL ANATOMY EDUCATION COLLABORATIVE RESEARCH

RESEARCH TRAINING AND INNOVATION (RTI)AWARD

CENTER FOR DEPLOYMENT PSYCHOLOGY (CDP) CORE PROGRAM THE NATIONAL GUARD BUREAU STAR BEHAVIORAL HEALTH PROVIDERS EXPANSION PROGRAM BEYOND THE YELLOW RIBBON (BYR) OREGON STAR BEHAVIORAL HEALTH PROGRAM TRAINING IN BRIEF BEHAVIORAL TREATMENT FOR INSOMNIA AND SUICIDE PREVENTION

STUDY TO ASSESS RISK AND RESILIENCE IN SERVICEMEMBERS LONGITUDINAL STUDY (STARRS-LS) COLLABORATION

STUDY TO ASSESS RISK AND RESILIENCE IN SERVICEMEMBERS - LONGITUDINAL STUDY (STARRS-LS) COLLABORATION

INVESTIGATING TRAINING ASSOCIATED BLAST PATHOLOGY (INVICTA)

THE ATLANTIC COAST SEXUALLY TRANSMITTED INFECTION COOPERATIVE RESEARCH CENTER (AC

INTEGRATIVE CARDIAC HEALTH PROJECT (ICHP)

STUDY TO ASSESS RISK AND RESILIENCE IN SERVICE MEMBERS LONGITUDINAL STUDY (STARRS-LS)

ACCELERATED EMERGENCE FROM ANESTHESIA WITH CAFFEINE ADMINISTRATION (OYE 2024)

TARGETING HIV RESERVOIRS IN CHILDREN WITH HIVIS DNA AND MVA-CMDR VACCINES

GET BETTER TOGETHER: A PRIMARY PREVENTION INTERVENTION FOR MILITARY COUPLES

CENTER FOR DEPLOYMENT PSYCHOLOGY (CDP) - CORE PROGRAM

ARMY NATIONAL GUARD BEHAVIORAL HEALTH SUPPORT PROJECT

MILITARY HEALTH SYSTEM RESPONSE TO COVID-19: A HEALTH SERVICES RESEARCH APPROACH TO SUSTAINABLE PROCESS IMPROVEMENTS

ADEPT: ADAPTIVE TRIAL FOR THE TREATMENT OF DEPRESSIVE SYMPTOMS ASSOCIATED WITH CONCUSSION USING REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION PROTOCOLS

AFRRI GOOD LABORATORY PRACTICES (GLP) PROJECT

NATIONAL GUARD BUREAU STAR BEHAVIORAL HEALTH PROVIDER EXPANSION PROGRAM-FY'23

ASSESSMENT AND MAINTENANCE OF GENERAL SURGERY EXPEDITIONARY COMPETENCY AND CURRENCY

THE AMERICAN GENOME CENTER

INFECTIOUS DISEASES CLINICAL RESEARCH PROGRAM (IDCRP) DEFENSE HEALTH PROGRAM (DHP) FY25 CORE

A PHASE 1 SINGLE DOSE CROSSOVER STUDY OF KETAMINE INTRANASAL SPRAY VERSUS KETAMINE INTRAVENOUS INJECTION VERSUS KETAMINE INTRAMUSCULAR INJECTION UNDER FASTED CONDITIONS

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL EVALUATING THE EFFICACY OF NON-ANTIBIOTIC OTC PRODUCTS IN THE PREVENTION OF

CENTER FOR STUDY OF TRAUMATIC STRESS (CSTS) PROGRAM

FY25 CENTER FOR DEPLOYMENT PSYCHOLOGY

PURPOSE: TO SUPPORT THE UTILIZATION OF CREATIVE ARTS THERAPIES AND NON-CLINICAL ARTS ENGAGEMENT AND TO SUPPORT BEST PRACTICES IN ARTS HEALTH AND WELL-BEING ACROSS THE CREATIVE FORCES DEPARTMENT OF WAR AND VETERANS AFFAIRS CLINICAL SITES.

PURPOSE: TO SUPPORT THE UTILIZATION OF ARTS IN HEALTHCARE SETTINGS AND SUPPORT BEST PRACTICES IN ARTS HEALTH AND WELL-BEING ACROSS THE CREATIVE FORCES DEPARTMENT OF DEFENSE AND VETERANS AFFAIRS CLINICAL SITES.

A RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED, CLINICAL TRIAL OF THE SAFETY, EFFICACY, AND DURABILITY OF MDMA-ASSISTED THERAPY FOR MILITARY SERVICE MEMBERS WITH PTSD

A PROOF OF CONCEPT, RANDOMIZED, CONTROLLED STUDY OF TUBERCULOSIS IMMUNIZATION WITH BCG TO PREVENT INFECTION IN HEALTHY ADULTS (TIPI TRIAL)

PRAGMATIC ASSESSMENT OF INFLUENZA VACCINE EFFECTIVENESS IN THE DOD (PAIVED)

ASSESSING THE SECURITY AND QUALITY OF THE UNITED STATES (US) MILITARY HEALTH SYSTEM PHARMACEUTICAL SUPPLY CHAIN: A PILOT STUDY

PRECISION GENOMICS IMPLEMENTATION FOR ETIOLOGIES OF SUDDEN DEATH AND ALL-CAUSE MORTALITY

A COLLABORATIVE STUDY OF THE FEASIBILITY OF AND BEST PRACTICES FOR EXPANDING TELEHEALTH CARE FOR CHILDREN AND FAMILIES WITH BEHAVIORAL HEALTH NEEDS

A COLLABORATIVE STUDY OF THE FEASIBILITY OF AND BEST PRACTICES FOR EXPANDING TELEHEALTH CARE FOR CHILDREN AND FAMILIES WITH BEHAVIORAL HEALTH NEEDS

FETAL ALCOHOL SPECTRUM DISORDERS PREVENTION AND CLINICAL GUIDELINE

PURPOSE: TO SUPPORT THE UTILIZATION OF ARTS IN HEALTHCARE SETTINGS AND SUPPORT BEST PRACTICES IN ARTS, HEALTH, AND WELL-BEING ACROSS THE CREATIVE FORCES DEPARTMENT OF DEFENSE AND VETERANS AFFAIRS CLINICAL SITES.

WARFIGHTER READINESS: OPTIMIZING HUMAN PERFORMANCE

FETAL ALCOHOL SPECTRUM DISORDERS PREVENTION AND CLINICAL GUIDELINES RESEARCH

RESOLVING THE BURDEN OF LOW BACK PAIN IN MILITARY SERVICE MEMBER AND VETERANS...

PERIOPERATIVE NUTRITION OPTIMIZATION FOR REDUCING COMPLICATIONS AFTER SURGICAL FRACTURE FIXATION

PRAGMATIC ASSESSMENT OF INFLUENZA VACINE EFFECTIVENESS IN THE DOD (PAVIED) - IDCRP

ELUCIDATING THE ROLE OF THE NEUROVASCULAR UNIT AND RELATED STRUCTURAL AND FUNCTIONAL NEUROLOGICAL SEQUELAE AFTER EXPOSURE TO REPEATED BLAST

THE AMERICAN GENOME CENTER (TAGC) - FY22 CORE

DEFENSE HEALTH PROGRAM (DHP) INFRASTRUCTURE PROGRAM

AFRRI/NIAID IAA

A PROGRAM OF EXTRACORPOREAL LIMB SALVAGE RESEARCH IN SUPPORT OF MULTIDOMAIN OPERATIONS

PURPOSE: TO SUPPORT THE UTILIZATION OF ARTS IN HEALTHCARE SETTINGS AND SUPPORT BEST PRACTICES IN ARTS HEALTH AND WELL-BEING ACROSS THE CREATIVE FORCES DEPARTMENT OF DEFENSE AND VETERANS AFFAIRS CLINICAL SITES.

ENHANCING WARFIGHTER SURVIVABILITY BY INVESTING IN MILITARY MEDICINE SURGICAL TEAMS SKILLS

USSOCOM BASELINING AND ASSESSMENT (SABRES)

CENTER FOR IMMUNOLOGICAL INTERVENTIONS AGAINST GONORRHEA (CIIG) - MODIFIED PROJECT SUMMARY/ABSTRACT SECTION SUMMARY OVER 82 MILLION NEISSERIA GONORRHOEAE (NG) INFECTIONS OCCUR GLOBALLY AND GONORRHEA RANKS SECOND AMONG NOTIFIABLE INFECTIONS REPORTED TO THE CDC. NG HAS A MAJOR IMPACT ON REPRODUCTIVE HEALTH, THE WELL-BEING OF NEWBORNS, AND THE TRANSMISSION OF THE HUMAN IMMUNODEFICIENCY VIRUS. CONTROL RELIES ON SAFE-SEX COUNSELING AND IDENTIFICATION AND TREATMENT OF INFECTED INDIVIDUALS, THE LATTER OF WHICH IS SERIOUSLY CHALLENGED BY THE RAPID EVOLUTION OF ANTIBIOTIC RESISTANCE IN NG. NEW INTERVENTIONS ARE NEEDED TO REDUCE THE NUMBER OF INFECTIONS AND CURB THE SPREAD OF RESISTANT STRAINS. THE OVERALL GOAL OF THE CENTER FOR IMMUNOLOGICAL INTERVENTIONS AGAINST GONORRHEA (CIIG) IS TO ADVANCE A PROMISING VACCINE CANDIDATE THROUGH FURTHER PRECLINICAL DEVELOPMENT AND INTO CLINICAL TRIALS. THIS GOAL WILL BE ACCOMPLISHED BY THREE RESEARCH PROJECTS THAT ARE FOCUSED ON DEVELOPING I.) A COMBINATION MENINGOCOCCAL OUTER MEMBRANE VESICLE (OMV) VACCINE (VESIVAX® IAMS-OMV-NGAG) CONTAINING PROMISING RECOMBINANT NG ANTIGENS USING THE VESIVAX® LIPOSOME VACCINE PLATFORM. THE OMV PORTION OF THE VACCINE IS DESIGNED TO INDUCE BROADER REACTIVITY AGAINST NG STRAINS; CO-DELIVERY OF SELECTED ADJUVANTS (IAMS) AND INTRADERMAL IMMUNIZATION THROUGH A PATENTED MICRONEEDLE PATCH WILL BE OPTIMIZED TO INDUCE ROBUST PROTECTIVE RESPONSES (PROJECTS 1 AND 3); II.) A PEPTIDE/VIRUS-LIKE PROTEIN IMMUNOGEN TO AUGMENT THE VESIVAX® IAMS-OMV-NGAG VACCINE BY INDUCING EPITOPE-TARGETED ANTIBODIES THAT INCREASE NG SUSCEPTIBILITY TO HOST IMMUNE DEFENSES BY BLOCKING MECHANISMS BY WHICH NG TO EVADES COMPLEMENT ACTIVATION (PROJECT 2). THREE COLLABORATIVE SCIENTIFIC CORES WILL SUPPORT THE PROJECTS BY PROVIDING STATE-OF-THE ART MEASUREMENTS OF IMMUNE RESPONSES (CORE B), IN VIVO EFFICACY TESTING IN MOUSE MODELS OF NG REPRODUCTIVE TRACT INFECTION (CORE C), AND CENTRALIZED SYSTEMS FOR DATA MANAGEMENT, STUDY DESIGN, DATA ANALYSIS, AND PRE-IND ACTIVITIES (CORE D). AN ADMINISTRATIVE CORE (CORE A) WILL PROVIDE THE INFRASTRUCTURE NEEDED TO FACILITATE COMMUNICATIONS BETWEEN THE CIIG AND NIH, AND COORDINATE TELECONFERENCES AMONG THE PROJECT AND CORE LEADERS TO FOSTER DATA EXCHANGE, INTERNAL PEER REVIEW AND INTRA-CENTER COLLABORATIONS. A STANDING SCIENTIFIC ADVISORY BOARD WILL REVIEW SCIENTIFIC PROGRESS EACH YEAR AND DETERMINE WHICH PRODUCTS WILL BE ADVANCED FOR FURTHER PRE-CLINICAL DEVELOPMENT. PRE-IND ACTIVITIES WILL BEGIN IN YEAR 4 UNDER A REGULATORY STRATEGY PROVIDED BY CORE D.

TO SUPPORT PLACEMENT AND SUSTAINMENT OF CREATIVE ARTS THERAPIES IN PATIENT-CENTERED CARE AT MILITARY AND VETERANS CLINICAL SITES AS WELL AS THROUGH A TELEHEALTH DELIVERY PROGRAM FOR PATIENTS IN REMOTE AREAS

CENTER FOR REHABILITATION SCIENCES RESEARCH (CRSR)

DEVELOPMENT OF JNJ-26366821 (TPOM) AS A PROPHYLACTIC RADIATION COUNTERMEASURE AS WELL AS A MITIGATOR (SHORTLY AFTER RADIATION)

PURPOSE: TO SUPPORT THE UTILIZATION OF ARTS IN HEALTHCARE SETTINGS AND SUPPORT BEST PRACTICES IN ARTS, HEALTH, AND WELL-BEING ACROSS THE CREATIVE FORCES DEPARTMENT OF DEFENSE AND VETERANS AFFAIRS CLINICAL SITES.

DEVELOPMENT OF MACHINE LEARNING MODELS UTILIZING MULTIMODAL ASSESSMENTS FROM SMART WEARABLES FOR ENHANCED POST-TRAUMATIC STRESS DISORDER (PTSD) SCREENING AND PRECISION DIAGNOSIS

LONG TERM CLINICAL CORRELATES OF ANOMALOUS HEALTH INCIDENTS: IMAGING, BIOMARKERS, AND CLINICAL PHENOTYPING PARAMETERS

FUNCTIONS OF POLO-LIKE KINASES DURING MAMMALIAN MEIOSIS

A PHASE II RANDOMIZED, OBSERVER-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS EFFICACY OF MENINGOCOCCAL GROUP B VACCINE RMENB+OMV NZ (BEXSERO)IN PREVENTING GONOCOCCAL INFECTION

EVALUATION OF ANTIBODY RESPONSES ELICITED BY ZIKA VACCINATION IN FLAVIVIRUS-NA?VE AND -EXPERIENCED INDIVIDUALS - PROJECT TITLE: EVALUATION OF ANTIBODY RESPONSES ELICITED BY ZIKA VACCINATION IN FLAVIVIRUS-NAÏVE AND - EXPERIENCED INDIVIDUALS PROJECT SUMMARY ZIKA VIRUS (ZIKV) IS A MEMBER OF THE FLAVIVIRUS GENUS THAT RECENTLY PRECIPITATED WIDESPREAD CASES OF NEUROLOGICAL PATHOLOGY AND CONGENITAL NEUROLOGIC DEFECTS. IN RESPONSE, A MULTILATERAL COALITION OF INVESTIGATORS DESIGNED AND DEVELOPED MULTIPLE VACCINE CANDIDATES THAT ELICITED POTENT ZIKV-NEUTRALIZING ANTIBODIES, WHICH WERE SHOWN TO CORRELATE WITH DISEASE PROTECTION IN ANIMAL MODELS. DESPITE THESE ADVANCES, IT REMAINS UNCLEAR HOW THE ZIKV IMMUNIZATION ANTIBODY RESPONSE IS SHAPED IN HUMANS WITH AND WITHOUT PRIOR EXPOSURE TO OTHER FLAVIVIRUSES, SUCH AS DENGUE VIRUS (DENV), JAPANESE ENCEPHALITIS (JEV) OR YELLOW FEVER VIRUS (YFV); PARTICULARLY AS THESE VIRUSES ALL HAVE SIGNIFICANT EPIDEMIOLOGIC OVERLAP WITH ZIKV. OUR LONG-TERM GOAL IS TO UNDERSTAND THE UNDERLYING HUMORAL MECHANISMS GENERATED BY FLAVIVIRUS VACCINATION, WHICH CAN PROVIDE LONG-TERM PROTECTION IN FLAVIVIRUS-NAÏVE AND/OR -EXPERIENCED POPULATIONS. SUCH INFORMATION WOULD GUIDE VACCINATION STRATEGIES IN FLAVIVIRUS-ENDEMIC AREAS OR AMONG FLAVIVIRUS-NAÏVE INDIVIDUALS TRAVELING TO ENDEMIC AREAS. THE OVERALL OBJECTIVE OF THIS PROPOSED RESEARCH IS TO EVALUATE THE SPECIFICITY AND FUNCTION OF THE B CELL REPERTOIRE ELICITED BY ZIKV VACCINATION IN FLAVIVIRUS- NAÏVE AND -EXPERIENCED INDIVIDUALS. TO ACHIEVE THESE GOALS, THIS RESEARCH WILL UTILIZE LEADING-EDGE TECHNOLOGIES TO SEQUENCE B CELL RECEPTORS (BCRS) FROM FLAVIVIRUS-SPECIFIC, SINGLE B CELLS USING RNASEQ AND NEXT GENERATION SEQUENCING (NGS). BCRS WILL BE COMPARED BETWEEN ZIKA VACCINATED INDIVIDUALS, AND TO PREVIOUSLY PUBLISHED MONOCLONAL ANTIBODIES, TO DETERMINE THE PREVALENCE OF B CELL LINEAGES, GENE ASSIGNMENT, DEGREE OF SOMATIC HYPERMUTATION (SHM), AND LENGTHS OF HEAVY CHAIN COMPLEMENTARY-DETERMINING REGION 3 (HCDR3). COMMON B CELL LINEAGES WILL BE EXPRESSED AS MONOCLONAL ANTIBODIES AND EVALUATED FOR THEIR SPECIFICITY, FUNCTION, STRUCTURAL, AND ABILITY TO PROTECT AGAINST FLAVIVIRUS CHALLENGES IN MOUSE MODELS. A TOTAL OF 40 SAMPLES WILL BE EVALUATED FROM INDIVIDUALS REPRESENTING 5 GROUPS IN 3 DIFFERENT PHASE I ZIKA VACCINE CLINICAL TRIALS: A) FLAVIVIRUS-NAÏVE INDIVIDUALS WHO WERE VACCINATED USING A ZIKA PURIFIED INACTIVATED WHOLE VIRUS VACCINE (ZPIV) B) FLAVIVIRUS-NAÏVE INDIVIDUALS WHO WERE VACCINATED WITH AN ADENO-VECTORED ZIKA M-E (AD26.ZIKV.M-ENV) C) INDIVIDUALS LIVING IN PUERTO RICO WITH PRIOR DENGUE INFECTION WHO WERE ZPIV VACCINATED D) JEV (IXIARO®) VACCINATED INDIVIDUALS WHO WERE ZPIV VACCINATED AND E) YFV (YV-VAX®) VACCINATED INDIVIDUALS WHO WERE ZPIV VACCINATED. FLAVIVIRUS-NAÏVE, ZIKA VACCINATED INDIVIDUALS (GROUPS A-B) WILL BE EXPLORED IN AIM 1 AND FLAVIVIRUS-EXPERIENCED INDIVIDUALS, EITHER BY PRIOR INFECTION (GROUP C) OR BY PRIOR VACCINATION (GROUPS D-E), WILL BE EXPLORED IN AIM 2. AIM 3 WILL EXAMINE A LATE TIMEPOINT (6 MONTHS) FOLLOWING THE LAST ZPIV VACCINATION TO DETERMINE THE LONGEVITY OF THE CIRCULATING B CELL LINEAGES CHARACTERIZED IN AIMS 1 AND 2. EVALUATING PREVALENT B CELL LINEAGES RESPONDING TO ZIKA VACCINATION WILL REVEAL THE SPECIFICITY, FUNCTION AND DURABILITY OF THE HUMORAL RESPONSE AMONG INDIVIDUALS LIVING IN DIFFERENT REGIONS. THESE STUDIES WILL PROVIDE INSIGHTS INTO THE POTENCY AND DURABILITY OF ZIKV VACCINE RESPONSES IN BOTH FLAVIVIRUS- NAÏVE AND -EXPERIENCED INDIVIDUALS AND MAY TRANSLATE INTO VACCINE STRATEGIES THAT YIELD LONG-LIVED PROTECTION.

VACCINE DURABILITY AND PREDICTORS OF IMMUNITY AND REACTOGENICITY

"COVID-19".TRANSFORMING TECHNOLOGY FOR THE WARFIGHTER (TTW) 4, POC DIAGNOSTIC

TO SUPPORT PLACEMENT AND SUSTAINMENT OF CREATIVE ARTS THERAPIES IN PATIENT-CENTERED CARE AT MILITARY AND VETERANS CLINICAL SITES AS WELL AS THROUGH A TELEHEALTH DELIVERY PROGRAM FOR PATIENTS IN REMOTE AREAS.

SYNCROMIC SURVEILLANCE TO ADDRESSING EMERGING BIOTHREATS

IMPACT OF IL-15 IMMUNOTHERAPY ON TISSUE-SPECIFIC CD8 T CELLS TO REDUCE THE CNS HIV RESERVOIR SEEDING AND PERSISTENCE - PROJECT SUMMARY HIV PERSISTS LONG-TERM IN THE CENTRAL NERVOUS SYSTEM (CNS) EVEN IN THE PRESENCE OF ANTIRETROVIRAL THERAPY (ART). ONE STRATEGY TO TARGET HIV RESERVOIRS IN THE CNS IS TO DEVELOP INTERVENTIONS AIMED AT ENHANCING THE BREADTH AND MAGNITUDE OF CD8 T CELLS, WHICH CAN PENETRATE AND PERSIST IN THE BRAIN AS TISSUE RESIDENT CELLS. OUR GROUP HAS SHOWN THAT HIV-SPECIFIC CD8 T CELLS CAN LIMIT HIV RESERVOIR SEEDING IN ACUTE INFECTION IN THE PERIPHERY WHEN ART IS INITIATED DURING ACUTE INFECTION. WE HAVE DEVELOPED UNIQUE TOOLS TO ANALYZE THESE CELLS IN THE CEREBROSPINAL FLUID (CSF) AND SHOWED THAT HIV-SPECIFIC CD8 T CELLS CAN ALSO BE DETECTED IN THE CSF DURING ACUTE HIV INFECTION AND PERSIST IN THE CSF FOR UP TO 2 YEARS AFTER ART INITIATION. IMPORTANTLY, THE PRESENCE OF THESE HIV-SPECIFIC CD8 T CELLS IS BENEFICIAL FOR LIMITING NEUROINFLAMMATION BUT NOT ENOUGH TO FULLY ELIMINATE HIV RESERVOIRS IN THE CNS. THE GOAL OF THIS PROJECT IS TO TEST WHETHER THE IMMUNOMODULATION OF INNATE-LIKE AND ADAPTIVE CD8 T CELLS VIA A NOVEL IL-15 SUPER-AGONIST (N-803) CAN SIGNIFICANTLY REDUCE HIV CNS RESERVOIRS WITHOUT CAUSING NEUROTOXICITY. INDEED, IL-15 PROMOTES STRONG ACTIVATION AND EXPANSION OF HIV-SPECIFIC CD8 T CELLS AND IMPROVES THEIR ABILITY TO KILL REACTIVATED HIV RESERVOIR CELLS IN VITRO. IL-15 ENHANCES MEMORY CD8 T CELL GENERATION AND PERSISTENCE IN TISSUES AS WELL AS TRAFFICKING TO THE CNS. IL-15 CAN ALSO PROMOTE THE CONVERSION OF CD8 T CELLS INTO ANTIGEN- INDEPENDENT INNATE-LIKE EFFECTOR CELLS, AS WELL AS THE ACTIVATION AND EXPANSION OF NK CELLS. IN NONHUMAN PRIMATES (NHP), IL-15 ENHANCED THE FUNCTION OF SIV-SPECIFIC CD8 T CELL RESPONSES RESULTING IN REDUCED PLASMA VIRAL LOADS AND INCREASED THE MIGRATION OF SIV-SPECIFIC CD8 T CELLS TO B CELL FOLLICLES. THESE RESULTS HAVE SUPPORTED THE EVALUATION OF IL-15 IMMUNOMODULATORY POTENTIAL IN HIV REMISSION STRATEGIES. HOWEVER, THE POTENTIAL FOR IL-15 IMMUNOTHERAPY TO REDUCE HIV PERSISTENCE IN THE CNS REMAINS UNKNOWN. IN THIS PROJECT, WE WILL STUDY THE IMPACT OF IL-15 ON INNATE-LIKE AND ADAPTIVE CD8 T CELLS IN TWO HUMAN HIV REMISSION CLINICAL TRIALS IN WHICH PARTICIPANTS RECEIVE N-803: THE RV550 TRIAL IN BANGKOK, THAILAND, ADMINISTERING 3 DOSES OF N-803 AT TIME OF ART INITIATION DURING ACUTE HIV INFECTION, AND THE ACTG A5386 TRIAL ADMINISTERING 8 DOSES OF N-803 IN PEOPLE WITH HIV ON ART AND UNDERGOING AN ANALYTIC TREATMENT INTERRUPTION. WE WILL ALSO CONDUCT TWO NHP EXPERIMENTS FOLLOWING THE DESIGN OF THE TWO HUMAN TRIALS, THAT WILL PROVIDE US WITH ACCESS TO BRAIN TISSUE AT NECROPSY. COLLECTIVELY, THESE STUDIES WE ALLOW US TO DETERMINE WHETHER N-803 ADMINISTRATION IN ACUTE INFECTION IS SAFE FOR THE CNS AND CAN ENHANCE HIV-SPECIFIC CD8 T CELL-MEDIATED REDUCTION OF THE CNS RESERVOIRS. WE WILL ALSO DETERMINE WHETHER REPEATED DOSING OF N-803 GIVEN DURING ART FACILITATES INNATE-LIKE CD8 T CELL-MEDIATED REDUCTION OF CNS HIV RESERVOIRS. THESE RESULTS SHOULD HELP DEFINE MECHANISMS BY WHICH CD8 T CELLS CAN CLEAR HIV RESERVOIRS FROM THE CNS AS WELL AS CNS SAFETY DURING AN IMMUNOMODULATORY INTERVENTION THAT MAY ULTIMATELY INFORM ON THE DEVELOPMENT OF THERAPEUTIC STRATEGIES TO ERADICATE THE HIV RESERVOIRS FROM THE CNS. 1

EVALUATION OF NEUROPHYSIOLOGIC AND SYSTEMATIC CHANGES DURING AEROMEDICAL EVACUATION AND EN ROUTE CARE OF COMBAT CASUALTIES IN A SWINE POLYTRAUMA

GLOBAL HEALTH ENGAGEMENT TRAINING, ENGAGEMENTS, AND CROSS-CUTTING FUNCTIONS

TRIPLEDX CLINICAL DECISION SUPPORT TOOL

CLINICAL SKILLS ASSESSMENT OF MEDICAL PROVIDERS (CSAMP)

DEVELOPMENT AND VALIDATION OF THE DRAG HUMANIZED MOUSE MODEL FOR DENGUE VIRUS INFECTION AND VACCINE EVALUATION

MONOAMINERGIC NEUROTRANSMITTER IMPAIRMENT FROM TRAUMATIC BRAIN INJURY (TBI) AS AN EARLY MECHANISM IN NEURODEGENERATIVE DISEASE

SUBUNIT VACCINES AGAINST CAOMPLOBACTER JEUNI AND ENTEROTOXIGENIC ESCHERICHIA COLI (ETEC)

HEALTH SERVICES RESEARCH PROGRAM (HSRP)

UNDERSTANDING PANDEMIC EVOLUTION THROUGH NETWORKED DATA (UPEND) - PROJECT SUMMARY/ABSTRACT THERE ARE NEARLY 38 MILLION PEOPLE LIVING WITH HIV (PLWH) WORLDWIDE WHO MAY BE VULNERABLE TO POOR NEUROBEHAVIORAL AND HIV-RELATED OUTCOMES FROM CORONAVIRUS DISEASE 2019 (COVID-19), CAUSED BY SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2). OUR OVERARCHING GOAL IS TO IMPROVE MENTAL HEALTH AND OTHER CLINICAL OUTCOMES FOR PLWH DURING THE COVID-19 PANDEMIC. THE OBJECTIVE OF THE PROPOSED RESEARCH IS TO EXPLAIN HOW COVID- 19 CONTRIBUTES TO ADVERSE NEUROBEHAVIORAL AND HIV-RELATED OUTCOMES IN PLWH AND TO MEASURE THE EFFECTIVENESS OF VACCINATION AS A BIOLOGIC TOOL TO MITIGATE COVID-19-ASSOCIATED NEUROCOGNITIVE IMPAIRMENT. THIS WILL HELP US TO IMPROVE CLINICAL OUTCOMES DURING THIS PANDEMIC AND INFORM STRATEGIES TO BETTER PREPARE FOR FUTURE DISEASE OUTBREAKS. WE WILL LEVERAGE FOUR HIV-FOCUSED COHORT STUDIES SPANNING THE UNITED STATES, THAILAND, KENYA, UGANDA, TANZANIA, AND NIGERIA WITH APPROXIMATELY 6800 PARTICIPANTS BEFORE THE PANDEMIC AND ONGOING FOLLOW-UP OF AN ADDITIONAL 1000 PARTICIPANTS IN THE COVID-19 ERA. AIDED BY SIMILARITIES ACROSS PROTOCOLS, DEIDENTIFIED DATA AND SPECIMENS WILL BE USED TO ACHIEVE THE FOLLOWING SPECIFIC AIMS: (1) IDENTIFY PREDICTORS OF COVID-19 VACCINE UPTAKE AND RESPONSIVENESS IN PEOPLE WITH AND WITHOUT HIV; (2) IDENTIFY CLUSTERS OF DETERMINANTS THAT IMPACTED VIRAL SUPPRESSION AND NEUROBEHAVIORAL HEALTH (DEPRESSION AND COGNITION) AMONG PEOPLE WITH HIV DURING THE COVID-19 PANDEMIC; AND (3) DETERMINE LONG TERM IMPLICATIONS OF COVID-19 ON NEUROCOGNITION AND MORTALITY AND THE IMPACT OF VACCINATION IN MITIGATING THESE EFFECTS IN PEOPLE WITH AND WITHOUT HIV. DATA WILL UNDERGO EXTENSIVE PREPARATION AND HARMONIZATION TO ENABLE THE USE OF ADVANCED STATISTICAL METHODS, INCLUDING MACHINE-LEARNING APPROACHES, TO BETTER UNDERSTAND THE COMPLEX FACTORS CONTRIBUTING TO EACH OUTCOME OF INTEREST, INCLUDING BIOLOGIC, SOCIAL, BEHAVIORAL, AND REGIONAL FACTORS. WE WILL SYSTEMATICALLY CAPTURE AVAILABILITY AND RECEIPT OF COVID-19 VACCINATIONS; IDENTIFY FACTORS ASSOCIATED WITH VACCINE UPTAKE; USE A CENTRALIZED LABORATORY TO MONITOR FOR INCIDENT INFECTIONS (INCLUDING BREAKTHROUGH) AND IMMUNE RESPONSES TO VACCINATION; AND PROSPECTIVELY SURVEY PARTICIPANTS ABOUT KNOWLEDGE, ATTITUDES, AND PRACTICES RELATED TO VACCINATION TO BETTER DEFINE SPECIFIC BARRIERS. THROUGHOUT THE CONSTANTLY EVOLVING COVID-19 PANDEMIC, WE WILL EVALUATE CHANGES IN NEUROCOGNITIVE HEALTH, HIV VIRAL LOAD, AND CD4 COUNT. PARTICIPANTS WITH AND WITHOUT A HISTORY OF COVID-19, WITH AND WITHOUT COVID-19 VACCINATION, AND WITH AND WITHOUT HIV WILL BE MONITORED FOR THE DEVELOPMENT OR PROGRESSION OF NONINFECTIOUS COMORBID CONDITIONS WITH A FOCUS ON MENTAL HEALTH AND NEUROCOGNITIVE IMPAIRMENT FOR UP TO THREE YEARS AFTER INFECTION. THIS RESEARCH WILL ENABLE US TO DRAW GLOBALLY-RELEVANT CONCLUSIONS ABOUT THE IMPACT OF COVID-19 ON HIV CARE ENGAGEMENT AND OUTCOMES, EXTRACT LESSONS FOR PUBLIC HEALTH RESPONSES TO COVID-19 AND FUTURE PANDEMICS, AND EVALUATE THE EFFECTS OF HIV STATUS AND VACCINATION ON SARS-COV-2 OUTCOMES.

DEVELOPMENT OF PREDICTIVE ALGORITHMS FOR PATIENT BLEEDING OR CLOTTING DURING EXTRACORPOREAL MEMBRANE OXYGEN SUPPORT

PREVENTION, INTERVENTION, AND POSTVENTION PROGRAMS TO ADVANCE THE U.S. DEFENSE SUICIDE PREVENTION STRATEGY

PREVENTION, INTERVENTION, AND POSTVENTION PROGRAMS TO ADVANCE THE U.S. DEFENSE SUICIDE PREVENTION STRATEGY

GLOBAL HEALTH ENGAGEMENT RESEARCH AND SCHOLARSHIP

NATIONAL CENTER FOR DISASTER MEDICINE AND PUBLIC HEALTH (NCDMPH)/NATIONAL DISASTER MEDICAL SYSTEM (NDMS) PILOT FY 21 (PHASE II)

INTRAMURAL RESEARCH PROGRAM

HEALTH SERVICES RESEARCH PROGRAM

PORTABLE HEMODIALYSIS FACILITATING HOME USE AND FIELD IMPLEMENTATION

ELECTRICAL STIMULATION OF OSSEOINTEGRATED PROSTHETIC LIMBS FOR INFECTION CONTROL AND ENHANCED TISSUE INTEGRATION

DEFENSE&VETERANS CENTER FOR INTEGRATIVE PAIN MANAGEMENT (DVCIPM) CORE PROGRAM

THE COMBAT AND TRAINING QUERYABLE BLAST EXPOSURE REPOSITORY (CONQUER)

'IMPROVING PUBLIC HEALTH SURVEILLANCE AND OUTBREAK PREPAREDNESS BY OPTIMIZING INFECTIOUS DISEASE DETECTION IN THE USAF'

SAFETY INFORMATION FOR DIETARY SUPPLEMENTS

INVESTIGATING TRAINING ASSOCIATED BLAST PATHOLOGY (INVICTA)

CENTER FOR INTEGRATIVE PAIN MANAGEMENT

CARDIOVASCULAR CONSEQUENCES OF TRAUMATIC BRAIN INJURY

DEFENSE & VETERANS CENTER FOR INTEGRATIVE PAIN MANAGEMENT (DVCIPM) - CORE PROGRAM 2

ENCOUNTER SKILLS TRAINING ASYNCHRONOUS DEVELOPMENT, TRAIN THE TRAINER, AND TRAINING IMPLEMENTATION SUPPORT

TOTAL FORCE SUICIDE DEATH REVIEWS TO ADVANCE THE DEPARTMENT OF AIR FORCE SUICIDE PREVENTION PROGRAM PRIORITIES

DESIGNING HIV-1 ENVELOPE IMMUNOGENS TO MAXIMIZE NEUTRALIZATION BREADTH THROUGH USE OF MULTIPLE FOUNDER ENVELOPE ANTIGENS - PROJECT SUMMARY/ABSTRACT AN HIV-1 (HIV) VACCINE CAPABLE OF ELICITING BROAD AND POTENT NEUTRALIZING ANTIBODY (AB) RESPONSE TO HIV ENVELOPE (ENV) REMAINS ELUSIVE. HIV HAS A HIGH MUTATION RATE, ENV IS HIGHLY GLYCOSYLATED AS WELL AS CONFORMATIONALLY DYNAMIC AND, WELL-CHARACTERIZED BROADLY NEUTRALIZING RESPONSES REPORTED TO DATE HAVE BEEN GENERATED AFTER CHRONIC HIV INFECTION, RATHER THAN BY CANDIDATE HIV VACCINES. RECENTLY, WE REPORTED THAT PRECURSOR BROADLY NEUTRALIZING ANTIBODIES (BNABS) CAN DEVELOP DURING EARLY HIV INFECTION AND NEUTRALIZATION BREADTH WAS MORE FREQUENT WHEN MULTIPLE HIV VARIANTS ESTABLISHED INFECTION IN AN INDIVIDUAL, DEFINED HERE AS MULTIPLE-FOUNDER VARIANT (MFV) INFECTION. FURTHERMORE, ENV DIVERSITY DURING INITIAL INFECTION WAS HIGHER IN INDIVIDUALS WHO DEVELOPED NEUTRALIZATION BREADTH. WE CONCLUDED THAT ENV-SPECIFIC B CELL DEVELOPMENT WITHIN ONE MONTH OF INITIAL HIV INFECTION CAN PREDICT NEUTRALIZATION BREADTH YEARS LATER; THIS PHENOMENON HIGHLIGHTS THE CRITICAL IMPORTANCE OF THESE INITIAL INTERACTIONS, WHICH PRIME B CELLS AT THE EARLIEST STAGES OF HIV INFECTION. TO DETERMINE THE IMMUNOGENICITY OF AN HIV VACCINE DESIGN BASED ON THE MFV CONCEPT, WE FORMULATED A COCKTAIL OF FIVE ENV TRIMER PROTEINS DERIVED FROM MFV IN ACUTE INFECTION. THE ENV SEQUENCES CORRESPONDED TO 5 FOUNDER LINEAGES IN ONE PARTICIPANT. THEY WERE FURTHER OPTIMIZED BY STABILIZING THEM IN A CLOSED CONFORMATION USING THE ’REPAIR AND STABILIZE’ STRATEGY DEVELOPED BY JANSSEN PHARMACEUTICALS. THE COCKTAIL OF MINIMALLY DISTANT, STABILIZED ENV PROTEINS WERE FORMULATED WITH THE NOVEL VACCINE ADJUVANT, ARMY LIPOSOME FORMULATION PLUS QS-21 (ALFQ). PRELIMINARY IMMUNOGENICITY DATA IN RABBITS DEMONSTRATED THAT THIS VACCINE CANDIDATE ELICITED A GREATER BREADTH OF NEUTRALIZING AB RESPONSES THAN AN EQUIVALENT TOTAL DOSE OF A SINGLE STABILIZED ENV TRIMER PROTEIN. THESE MINIMALLY DISTANT IMMUNOGENS ALSO ELICITED A HIGHER MAGNITUDE OF IGM RESPONSES TO HIV; A PREDICTOR OF SUBSEQUENT NEUTRALIZATION BREADTH IN OUR STUDIES OF EARLY INFECTION. THEREFORE, WE PROPOSE TO SELECT AN OPTIMAL COMBINATION OF MINIMALLY DISTANT HIV ENV IMMUNOGENS THAT MIMIC THE DIVERSITY AND DEVELOPMENT OF NEUTRALIZING AB BREADTH SEEN IN ACUTE INFECTIONS WITH MFV IN VITRO AND IN VIVO. WE WILL OPTIMIZE THE ANTIGENICITY OF THE HIV ENV TRIMER IMMUNOGENS BY COMPARING NATIVE STABILIZED TRIMERS WITH ENV TRIMERS THAT HAVE SHORTENED HYPERVARIABLE (HV) LOOPS AND GLYCAN MODIFICATIONS IN AN ATTEMPT TO IMPROVE THEIR ANTIGENICITY (AIM 1). WE WILL OPTIMIZE IMMUNOGEN DELIVERY AND DISPLAY STRATEGIES, INCLUDING MULTIVALENT TRIMERIC ENVS DELIVERED AS MESSENGER RNA (MRNA) AND, MULTIVALENT IMMUNOGEN DISPLAY ON SELF-ASSEMBLING LIPOSOMAL COBALT PORPHYRIN PHOSPHOLIPOSOMES (COPOP) THAT AFFORD ENV BASE SHIELDING (AIM 2). WE WILL UTILIZE PRE-SPECIFIED GO/NO-GO CRITERIA TO DOWNSELECT THE OPTIMAL VACCINE REGIMEN OF OPTIMIZED MINIMALLY DISTANT HIV VACCINE CANDIDATES, TO EVALUATE PROTECTIVE IMMUNE RESPONSES IN NON-HUMAN PRIMATE SHIV CHALLENGE STUDIES (AIM 3). OUR LONG-TERM GOAL IS TO DEVELOP A MULTIVALENT HIV VACCINE CANDIDATE THAT ELICITS PROTECTIVE BROADLY NEUTRALIZING AB RESPONSES FOR SUBSEQUENT MANUFACTURE AND EVALUATION IN HUMAN CLINICAL TRIALS.

ANAPLASMA REGULATION OF HOST GRANULOCYTE FUNCTIONS

DEFENSE AND VETERANS CENTER FOR INTEGRATIVE PAIN MANAGEMENT (DVCIPM) RESEARCH AND CONSULTATION PROJECTS - CORE PROGRAM 2