{"success":true,"result":{"grants":[{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"BAYLOR COLLEGE OF MEDICINE","value":8342191,"savings":2140739,"link":null,"description":"ABSTRACT This supplement request is for a Phase 3, randomized, observer-blind, placebo-controlled study to evaluate the efficacy, safety and immunogenicity, of a SARS-CoV-2 recombinant spoke protein nanoparticle vaccine (SARS-CoV-2 rS) with Matric-M1TM adjuvant in adult participants over 18 years of age who have no known history of SARS-CoV-2 infection but whose locations or circumstances put them at appreciable risk of acquiring COVID-19 and/or SARS-CoV-2 infection. This request also relates to other COVID 19 activities."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON","value":34703331,"savings":5636408,"link":null,"description":"Project summary / ABSTRACT The mission of the ITN is to advance the clinical application of immune tolerance by performing high quality clinical trials of emerging therapeutics based upon testable mechanistic hypotheses. The ITN is structured in order to interrogate different diseases across the immunologic spectrum, with integration of innovative clinical studies and cutting edge immunology laboratory analysis. The ITN approach—clinical assessment of novel tolerance therapeutics, while we simultaneously evaluate the cellular, genetic, and immunologic mechanisms of disease and how they are altered in response to therapy—creates a framework for advancing cross-disease and cross-discipline knowledge, all designed to accelerate therapeutic options for major diseases. In this renewal application, we describe the scientific and operational framework that will enable the ITN to successfully enhance the development of tolerance therapies in transplantation, autoimmunity, and allergy. We outline a process to evolve our current strategies into the next generation of planned trials, as well as how we plan to operate a nimble, future-focused organization, poised to lead and adopt innovations that are currently unknown. We propose a collaborative structure involving hundreds of investigators, advisors, and clinical sites working in tandem with a core group of ITN staff, operating a program that is both scientifically and financially efficient. Several new innovations recently adopted by the ITN will encourage widespread involvement from academic investigators, including expanded resource sharing and data sharing operations. With lead institutional commitment from the Benaroya Research Institute and the University of California San Francisco, and participation of more than 20 other major institutions represented in leadership and major advisory roles, the ITN strives to continue to successfully pioneer high impact clinical trials and mechanistic studies in areas of unmet medical need."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"BRIGHAM & WOMEN`S HOSPITAL","value":7828320,"savings":7428486,"link":null,"description":"DISCOVERING DURABLE PAN-CORONAVIRUS IMMUNITY - OVERALL SUMMARY SEVERE ACUTE RESPIRATORY SYNDROME (SARS) CORONAVIRUS (COV)-2 IS A DEVASTATING HUMAN THREAT. WHILE SUCCESSFUL VACCINE PROGRAMS ARE UNDERWAY, GENETIC DRIFT AND IMMUNE ESCAPE HAVE ALREADY BEGUN TO SUBVERT IMMUNITY, WITH MORE VARIANTS LIKELY TO CONTINUE TO EMERGE. MOREOVER, THE RATES OF ZOONOTIC COV TRANSMISSION HAVE INCREASED OVER THE PAST TWO DECADES—INDICATING THAT IT MAY NOT BE LONG BEFORE ANOTHER COV BREACHES HOST-SPECIES BARRIERS INTO HUMANS. NEXT GENERATION VACCINE DESIGN STRATEGIES THAT ARE ABLE TO PROVIDE ROBUST PROTECTION AGAINST EVOLVING SARS-COV-2 STRAINS IN ADDITION TO OTHER COVS ARE URGENTLY NEEDED. THE OVERALL GOAL OF THIS PROGRAM IS TO PRODUCE CRITICAL INFORMATION NECESSARY FOR THE DESIGN AND TESTING OF NEXT GENERATION VACCINE STRATEGIES THAT PROVIDE PROTECTIVE EFFICACY WITH THE GREATEST POSSIBLE BREADTH ACROSS THE COV FAMILY. THE OVERALL PROGRAM HYPOTHESIS IS THAT IMMUNOLOGICAL DISCERNMENT OF HETEROGENEITY IN HUMAN RESPONSES TO SARS-COV-2 INFECTION AND VACCINATION WILL ILLUMINATE FACTORS THAT CAN IMPACT EFFICACY AND BREADTH OF COV VACCINE STRATEGIES. THIS HYPOTHESIS IS SUPPORTED BY RECENT PUBLICATIONS AND PRELIMINARY DATA FROM OUR TEAM. IN THIS REGARD, ALTHOUGH HUNDREDS OF VACCINES ARE UNDER DEVELOPMENT, THE TARGETS MOST RELEVANT FOR PAN- COV IMMUNITY MAY DEFY THE SIMPLE NEED FOR THE INDUCTION OF NEUTRALIZING ANTIBODY RESPONSES, WHICH LARGELY BIND TO NON-CONSERVED AREAS IN THE S1 REGION OF THE VIRAL SPIKE (S) PROTEIN—SUSCEPTIBLE TO VIRAL ESCAPE. EMERGING EVIDENCE FROM OUR TEAM POINTS TO THE IMPORTANCE OF THE S2 REGION, WHICH IS MORE CONSERVED ACROSS COVS. OUR TEAM HAS FOUND THAT RAPID INDUCTION OF ANTI-S2 ANTIBODIES IS CONNECTED TO LESS DEATH IN SEVERE DISEASE, MORE CROSS-REACTIVE MEMORY B CELL RESPONSES, SWIFT HEALING IN MILD DISEASE, AND IMPROVED ANTIBODY DURABILITY AFTER DISEASE RESOLUTION. THE FACTORS UNDERLYING WHY SOME PEOPLE DEVELOP BETTER-CLINICAL-OUTCOME- ASSOCIATED CROSSREACTIVE ANTI-S2 IMMUNE RESPONSES REMAINS TO BE FULLY DEFINED. WE HAVE ASSEMBLED A MULTIDISCIPLINARY TEAM WITH EXPERTISE IN IMMUNOLOGY, VIROLOGY, GENETICS, MEDICINE, BIOCHEMISTRY, STRUCTURAL BIOLOGY AND MATHEMATICS TO ACHIEVE THE OVERALL PROGRAM GOAL. THE COMPLEMENTARY AND INTEGRATIVE EXPERTISE OF THE TEAM WILL COME TOGETHER TO: 1) FINELY MAP THE HUMORAL AND CELLULAR RESPONSES TO SARS-COV-2 VARIANTS AND CORONAVIRAL RELATIVES THAT EMERGE AFTER NATURAL INFECTION OR VACCINATION, 2) DEFINE THE MECHANISM(S) BY WHICH THESE RESPONSES CONFER PROTECTION, AND 3) UTILIZE THESE MECHANISTIC CORRELATES OF IMMUNITY TO INSPIRE CUTTING EDGE, STRUCTURALLY STABLE NATIVE-LIKE S ANTIGENS THAT WILL BE USED IN A STEP-WISE IMPROVEMENT APPROACH IN VACCINATION AND PROTECTION STUDIES. COLLECTIVELY, THE DATA GENERATED BY THIS TEAM WILL (A) IDENTIFY IMMUNOLOGICAL CORRELATES OF ANTI-COV BREADTH EXPECTED TO INFORM VACCINE DESIGN; (B) DEFINE THE MOST CONSERVED TARGETS ON COV S ACCESSIBLE TO THE HUMAN ADAPTIVE IMMUNE SYSTEM AND MECHANISTIC INSIGHTS INTO THEIR RECOGNITION; (C) GENERATE NOVEL IMMUNOGENS INCORPORATING B AND T CELL STRATEGIES INFORMED BY (A-C) ABOVE; AND (D) TEST THEM IN THE CONTEXT OF PROGRAM-OPTIMIZED DELIVERY METHODS TO MAXIMIZE BREADTH OF PROTECTIVE, DURABLE COV IMMUNITY."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"BRIGHAM & WOMEN`S HOSPITAL","value":11809995,"savings":407461,"link":null,"description":"DISCOVERING DURABLE PAN-CORONAVIRUS IMMUNITY - OVERALL SUMMARY SEVERE ACUTE RESPIRATORY SYNDROME (SARS) CORONAVIRUS (COV)-2 IS A DEVASTATING HUMAN THREAT. WHILE SUCCESSFUL VACCINE PROGRAMS ARE UNDERWAY, GENETIC DRIFT AND IMMUNE ESCAPE HAVE ALREADY BEGUN TO SUBVERT IMMUNITY, WITH MORE VARIANTS LIKELY TO CONTINUE TO EMERGE. MOREOVER, THE RATES OF ZOONOTIC COV TRANSMISSION HAVE INCREASED OVER THE PAST TWO DECADES—INDICATING THAT IT MAY NOT BE LONG BEFORE ANOTHER COV BREACHES HOST-SPECIES BARRIERS INTO HUMANS. NEXT GENERATION VACCINE DESIGN STRATEGIES THAT ARE ABLE TO PROVIDE ROBUST PROTECTION AGAINST EVOLVING SARS-COV-2 STRAINS IN ADDITION TO OTHER COVS ARE URGENTLY NEEDED. THE OVERALL GOAL OF THIS PROGRAM IS TO PRODUCE CRITICAL INFORMATION NECESSARY FOR THE DESIGN AND TESTING OF NEXT GENERATION VACCINE STRATEGIES THAT PROVIDE PROTECTIVE EFFICACY WITH THE GREATEST POSSIBLE BREADTH ACROSS THE COV FAMILY. THE OVERALL PROGRAM HYPOTHESIS IS THAT IMMUNOLOGICAL DISCERNMENT OF HETEROGENEITY IN HUMAN RESPONSES TO SARS-COV-2 INFECTION AND VACCINATION WILL ILLUMINATE FACTORS THAT CAN IMPACT EFFICACY AND BREADTH OF COV VACCINE STRATEGIES. THIS HYPOTHESIS IS SUPPORTED BY RECENT PUBLICATIONS AND PRELIMINARY DATA FROM OUR TEAM. IN THIS REGARD, ALTHOUGH HUNDREDS OF VACCINES ARE UNDER DEVELOPMENT, THE TARGETS MOST RELEVANT FOR PAN- COV IMMUNITY MAY DEFY THE SIMPLE NEED FOR THE INDUCTION OF NEUTRALIZING ANTIBODY RESPONSES, WHICH LARGELY BIND TO NON-CONSERVED AREAS IN THE S1 REGION OF THE VIRAL SPIKE (S) PROTEIN—SUSCEPTIBLE TO VIRAL ESCAPE. EMERGING EVIDENCE FROM OUR TEAM POINTS TO THE IMPORTANCE OF THE S2 REGION, WHICH IS MORE CONSERVED ACROSS COVS. OUR TEAM HAS FOUND THAT RAPID INDUCTION OF ANTI-S2 ANTIBODIES IS CONNECTED TO LESS DEATH IN SEVERE DISEASE, MORE CROSS-REACTIVE MEMORY B CELL RESPONSES, SWIFT HEALING IN MILD DISEASE, AND IMPROVED ANTIBODY DURABILITY AFTER DISEASE RESOLUTION. THE FACTORS UNDERLYING WHY SOME PEOPLE DEVELOP BETTER-CLINICAL-OUTCOME- ASSOCIATED CROSSREACTIVE ANTI-S2 IMMUNE RESPONSES REMAINS TO BE FULLY DEFINED. WE HAVE ASSEMBLED A MULTIDISCIPLINARY TEAM WITH EXPERTISE IN IMMUNOLOGY, VIROLOGY, GENETICS, MEDICINE, BIOCHEMISTRY, STRUCTURAL BIOLOGY AND MATHEMATICS TO ACHIEVE THE OVERALL PROGRAM GOAL. THE COMPLEMENTARY AND INTEGRATIVE EXPERTISE OF THE TEAM WILL COME TOGETHER TO: 1) FINELY MAP THE HUMORAL AND CELLULAR RESPONSES TO SARS-COV-2 VARIANTS AND CORONAVIRAL RELATIVES THAT EMERGE AFTER NATURAL INFECTION OR VACCINATION, 2) DEFINE THE MECHANISM(S) BY WHICH THESE RESPONSES CONFER PROTECTION, AND 3) UTILIZE THESE MECHANISTIC CORRELATES OF IMMUNITY TO INSPIRE CUTTING EDGE, STRUCTURALLY STABLE NATIVE-LIKE S ANTIGENS THAT WILL BE USED IN A STEP-WISE IMPROVEMENT APPROACH IN VACCINATION AND PROTECTION STUDIES. COLLECTIVELY, THE DATA GENERATED BY THIS TEAM WILL (A) IDENTIFY IMMUNOLOGICAL CORRELATES OF ANTI-COV BREADTH EXPECTED TO INFORM VACCINE DESIGN; (B) DEFINE THE MOST CONSERVED TARGETS ON COV S ACCESSIBLE TO THE HUMAN ADAPTIVE IMMUNE SYSTEM AND MECHANISTIC INSIGHTS INTO THEIR RECOGNITION; (C) GENERATE NOVEL IMMUNOGENS INCORPORATING B AND T CELL STRATEGIES INFORMED BY (A-C) ABOVE; AND (D) TEST THEM IN THE CONTEXT OF PROGRAM-OPTIMIZED DELIVERY METHODS TO MAXIMIZE BREADTH OF PROTECTIVE, DURABLE COV IMMUNITY."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"Duke University","value":115543799,"savings":26084566,"link":null,"description":"CENTER FOR INNOVATIVE TRIALS IN CHILDREN AND ADULTS (TRIDENT)"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"Duke University","value":21469057,"savings":12609225,"link":null,"description":"CENTER FOR INNOVATIVE TRIALS IN CHILDREN AND ADULTS (TRIDENT)"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"Duke University","value":10478045,"savings":6906037,"link":null,"description":"DESIGN AND DEVELOPMENT OF A PAN-BETACORONAVIRUS VACCINE - ABSTRACT - OVERALL COMPARED TO SARS-COV-1 AND MERS, THE CURRENT SARS-COV-2 VIRUS IS HIGHLY TRANSMISSIBLE AND TO DATE HAS CAUSED OVER 85,000,000CASES WORLDWIDEWITH OVER 1,800,000 DEATHS. WITH AN ENDEMIC POPULATION OF MULTIPLEOTHER STRAINS OF COVS IN BATS, RODENTS WITH INTERMEDIATE HOSTS, CIVETS AND PANGOLINS, AND BECAUSE OF THE ABILITY OF COVS TO RECOMBINE, IT IS A CERTAINTY THAT NEW COVS WITH INFECTIOUS POTENTIAL FOR HUMANS WILL CAUSE FUTURE HUMAN PANDEMICS. TO ADDRESS THIS PROBLEM IN A FOCUSED AND INTEGRATED WAY, THIS P01 TEAM OF VIROLOGISTS, IMMUNOLOGISTS, COMPUTATIONAL BIOLOGISTS, STRUCTURAL BIOLOGISTS, BIOPHYSICISTS, EVOLUTIONARY BIOLOGISTS, AND TRADITIONAL VACCI NOLOGISTS WILL DEVELOP PANBETACORONAVIRUS (PANBETACOV) VACCINES, INCLUDING MERBECOVIRUSES (GROUP 2C), WHICH GAVE RISE TO MERS, AND SARBECOVIRUSES (GROUP 2B), WHICH GAVE RISE TO SARS COV-1 AND SARS COV-2, THE THREE MOST DEADLY BETACOV HUMAN OUTBREAKS. THE SIGNIFICANCE OF THIS GRANT IS THAT IT WILL PROVIDE FOR PANBETACOV VACCINES FOR FUTURE EPIDEMICS THAT CAN BE IMMEDIATELY AVAILABLE AT THE ONSET OF A BETACOV PANDEMIC, AVOIDING MUCH OF THE HUMAN TRAGEDY AND SOCIAL DISRUPTION CAUSED BY A PANDEMIC. THE OVERALL SPECIFIC AIMS OF THE P01 ARE: AIM 1. DEVELOP AND CHARACTERIZE IMMUNOGENICITY OF PANBETACOV SARBECOVIRUS (GROUP 2B) VACCINE CANDIDATES. AIM 2. DETERMINE GROUP 2B VACCINE CANDIDATE PROTECTION CAPACITY AGAINST GROUP 2B PANEL OF VIRUSES. AIM 3. DEVELOP PANBETACOVMERBECOVIRUS (GROUP2C) VACCINE CANDIDATES, DETERMINETHEIR IMMUNOGENICITY, CROSS- REACTIVITY WITH OTHER BETACOVS AND PROTECTION CAPACITY AGAINST GROUP 2C PANEL OF VIRUSES. THIS PROGRAM PROJECT GRANT INCLUDES FOUR PROJECTS. PROJECT 1 WILL DESIGN VACCINES IN ALPHAVIRUS REPLICON PARTICLE (VRP) VACCINE SYSTEM, DEVELOP AND TEST P01 VACCINES IN THEIR UNIQUE MOUSE COV CHALLENGE MODELS. PROJECT 2 WILL USE STRUCTURE-BASED MOLECULAR MODELING AND MONOMER AND MULTIMER NANOPARTICLE SPIKE PROTEIN DESIGNS AND TEST IN WILD-TYPE MOUSE MODELS. PROJECT 3 WILL BOTH DESIGN COV VACCINES AND TEST VACCINE DESIGNS EXPRESSED AS MRNAS IN LIQUID NANOPARTICLES (LNPS). PROJECT 4 WILL COMPUTATIONALLY DESIGN B AND T CELL PANBETACOV VACCINES. THIS P01 PROPOSES THREE CORES: AN ADMINISTRATIVE CORE, A BIOCONTAINMENT AND IMMUNE MONITORING CORE, AND A NON-HUMAN PRIMATE CORE. WORK IN THIS P01 WILL PROVIDE PANBETACOV VACCINES TO PROTECT AGAINST ESCAPE MUTANTS OF SARS-COV-2 IN THE CURRENT EPIDEMIC, AND WILL BE AVAILABLE TO PROTECT SOCIETY AGAINST NEW BETACOVS THAT MIGHT EMERGE TO INFECT HUMANS IN THE FUTURE."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"Duke University","value":17521953,"savings":610668,"link":null,"description":"DESIGN AND DEVELOPMENT OF A PAN-BETACORONAVIRUS VACCINE - ABSTRACT - OVERALL COMPARED TO SARS-COV-1 AND MERS, THE CURRENT SARS-COV-2 VIRUS IS HIGHLY TRANSMISSIBLE AND TO DATE HAS CAUSED OVER 85,000,000CASES WORLDWIDEWITH OVER 1,800,000 DEATHS. WITH AN ENDEMIC POPULATION OF MULTIPLEOTHER STRAINS OF COVS IN BATS, RODENTS WITH INTERMEDIATE HOSTS, CIVETS AND PANGOLINS, AND BECAUSE OF THE ABILITY OF COVS TO RECOMBINE, IT IS A CERTAINTY THAT NEW COVS WITH INFECTIOUS POTENTIAL FOR HUMANS WILL CAUSE FUTURE HUMAN PANDEMICS. TO ADDRESS THIS PROBLEM IN A FOCUSED AND INTEGRATED WAY, THIS P01 TEAM OF VIROLOGISTS, IMMUNOLOGISTS, COMPUTATIONAL BIOLOGISTS, STRUCTURAL BIOLOGISTS, BIOPHYSICISTS, EVOLUTIONARY BIOLOGISTS, AND TRADITIONAL VACCI NOLOGISTS WILL DEVELOP PANBETACORONAVIRUS (PANBETACOV) VACCINES, INCLUDING MERBECOVIRUSES (GROUP 2C), WHICH GAVE RISE TO MERS, AND SARBECOVIRUSES (GROUP 2B), WHICH GAVE RISE TO SARS COV-1 AND SARS COV-2, THE THREE MOST DEADLY BETACOV HUMAN OUTBREAKS. THE SIGNIFICANCE OF THIS GRANT IS THAT IT WILL PROVIDE FOR PANBETACOV VACCINES FOR FUTURE EPIDEMICS THAT CAN BE IMMEDIATELY AVAILABLE AT THE ONSET OF A BETACOV PANDEMIC, AVOIDING MUCH OF THE HUMAN TRAGEDY AND SOCIAL DISRUPTION CAUSED BY A PANDEMIC. THE OVERALL SPECIFIC AIMS OF THE P01 ARE: AIM 1. DEVELOP AND CHARACTERIZE IMMUNOGENICITY OF PANBETACOV SARBECOVIRUS (GROUP 2B) VACCINE CANDIDATES. AIM 2. DETERMINE GROUP 2B VACCINE CANDIDATE PROTECTION CAPACITY AGAINST GROUP 2B PANEL OF VIRUSES. AIM 3. DEVELOP PANBETACOVMERBECOVIRUS (GROUP2C) VACCINE CANDIDATES, DETERMINETHEIR IMMUNOGENICITY, CROSS- REACTIVITY WITH OTHER BETACOVS AND PROTECTION CAPACITY AGAINST GROUP 2C PANEL OF VIRUSES. THIS PROGRAM PROJECT GRANT INCLUDES FOUR PROJECTS. PROJECT 1 WILL DESIGN VACCINES IN ALPHAVIRUS REPLICON PARTICLE (VRP) VACCINE SYSTEM, DEVELOP AND TEST P01 VACCINES IN THEIR UNIQUE MOUSE COV CHALLENGE MODELS. PROJECT 2 WILL USE STRUCTURE-BASED MOLECULAR MODELING AND MONOMER AND MULTIMER NANOPARTICLE SPIKE PROTEIN DESIGNS AND TEST IN WILD-TYPE MOUSE MODELS. PROJECT 3 WILL BOTH DESIGN COV VACCINES AND TEST VACCINE DESIGNS EXPRESSED AS MRNAS IN LIQUID NANOPARTICLES (LNPS). PROJECT 4 WILL COMPUTATIONALLY DESIGN B AND T CELL PANBETACOV VACCINES. THIS P01 PROPOSES THREE CORES: AN ADMINISTRATIVE CORE, A BIOCONTAINMENT AND IMMUNE MONITORING CORE, AND A NON-HUMAN PRIMATE CORE. WORK IN THIS P01 WILL PROVIDE PANBETACOV VACCINES TO PROTECT AGAINST ESCAPE MUTANTS OF SARS-COV-2 IN THE CURRENT EPIDEMIC, AND WILL BE AVAILABLE TO PROTECT SOCIETY AGAINST NEW BETACOVS THAT MIGHT EMERGE TO INFECT HUMANS IN THE FUTURE."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"EMORY UNIVERSITY","value":51914880,"savings":18352822,"link":null,"description":"ANTIVIRAL COUNTERMEASURES DEVELOPMENT CENTER (AC/DC) - THE ANTIVIRAL COUNTERMEASURES DEVELOPMENT CENTER (AC/DC) WILL TARGET PATHOGENS IN FIVE FAMILIES OF RNA VIRUSES WITH SIGNIFICANT PANDEMIC POTENTIAL, WITH THE OVERARCHING GOAL TO IDENTIFY AND DEVELOP ORALLY BIOAVAILABLE, DIRECT ACTING ANTIVIRAL DRUGS (DAAS). SPECIFIC VIRAL TARGETS INCLUDE ZOONOTIC AND HUMAN VIRUSES IN THE CORONAVIRUS, PARAMYXOVIRUS, FLAVIVIRUS, PICORNAVIRUS, AND TOGAVIRUS FAMILIES. THE AC/DC MPIS DRS. PAINTER AND PLEMPER, WHO WILL LEAD THIS EFFORT, HAVE DEMONSTRATED THE POWER OF THEIR COMBINED EXPERTISE IN IDENTIFYING NOVEL ANTIVIRAL CHEMOTYPES AND ADVANCING THEM FROM HIT STAGE TO CLINICAL CANDIDATE, BEST EXEMPLIFIED BY THEIR SUCCESSFUL JOINT WORK ON MOLNUPIRAVIR, CONSIDERED FOR EMERGENCY APPROVAL AS THE FIRST ORAL THERAPEUTIC FOR THE TREATMENT OF COVID- 19. THE MPIS HAVE ASSEMBLED A TEAM OF RECOGNIZED EXPERTS IN THE BIOLOGY OF THE VIRAL PATHOGENS BEING TARGETED. THEIR EFFORTS ARE ORGANIZED INTO FIVE SYNERGISTIC PROJECTS SUPPORTED BY CUTTING-EDGE TECHNICAL EXPERTISE IN FIVE AC/DC SCIENTIFIC CORES, COVERING KEY AREAS OF PRECLINICAL DRUG DISCOVERY AND DEVELOPMENT. A NUMBER OF THE CORE LEADERS HAVE SIGNIFICANT EXPERIENCE IN THE DEVELOPMENT OF ANTIVIRALS IN THE PHARMA AND BIOTECHNOLOGY SECTORS. THE AC/DC WILL ACHIEVE ITS OVERARCHING GOAL IN TWO MAJOR OBJECTIVES. PILOT STUDIES IDENTIFIED TWO CHEMICALLY DISTINCT BROAD-SPECTRUM RIBONUCLEOSIDE ANALOGS AND TWO NON-NUCLEOSIDE VIRAL POLYMERASE INHIBITORS WITH CONFIRMED ORAL EFFICACY AGAINST ONE OR SEVERAL OF THE FIVE VIRAL FAMILIES TARGETED, INCLUDING A NOVEL CHEMOTYPE THAT IS ORALLY EFFICACIOUS AGAINST SARS-COV-2 IN RELEVANT ANIMAL MODELS. OBJECTIVE 1 WILL ADVANCE THIS SET OF FOUR NOVEL DAA LEADS THROUGH FINAL SYNTHETIC OPTIMIZATION AND DE-RISKING IN ANIMAL MODELS AND PRIMARY HUMAN ORGANOIDS AS IMMEDIATE DELIVERABLES TO MITIGATE THE URGENT THREAT TO PUBLIC HEALTH. SIMULTANEOUSLY, OBJECTIVE 2 WILL IDENTIFY ADDITIONAL VIABLE HIT CHEMOTYPES TO EXPAND THE AC/DC'S ANTIVIRAL PORTFOLIO BY LEVERAGING CENTER EXPERTISE IN REVERSE GENETICS OF ALL VIRAL TARGET FAMILIES, EXISTING GROUNDBREAKING REPORTER VIRUS TECHNOLOGIES, AND HIGH-THROUGHPUT SCREENING UNDER STANDARD AND HIGH BIOCONTAINMENT CONDITIONS. HITS WILL BE COUNTERSCREENED AGAINST ALL CENTER TARGET FAMILIES, MOLECULAR VIRAL TARGETS AND MECHANISM OF ACTION CHARACTERIZED, AND A POTENCY, PHARMACOKINETICS, AND PHARMACOPHORE-DRIVEN SYNTHETIC DEVELOPMENT PROGRAM LAUNCHED TO IDENTIFY OPTIMIZED LEADS. ALL DATA GENERATED BY THE PROJECTS AND CORES WILL BE EVALUATED CENTER-WIDE UTILIZING QUANTITATIVE PERFORMANCE MILESTONES OF A DEFINED AC/DC LEAD ADVANCEMENT CASCADE THAT GOVERNS THE PROGRESSION OF A CHEMOTYPE FROM HIT TO CLINICAL DEVELOPMENT CANDIDATE."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"EMORY UNIVERSITY","value":28013664,"savings":4141688,"link":null,"description":"This Infectious Diseases Clinical Research Consortium Leadership Group (IDCRCLG or LG) is a new, collaborative national partnership of leading infectious diseases, human immunology and clinical research experts from eight outstanding academic institutions providing experience, guidance, global connectivity and innovative approaches to address NIH/NIAID clinical research priorities. The emphasis (and strength) of the IDCRCLG is to facilitate, plan and help implement clinical research for respiratory and enteric infections, malaria/tropical diseases, and sexually transmitted infections (STIs), and to respond to emerging infectious diseases (EID). Priority research will include interventional trials and clinical research studies for vaccines, biologics, therapeutics, diagnostics and devices targeting these infectious diseases. The LG’s experts and their programs at the eight universities and beyond have a historic record of accomplishment in vaccine and therapeutic clinical research, and immunologic and pathogenesis studies for these NIAID-priority infectious diseases. The LG brings extensive expertise with the conduct of Phase I-IV clinical trials including first- in-human studies, cutting-edge human immunology, pharmacokinetics; engagement with diverse populations both nationally/internationally, sIRBs, innovative public-private partnerships, and Investigational New Drug applications (INDs). The group also has strong connectivity to and will leverage NIH/NIAID-supported networks; extensive experience in collaborating with industry partners and foundations, and leadership of complex administrative consortia. This cadre of diverse infectious diseases experts proposes to establish and operate with NIAID and the reconstituted Vaccine and Treatment Evaluation Units (VTEUs), an integrated, highly- functional, efficient IDCRC to develop innovative scientific and operational strategies in priorities such as vaccines and STI clinical research. The organizational structure supporting the science and operations of the IDCRCLG is composed of a Leadership Operations Center including Expert Working Groups, a Clinical Operations Unit, a Laboratory Operations Unit, and a Statistical and Data Science Unit. Key functions of the LG are to propose, review and prioritize innovative concepts; to enhance integration and efficiency in operations; to form collaborative teams; to ensure quality and timely protocol implementation; to disseminate the results; to promote integration of all populations in IDCRC research across the human lifespan; and to attract, engage and retain the next generation of scientists in infectious diseases clinical research. In addition, the LG’s experience with EID threats, links to global partners/sites, access to the highest-level clinical and laboratory containment facilities and to large populations will help the IDCRC to respond rapidly (surge capacity) during a public health emergency. The LG’s decades of experience with public health, regulatory agencies, product development pipelines further enhance this capacity. The IDCRCLG and the institutions they represent are committed through dedicated PI/leadership effort, space, infrastructure and direct funds to develop the IDCRC."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"EMORY UNIVERSITY","value":14870022,"savings":1038689,"link":null,"description":"Project Summary/Abstract The currently NIAID-funded Vaccine and Treatment Evaluation Unit (VTEU) based at Emory University is ideally positioned to implement the mission of the Infectious Diseases Clinical Research Consortium (IDCRC) . The Emory VTEU is supported by Emory's rich scientific milieu with numerous synergistic grants and various thematic research centers covering all IDCRC scientific priority areas. The Emory VTEU infrastructure relies on two clinical research sites with a total of 16,000 square feet of clinical, laboratory, and pharmacy space and 83 faculty members and staff. Over the past decade as a funded VTEU, we have conducted 51 VTEU protocols, served as lead on 25 trials, performed endpoint assays for 17 studies, and published 22 high impact papers. We have enrolled ~3,000 participants, 55% are female and 37% from diverse racial and ethnic backgrounds with a retention rate of ~93%. With its flexible infrastructure, the Emory VTEU demonstrated surge capacity to contribute to pandemic influenza, Zika, Ebola, and biodefense efforts by prioritizing resources in funds and staffing. The Emory VTEU will build on the current surge capacity by strengthening our partnership with the Georgia Clinical and Translational Science Alliance and collaborating with well-established Emory international partners on a protocol-specific basis. Additionally, to date, our VTEU has trained 28 fellows and junior faculty. We will build on our significant record of accomplishment and advance the IDCRC mission by implementing the following specific aims: 1. Engage a broad range of Emory scientists with expertise in established and newly emerging infectious diseases in the core science of the IDCRC including concept generation and protocol development. 2. Leverage our access to a unique and diverse population and state-of-the-art research infrastructure to implement all components of the IDCRC science, including study conduct, data quality control and assurance procedures, data management, and good clinical, laboratory, and pharmacy practices. 3. Optimize our operational flexibility to further enhance our ability to provide surge capacity to address emerging infectious diseases and pandemic response. 4. Expand our mentoring capacity and enhance career development opportunities for early stage investigators in the areas of vaccinology, infectious diseases diagnostics, therapeutics, and prevention."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"EMORY UNIVERSITY","value":12203207,"savings":795325,"link":null,"description":"Project Summary/Abstract The currently NIAID-funded Vaccine and Treatment Evaluation Unit (VTEU) based at Emory University is ideally positioned to implement the mission of the Infectious Diseases Clinical Research Consortium (IDCRC) . The Emory VTEU is supported by Emory's rich scientific milieu with numerous synergistic grants and various thematic research centers covering all IDCRC scientific priority areas. The Emory VTEU infrastructure relies on two clinical research sites with a total of 16,000 square feet of clinical, laboratory, and pharmacy space and 83 faculty members and staff. Over the past decade as a funded VTEU, we have conducted 51 VTEU protocols, served as lead on 25 trials, performed endpoint assays for 17 studies, and published 22 high impact papers. We have enrolled ~3,000 participants, 55% are female and 37% from diverse racial and ethnic backgrounds with a retention rate of ~93%. With its flexible infrastructure, the Emory VTEU demonstrated surge capacity to contribute to pandemic influenza, Zika, Ebola, and biodefense efforts by prioritizing resources in funds and staffing. The Emory VTEU will build on the current surge capacity by strengthening our partnership with the Georgia Clinical and Translational Science Alliance and collaborating with well-established Emory international partners on a protocol-specific basis. Additionally, to date, our VTEU has trained 28 fellows and junior faculty. We will build on our significant record of accomplishment and advance the IDCRC mission by implementing the following specific aims: 1. Engage a broad range of Emory scientists with expertise in established and newly emerging infectious diseases in the core science of the IDCRC including concept generation and protocol development. 2. Leverage our access to a unique and diverse population and state-of-the-art research infrastructure to implement all components of the IDCRC science, including study conduct, data quality control and assurance procedures, data management, and good clinical, laboratory, and pharmacy practices. 3. Optimize our operational flexibility to further enhance our ability to provide surge capacity to address emerging infectious diseases and pandemic response. 4. Expand our mentoring capacity and enhance career development opportunities for early stage investigators in the areas of vaccinology, infectious diseases diagnostics, therapeutics, and prevention."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"EMORY UNIVERSITY","value":26794157,"savings":661081,"link":null,"description":"The overarching objective of the Emory Autoimmunity Center of Excellence (ACE) U19 is to decipher the molecular programs responsible for the aberrant B cell responses underpinning autoimmune diseases. A central tenet of the Emory ACE is that unraveling the heterogeneity of human autoimmune diseases and translating that knowledge into mechanistically based treatments requires an integrated collaboration between physician-scientists, basic scientists, and expert clinicians with access to large populations of well-characterized autoimmune patients. Our fundamental goals are: (1) to understand B cell dysregulation in SLE using single cell interrogation of their molecular roadmaps, and (2) to assemble a scientific and technological platform that engages other ACE U19 and UM1 Centers through the Collaborative Project to perform similar studies in other immune cells and autoimmune disorders. These goals will be realized through a highly integrated collaboration between the three components of the Scientific Program supported by an Administrative Core. In the Principal Project, Dr. Sanz will ascertain the heterogeneity of effector B cells, their regulatory programs, and their differential utilization according to disease endotypes, and investigate the diversity and regulation of SLE memory cells. Specifically, his group will analyze germinal center dependent and independent memory and the role of antigenic persistence in the regulation of autoimmune and protective memory. In the Collaborative Project, Dr. Boss will investigate the epigenetic regulation of B cells and other immune cells in SLE and other human autoimmune diseases as part of the Collaborative Agenda that will be developed within the new ACE centers. Finally, in the Pilot Project, Dr. Scharer will pursue the functional characterization of SLE B cell differentiation using high-throughput loss-of-function and gain-of- function CRISPR screens. The Emory ACE also proposes to continue to manage the ACE Funds Management Core and to establish a centralized ACE Biorepository Core to coordinate the collection, storage, and management of samples from the Emory ACE and ACE Clinical Projects and their allocation for use in mechanistic studies. Collectively, the work proposed should contribute greatly to the charter mission and goals of the Autoimmunity Centers of Excellence Network."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"EMORY UNIVERSITY","value":1332148,"savings":179492,"link":null,"description":"PROJECT SUMMARY/ABSTRACT COVID-19 was first identified in December 2019 in Wuhan, Hubei province, China, resulting in the ongoing 2019- 2020 pandemic. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV- 2). Common symptoms of the disease include fever, dry cough, shortness of breath, diarrhea, and loss of smell. Complications may include pneumonia, viral sepsis, and acute respiratory distress syndrome. As of today, other than remdesivir, there is no approved small molecule drug for the treatment of COVID-19 and the discovery of an effective vaccine remains uncertain. Our long-term goal is to develop antiviral drugs for the treatment of COVID-19 and human coronavirus infections in general. Our central hypothesis is that inhibition of SARS-CoV- 2 polyprotein cleavage results in the prevention and early treatment of COVID-19 before it progresses to its more severe form. We will identify nanomolar inhibitors of the CoV 3C-like protease (3CLpro) suitable to be developed as antiviral agents for the treatment of COVID-19 and other coronavirus infections. The proposal targets the 3CLpro, a key enzyme for SARS-CoV-2 polyprotein cleavage and viral replication. Our overall premise is that small molecule inhibitors targeting this essential viral enzyme will inhibit replication, and therefore have the potential to be of both preventive and therapeutic value. Thus, our primary objective is to design and develop structure-based small-molecule inhibitors targeting coronavirus 3CLpro using our established and proven drug discovery expertise. Guided by strong preliminary data, the inhibition of polyprotein cleavage hypothesis will be tested by pursuing three specific aims: Aim 1) To inhibit SARS-CoV-2 polyprotein cleavage by developing covalent peptidic inhibitors of 3CLpro (nsp5).; Aim 2) To inhibit SARS-CoV-2 polyprotein cleavage by developing noncovalent nonpeptidic inhibitors of 3CLpro (nsp5).; and Aim 3) To determine the efficacy of covalent and noncovalent SARS-CoV-2 3CLpro inhibitors in a golden hamster model. Under the first aim, lead compound 3150 and its analogs will be tested in viral and enzyme assays for inhibitory activity of SARS-CoV-2 3CLpro. An aqueous soluble form of 3150 will be evaluated in the animal model. Structure-based drug design approaches will be employed to optimize 3150 for binding to the crystal structure of SARS-CoV-2 3CLpro. Under aim 2, Structure-based virtual screening and hybrid ligand screening approaches along with medicinal chemistry will be used to prepare and evaluate noncovalent nonpeptidic inhibitors of 3CLpro. Under the third aim, top-ranked SARS-CoV-2 3CLpro covalent and noncovalent inhibitors will be tested for pharmacokinetics and efficacy in a golden hamster COVID-19 model. The ultimate goal of the proposed studies is to advance an anti-COVID-19 drug candidate to the stage of filing an investigational new drug (IND) application. Overall, the results of this project will have a significant positive impact because they lay the groundwork for the clinical development of COVID-19 antiviral therapy and the potential to combine a potent and selective protease inhibitor with a nucleoside analog (e.g., remdesivir) and if needed anti-inflammatory drugs (e.g., dexamethasone or baricitinib)."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"EMORY UNIVERSITY","value":6662234,"savings":127333,"link":null,"description":"POPULATION-BASED SURVEY OF SARS-COV-2 INFECTION AND IMMUNE RESPONSE"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"FRED HUTCHINSON CANCER CENTER","value":31842477,"savings":8037749,"link":null,"description":"Project Abstract Efforts to control the pandemic have resulted in widespread shelter-in-place orders. Transmission of SARS- CoV-2 occurs primarily through person-to-person contact and respiratory droplet transmission (Lai,2020). Household contacts of a person infected with SARS-CoV-2 are at a high risk for acquiring infection, with transmission rates ranging from approximately 10% to 15%. The majority of individuals who acquire infection from household contacts develop symptoms of COVID-19(Burke,2020) (Jing, 2020), (Bi,2020) (Li,2020b). Prophylaxis is urgently needed to reduce transmission rates and/or reduce the occurrence of symptomatic disease. Ideally, prophylaxis would need to be given as soon as possible after a known exposure, as the duration of time between symptomatic infection in the source individual and the development of symptoms in newly infected individual is thought to be approximately 5 days, with a possible range of 2 to14 days(Lauer,2020) (Li,2020a). Animal models suggest that SARS-CoV-2 RT-PCR in nasopharyngeal (NP) samples become positive within a few days after infection (Rockx,2020). An ideal agent for prophylaxis should be fast acting and highly effective and should protect against multiple viral variants. A monoclonal antibody (mAb) combination therapy, with two different monoclonal antibodies that bind distinct regions of the portion of the SARS-CoV-2 spike(S) protein that bind to and facilitate entry into host cells, has been developed in order to achieve these goals. A mAb combination against SARS-CoV-2 for post-exposure prophylaxis that can either prevent the development of disease or reduce viral acquisition or shedding could be key to reducing transmission of the virus and limiting symptoms and adverse outcomes following infection. Currently, however, there is no approved prophylaxis for COVID-19 nor for patients that are infected with SARS-CoV-2 but are asymptomatic. Given the speed at which this outbreak has spread and how it has impacted almost every community globally, there is an urgent need to develop safe and efficacious interventions to slow the spread of the SARS-CoV-2 virus and decrease adverse outcomes associated with symptomatic disease. This is a pivotal phase 3 randomized, double-blind, placebo-controlled study in adults with household contact exposure to individuals with SARS-CoV-2 infection in geographic areas with an active COVID-19 outbreak. This study is designed to assess the efficacy and safety of co-administered REGN10933+REGN10987 combination therapy (“REGN10933+REGN10987”) to reduce the proportion of SARS-CoV-2 infections and prevent the development of COVID-19 disease (symptomatic SARS-CoV2 infection), after household exposure to individuals with SARS-CoV-2 infection. Safety, tolerability, pharmacokinetics (PK), and immunogenicity of REGN10933+REGN10987 will also be evaluated."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"FRED HUTCHINSON CANCER CENTER","value":21274991,"savings":7503715,"link":null,"description":"FOA: PA-20-272: Administrative Supplements to Existing NIH Grants and Cooperative Agreements Activity Code/Award: UM1/A1068614-15 (parent award) ------------------------------------------------------------------------------------ Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial entitled “A parallel-group, Phase III, multi-stage, modified double-blind, multi-armed study to assess the efficacy, safety, and immunogenicity of two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (monovalent and bivalent) for prevention against COVID-19 in adults 18 years of age and older.” With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 in SARS-CoV-2 infected individuals. Addressing this gap, the National Institutes of Health (NIH) led rapid constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of physician-scientists at 145 United States (US) and 71 international clinical trial sites in 17 countries dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the LOC for CoVPN vaccine trials. This Phase 3, multi-stage, modified double-blind, placebo-controlled, multi-armed study will test the efficacy, safety and immunogenicity of Sanofi-Pasteur SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, monovalent D614 (monovalent vaccine) & SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, bivalent D614/B.1.351 (bivalent vaccine), to modify COVID-19 disease in adults 18 years of age and older. Participants will be recruited from clinical trial sites across the US and globally using data analytics to target high risk individuals with a diverse racial and ethnic profile. Participants will receive symptomatic screening for SARS-CoV-2 infection, and if they become infected will be monitored with frequent clinical check-ins and remote monitoring of vital signs. Infected individuals who progress to moderate-severe COVID-19 will be referred for hospitalization. All trial endpoint assays will be done using qualified and validated assays for diagnosis and immune monitoring. Specific aims of this study are to assess the clinical efficacy of the investigational CoV2 preS dTM recombinant protein adjuvanted with AS03 – both monovalent and bivalent (“study vaccines”) in naïve adults for the prevention of symptomatic COVID-19 occurring > 14 days after the second injection; to assess the safety of the study vaccines compared to placebo throughout the study; to assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for prevention of the following occurring > 14 days after the second injection: prevention of SARS-CoV-2 infection, prevention of severe COVID-19; to describe the frequency & spectrum of disease in episodes of symptomatic COVID-19 in SARS-CoV-2 non-naïve adults in each study group. This efficacy trial will tell us much about the ability of two recombinant vaccines, targeting two of the most common SARS-CoV-2 variants, to induce strong adaptive protective responses. After the Novavax vaccine, this is the second large scale recombinant protein vaccine to be tested for efficacy and it is the first trial to use a bivalent vaccine including the B.1.351 variant of concern. If successful, this will be an important vaccine that can be scaled up rapidly and deployed throughout the world. The results of this trial will be used to assess registration of this vaccine product and will also provide crucial information to inform future generations of COVID-19 vaccines."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"FRED HUTCHINSON CANCER CENTER","value":83440030,"savings":7393274,"link":null,"description":"Project Abstract Efforts to control the pandemic have resulted in widespread shelter-in-place orders. Transmission of SARS- CoV-2 occurs primarily through person-to-person contact and respiratory droplet transmission (Lai,2020). Household contacts of a person infected with SARS-CoV-2 are at a high risk for acquiring infection, with transmission rates ranging from approximately 10% to 15%. The majority of individuals who acquire infection from household contacts develop symptoms of COVID-19(Burke,2020) (Jing, 2020), (Bi,2020) (Li,2020b). Prophylaxis is urgently needed to reduce transmission rates and/or reduce the occurrence of symptomatic disease. Ideally, prophylaxis would need to be given as soon as possible after a known exposure, as the duration of time between symptomatic infection in the source individual and the development of symptoms in newly infected individual is thought to be approximately 5 days, with a possible range of 2 to14 days(Lauer,2020) (Li,2020a). Animal models suggest that SARS-CoV-2 RT-PCR in nasopharyngeal (NP) samples become positive within a few days after infection (Rockx,2020). An ideal agent for prophylaxis should be fast acting and highly effective and should protect against multiple viral variants. A monoclonal antibody (mAb) combination therapy, with two different monoclonal antibodies that bind distinct regions of the portion of the SARS-CoV-2 spike(S) protein that bind to and facilitate entry into host cells, has been developed in order to achieve these goals. A mAb combination against SARS-CoV-2 for post-exposure prophylaxis that can either prevent the development of disease or reduce viral acquisition or shedding could be key to reducing transmission of the virus and limiting symptoms and adverse outcomes following infection. Currently, however, there is no approved prophylaxis for COVID-19 nor for patients that are infected with SARS-CoV-2 but are asymptomatic. Given the speed at which this outbreak has spread and how it has impacted almost every community globally, there is an urgent need to develop safe and efficacious interventions to slow the spread of the SARS-CoV-2 virus and decrease adverse outcomes associated with symptomatic disease. This is a pivotal phase 3 randomized, double-blind, placebo-controlled study in adults with household contact exposure to individuals with SARS-CoV-2 infection in geographic areas with an active COVID-19 outbreak. This study is designed to assess the efficacy and safety of co-administered REGN10933+REGN10987 combination therapy (“REGN10933+REGN10987”) to reduce the proportion of SARS-CoV-2 infections and prevent the development of COVID-19 disease (symptomatic SARS-CoV2 infection), after household exposure to individuals with SARS-CoV-2 infection. Safety, tolerability, pharmacokinetics (PK), and immunogenicity of REGN10933+REGN10987 will also be evaluated."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"FRED HUTCHINSON CANCER CENTER","value":9626428,"savings":5000422,"link":null,"description":"FOA: PA-20-272: Administrative Supplements to Existing NIH Grants and Cooperative Agreements Activity Code/Award: UM1/A1068614-15 (parent award) ------------------------------------------------------------------------------------ Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial entitled “A parallel-group, Phase III, multi-stage, modified double-blind, multi-armed study to assess the efficacy, safety, and immunogenicity of two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (monovalent and bivalent) for prevention against COVID-19 in adults 18 years of age and older.” With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 in SARS-CoV-2 infected individuals. Addressing this gap, the National Institutes of Health (NIH) led rapid constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of physician-scientists at 145 United States (US) and 71 international clinical trial sites in 17 countries dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the LOC for CoVPN vaccine trials. This Phase 3, multi-stage, modified double-blind, placebo-controlled, multi-armed study will test the efficacy, safety and immunogenicity of Sanofi-Pasteur SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, monovalent D614 (monovalent vaccine) & SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, bivalent D614/B.1.351 (bivalent vaccine), to modify COVID-19 disease in adults 18 years of age and older. Participants will be recruited from clinical trial sites across the US and globally using data analytics to target high risk individuals with a diverse racial and ethnic profile. Participants will receive symptomatic screening for SARS-CoV-2 infection, and if they become infected will be monitored with frequent clinical check-ins and remote monitoring of vital signs. Infected individuals who progress to moderate-severe COVID-19 will be referred for hospitalization. All trial endpoint assays will be done using qualified and validated assays for diagnosis and immune monitoring. Specific aims of this study are to assess the clinical efficacy of the investigational CoV2 preS dTM recombinant protein adjuvanted with AS03 – both monovalent and bivalent (“study vaccines”) in naïve adults for the prevention of symptomatic COVID-19 occurring > 14 days after the second injection; to assess the safety of the study vaccines compared to placebo throughout the study; to assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for prevention of the following occurring > 14 days after the second injection: prevention of SARS-CoV-2 infection, prevention of severe COVID-19; to describe the frequency & spectrum of disease in episodes of symptomatic COVID-19 in SARS-CoV-2 non-naïve adults in each study group. This efficacy trial will tell us much about the ability of two recombinant vaccines, targeting two of the most common SARS-CoV-2 variants, to induce strong adaptive protective responses. After the Novavax vaccine, this is the second large scale recombinant protein vaccine to be tested for efficacy and it is the first trial to use a bivalent vaccine including the B.1.351 variant of concern. If successful, this will be an important vaccine that can be scaled up rapidly and deployed throughout the world. The results of this trial will be used to assess registration of this vaccine product and will also provide crucial information to inform future generations of COVID-19 vaccines."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"FRED HUTCHINSON CANCER CENTER","value":4948110,"savings":3435996,"link":null,"description":"FOA: PA-20-272: Administrative Supplements to Existing NIH Grants and Cooperative Agreements Activity Code/Award: UM1/A1068614-15 (parent award) ------------------------------------------------------------------------------------ Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial entitled “A parallel-group, Phase III, multi-stage, modified double-blind, multi-armed study to assess the efficacy, safety, and immunogenicity of two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (monovalent and bivalent) for prevention against COVID-19 in adults 18 years of age and older.” With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 in SARS-CoV-2 infected individuals. Addressing this gap, the National Institutes of Health (NIH) led rapid constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of physician-scientists at 145 United States (US) and 71 international clinical trial sites in 17 countries dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the LOC for CoVPN vaccine trials. This Phase 3, multi-stage, modified double-blind, placebo-controlled, multi-armed study will test the efficacy, safety and immunogenicity of Sanofi-Pasteur SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, monovalent D614 (monovalent vaccine) & SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, bivalent D614/B.1.351 (bivalent vaccine), to modify COVID-19 disease in adults 18 years of age and older. Participants will be recruited from clinical trial sites across the US and globally using data analytics to target high risk individuals with a diverse racial and ethnic profile. Participants will receive symptomatic screening for SARS-CoV-2 infection, and if they become infected will be monitored with frequent clinical check-ins and remote monitoring of vital signs. Infected individuals who progress to moderate-severe COVID-19 will be referred for hospitalization. All trial endpoint assays will be done using qualified and validated assays for diagnosis and immune monitoring. Specific aims of this study are to assess the clinical efficacy of the investigational CoV2 preS dTM recombinant protein adjuvanted with AS03 – both monovalent and bivalent (“study vaccines”) in naïve adults for the prevention of symptomatic COVID-19 occurring > 14 days after the second injection; to assess the safety of the study vaccines compared to placebo throughout the study; to assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for prevention of the following occurring > 14 days after the second injection: prevention of SARS-CoV-2 infection, prevention of severe COVID-19; to describe the frequency & spectrum of disease in episodes of symptomatic COVID-19 in SARS-CoV-2 non-naïve adults in each study group. This efficacy trial will tell us much about the ability of two recombinant vaccines, targeting two of the most common SARS-CoV-2 variants, to induce strong adaptive protective responses. After the Novavax vaccine, this is the second large scale recombinant protein vaccine to be tested for efficacy and it is the first trial to use a bivalent vaccine including the B.1.351 variant of concern. If successful, this will be an important vaccine that can be scaled up rapidly and deployed throughout the world. The results of this trial will be used to assess registration of this vaccine product and will also provide crucial information to inform future generations of COVID-19 vaccines."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"FRED HUTCHINSON CANCER CENTER","value":18398956,"savings":414175,"link":null,"description":"Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial entitled “Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS-CoV-2 Variants of Concern.” With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 in SARS-CoV-2 infected individuals. Addressing this gap, the National Institutes of Health (NIH) led rapid constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of physician-scientists at 145 United States (US) and 71 international clinical trial sites in 17 countries dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the LOC for CoVPN vaccine trials. This Phase 3, observer-blinded, placebo-controlled, crossover-vaccination study will test the efficacy of the COVID-19 ancestral strain mRNA vaccine in preventing COVID-19 disease regardless of severity, and preventing COVID-19 severe disease in people who are at risk for severe COVID-19 in areas of the world where the prevalence of the SARS-CoV-2 1.351 strain is substantial. The trial has been designed to provide as rapid assessment of efficacy as possible in regions of the world where local access to effective vaccines are limited. Subjects will be randomized in a 1:1 ratio to receive immediate or deferred vaccine. The blinded cross-over is expected to take place when vaccine benefit is declared based on at least 50 primary COVID-19 endpoints, anticipated to be accrued approximately 3 months post-trial start. All trial endpoint assays will be done using qualified and validated assays for diagnosis and immune monitoring. Specific aims of this study are to demonstrate efficacy of COVID-19 mRNA (Moderna mRNA-1273) vaccine to prevent virologically-confirmed symptomatic COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19; to assess vaccine efficacy of COVID-19 mRNA vaccine to prevent severe COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19; and to assess safety and tolerability of COVID-19 mRNA vaccine in adults who are at risk of severe COVID-19. This efficacy trial will tell us much about ability of an mRNA vaccine against the ancestral Wuhan strain of SARS-CoV-2 to protect individuals exposed to divergent strains, and in particular 1.351 first predominant in South Africa. In addition, it will improve our understanding of the dynamics and duration of these immune responses and will inform rational design and testing of preventive and therapeutic monoclonal antibody interventions in parts of the world where alternative strains continue to proliferate. Lastly, the results of this trial will be used to assess registration of this vaccine product as well as to modify future COVID-19 vaccine trials planned over the next 12 months."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"FRED HUTCHINSON CANCER CENTER","value":12647369,"savings":293722,"link":null,"description":"Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial entitled “Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS-CoV-2 Variants of Concern.” With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 in SARS-CoV-2 infected individuals. Addressing this gap, the National Institutes of Health (NIH) led rapid constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of physician-scientists at 145 United States (US) and 71 international clinical trial sites in 17 countries dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the LOC for CoVPN vaccine trials. This Phase 3, observer-blinded, placebo-controlled, crossover-vaccination study will test the efficacy of the COVID-19 ancestral strain mRNA vaccine in preventing COVID-19 disease regardless of severity, and preventing COVID-19 severe disease in people who are at risk for severe COVID-19 in areas of the world where the prevalence of the SARS-CoV-2 1.351 strain is substantial. The trial has been designed to provide as rapid assessment of efficacy as possible in regions of the world where local access to effective vaccines are limited. Subjects will be randomized in a 1:1 ratio to receive immediate or deferred vaccine. The blinded cross-over is expected to take place when vaccine benefit is declared based on at least 50 primary COVID-19 endpoints, anticipated to be accrued approximately 3 months post-trial start. All trial endpoint assays will be done using qualified and validated assays for diagnosis and immune monitoring. Specific aims of this study are to demonstrate efficacy of COVID-19 mRNA (Moderna mRNA-1273) vaccine to prevent virologically-confirmed symptomatic COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19; to assess vaccine efficacy of COVID-19 mRNA vaccine to prevent severe COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19; and to assess safety and tolerability of COVID-19 mRNA vaccine in adults who are at risk of severe COVID-19. This efficacy trial will tell us much about ability of an mRNA vaccine against the ancestral Wuhan strain of SARS-CoV-2 to protect individuals exposed to divergent strains, and in particular 1.351 first predominant in South Africa. In addition, it will improve our understanding of the dynamics and duration of these immune responses and will inform rational design and testing of preventive and therapeutic monoclonal antibody interventions in parts of the world where alternative strains continue to proliferate. Lastly, the results of this trial will be used to assess registration of this vaccine product as well as to modify future COVID-19 vaccine trials planned over the next 12 months."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"HACKENSACK MEDICAL CENTER","value":65141731,"savings":16434139,"link":null,"description":"METROPOLITAN ANTIVIRAL DRUG ACCELERATOR - ABSTRACT THE COVID-19 PANDEMIC CAUSED BY SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) HAS RESULTED IN MILLIONS OF DEATHS WORLDWIDE. NOVEL VACCINES AGAINST SARS-COV-2 HAVE ALTERED THE PANDEMIC’S TRAJECTORY. YET, LARGE POPULATIONS REMAIN AT RISK, AND IMMUNE ESCAPE VIRUS VARIANTS THREATEN TO THWART VACCINE ACTION OR CURRENT THERAPIES. NEW SMALL MOLECULE ANTIVIRAL DRUGS AVAILABLE AS ORAL TREATMENTS IN THE OUTPATIENT SETTING ARE NEEDED TO TREAT SARS-COV-2 INFECTIONS, OTHER CORONAVIRUSES, AND ADDITIONAL VIRUSES OF PANDEMIC CONCERN. COVID-19 HAS HELPED REJOIN LARGE PHARMA IN ANTI-INFECTIVE DRUG DEVELOPMENT BUT THERE REMAINS A GAP IN THE EARLY DRUG DISCOVERY PHASE, WHICH CAN BE MET BY ACADEMIC SCIENTISTS ENGAGED IN DRUG DISCOVERY THROUGH SUCCESSFUL PARTNERSHIP WITH INDUSTRY. ACADEMIC GROUPS HAVE GREAT BIOLOGICAL INSIGHTS AND PLATFORMS FOR NOVEL DISCOVERY RESULTING IN IDENTIFICATION OF NEW TARGETS, HITS, AND LEADS. YET, THEY RARELY HAVE THE WAYS OR MEANS TO OPTIMIZE COMPOUNDS AND ADVANCE THEM FOR CLINICAL DEVELOPMENT. WE HYPOTHESIZE THAT AN EFFECTIVE PUBLIC-PRIVATE PARTNERSHIP CAN BRIDGE THIS GAP AND HAVE CREATED THE METROPOLITAN ANTIVIRAL DRUG ACCELERATOR (MAVDA). IT IS AN UNPRECEDENTED COLLABORATIVE ENTERPRISE OF ACADEMIC AND PHARMA PARTNERS IN NEW YORK CITY AND NORTHERN NEW JERSEY BROUGHT TOGETHER IN A COMMON DISCOVERY ECOSYSTEM TO ADDRESS THE URGENT NEED FOR VALIDATED SMALL-MOLECULE ANTIVIRAL DRUGS. MAVDA COMBINES WORLD-CLASS VIROLOGISTS AND ACADEMIC DRUG DISCOVERY RESEARCHERS FROM ROCKEFELLER UNIVERSITY, COLUMBIA UNIVERSITY AND MEMORIAL SLOAN- KETTERING CANCER CENTER IN NEW YORK CITY AND THE CENTER FOR DISCOVERY AND INNOVATION AND RUTGERS UNIVERSITY IN NEW JERSEY WITH PROVEN ANTIVIRAL DRUG DEVELOPERS AT MERCK & CO., INC., THE TRI-INSTITUTIONAL THERAPEUTICS DISCOVERY INSTITUTE (TRI-I TDI)-TAKEDA PHARMACEUTICALS, AND ALIGOS THERAPEUTICS, AS A COHESIVE ENTERPRISE TO DELIVER NEW ANTIVIRAL DRUGS. A CRITICAL INNOVATION OF THE ACCELERATOR IS THE ESTABLISHMENT OF AN EXTENSIVE AND INTEGRATED NETWORK OF PHARMA-STYLE SCIENCE CORES WITH HIGHLY EXPERIENCED CORE DIRECTORS, WHICH ENSURES THAT COMPOUND IDENTIFICATION AND OPTIMIZATION PROCEEDS EFFICIENTLY. STANDARDIZED THRESHOLD “GATING” METRICS FOR COMPOUND PROGRESSION WITH CLEAR ‘GO/NO GO’ CRITERIA WILL BE ESTABLISHED TO SUPPORT DEVELOPMENT OF QUALIFIED DRUG CANDIDATES. MAVDA PROJECTS UNITE ACADEMIC AND INDUSTRY INVESTIGATORS WITH INNOVATIVE AND WELL-ESTABLISHED DRUG DISCOVERY PLATFORMS WITH A STRONG EMPHASIS ON VALIDATED TARGETS LIKE 3CLPRO, BUT ALSO EXPLOIT OTHER IMPORTANT TARGETS LIKE NSP14 AND NSP16 MTASE, EXON, PLPRO, NSP13 HELICASE, RDRP, AS WELL AS NOVEL TARGETS. PROMISING HITS, EARLY LEADS, AND OPTIMIZED LEADS AT OR NEAR THE IND ENABLING/DE-RISKING STAGE ARE REPRESENTED, ALONG WITH INNOVATIVE APPROACHES FOR NEW NATURAL PRODUCT DISCOVERY. ALL PROGRAMS TARGET SARS-COV-2 BUT ALSO ADDRESS OTHER CORONAVIRUSES, FLAVIVIRUSES AND/OR ALPHAVIRUSES. MAVDA IS ROBUST, EASILY ACCOMMODATES DEVELOPMENTAL PROJECTS AND NEW VIRUS CHALLENGES, AND IT IS AN IDEAL ENVIRONMENT FOR TRAINING THE NEXT GENERATION OF SCIENTISTS FOR DRUG DISCOVERY AND PANDEMIC PREPAREDNESS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI","value":2314456,"savings":2002048,"link":null,"description":"STRENGTHENING THE ISMMS RESEARCH AND RESPONSE CAPABILITIES FOR PATHOGENS OF PANDEMIC POTENTIAL - THE ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI (ISMMS) IS AN INTERNATIONAL LEADER IN MEDICAL AND SCIENTIFIC TRAINING, BIOMEDICAL RESEARCH, AND PATIENT CARE. THE ISMMS IS THE MEDICAL SCHOOL FOR THE MOUNT SINAI HEALTH SYSTEM (MSHS), WHICH INCLUDES EIGHT HOSPITAL CAMPUSES WITHIN THE NEW YORK CITY METROPOLITAN AREA THAT IS A MAJOR FOCAL POINT OF INTERNATIONAL TRAVEL. THE MSHS LEVERAGED ITS LARGE METROPOLITAN FOOTPRINT BY ESTABLISHING PATHOGEN DISCOVERY AND PANDEMIC SURVEILLANCE ACTIVITIES. THE DEPARTMENT OF MICROBIOLOGY MAINTAINS ROBUST RESEARCH PROGRAMS THAT ARE FOCUSED ON INVESTIGATING THE BIOLOGY OF NEW AND EMERGING RNA VIRUSES WITH PANDEMIC POTENTIAL AND DEVELOPING NOVEL MEDICAL COUNTERMEASURES AGAINST THESE RNA THAT ARE FOCUS OF THE NIH ANTIVIRAL PROGRAM FOR PANDEMICS (APP). THESE RESEARCH PROGRAMS INCLUDE PANDEMIC PREPAREDNESS EFFORTS FOCUSED SEVEN RNA VIRUS FAMILIES OR ORDERS OF GREATEST PANDEMIC CONCERN, I.E., BUNYAVIRALES, CORONAVIRIDAE, FILOVIRIDAE, FLAVIVIRIDAE, PARAMYXOVIRIDAE, PICORNAVIRIDAE, AND TOGAVIRIDAE. SINCE 2017, FACULTY MEMBERS OF THE DEPARTMENT OF MICROBIOLOGY HAVE CO-AUTHORED OVER 250 PEER-REVIEWED PUBLICATIONS ON THESE VIRAL PATHOGENS OF PUBLIC HEALTH CONCERN. THE DEPARTMENT OF MICROBIOLOGY IS INTERNATIONALLY RECOGNIZED FOR ITS INFLUENZA RESEARCH PROGRAMS, INCLUDING INVESTIGATION OF HIGHLY PATHOGENIC INFLUENZA VIRUSES THAT REQUIRE ENHANCED BIOCONTAINMENT FACILITIES AND SAFETY PROTOCOLS. THE BSL-3/ABSL-3 BIOCONTAINMENT FACILITIES ARE ESSENTIAL SHARED RESOURCES THAT ENSURE BIOSAFETY AND BIOSECURITY OF RNA VIRUSES OF SIGNIFICANT PUBLIC HEALTH CONCERN AND TO SAFELY CONDUCT RESEARCH INVESTIGATING THE BIOLOGY OF VIRAL PATHOGENS WITH PANDEMIC POTENTIAL. OUR APPLICATION IS FOCUSED ON INFRASTRUCTURE IMPROVEMENTS TO MODERNIZE THREE BIOCONTAINMENT FACILITIES TO IMPROVE BIOSAFETY, IMPROVE EFFICIENCY OF OPERATIONS, AND EXPAND RESEARCH CAPABILITIES. THE FIRST AIM OF THE INFRASTRUCTURE IMPROVEMENTS FOCUS ON UPGRADES OF THE HVAC, AUTOCLAVES, BIOLOGICAL SAFETY CABINETS, AND VENTILATED ANIMAL CAGING SYSTEMS TO MODERNIZE AND IMPROVE THE EFFICIENCY OF OPERATIONS OF THE BIOCONTAINMENT FACILITIES. THE SECOND AIM OF THE INFRASTRUCTURE IMPROVEMENTS TO IMPROVE BIOCONTAINMENT RESEARCH WORKFLOW ON PATHOGENS WITH PANDEMIC POTENTIAL FOCUS, INCLUDING BIOTEK MULTIMODE MICROPLATE READERS, IMAGING STATIONS, AND A LUMINEX PLATFORM FOR MULTIPLEX IMMUNOASSAYS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"INTERNATIONAL FERTILITY RESEARCH PROGRAM","value":108743247,"savings":44188335,"link":null,"description":"Abstract: The novel virus, SARS-CoV-2, which causes Coronavirus Disease – 2019 (COVID-19) is a significant threat to public health. SARS-CoV-2 is both highly transmissible, as is evidenced by the current pandemic, and can lead to clinically significant COVID-19 disease. In severe and critical cases SARS-CoV-2 infection causes progressive pulmonary infection, complicated by respiratory failure, with a high prevalence of acute respiratory distress syndrome. Out of all age groups, older adults have the greatest risk of experiencing severe COVID-19 disease and its associated complications (CDC 2020; Grabowski and Mor 2020). Globally, there are a number of reports of COVID-19 rapidly spreading among the residents of skilled nursing facilities. Sadly, these nursing home residents also have high associated rates of both morbidity and mortality (Arons et al. 2020; Grabowski and Mor 2020; Graham et al. 2020). In the United States (US), at least 153,000 nursing home residents and employees have contracted COVID-19 disease and account for 35% of the country’s deaths (Werner et al. 2020). With more than 1.3 million Americans living in nursing homes (CDC 2016), there is an urgent need for effective, preventative strategies. CoVPN 3501 is a randomized, double-blind, placebo-controlled, prophylaxis study to evaluate the efficacy and safety of the intravenous mAb, LY3819253, in preventing SARS-CoV-2 infection and COVID-19, compared to placebo. It is expected that 1700-2400 participants (intent-to-treat [ITT] population) will be randomly assigned to study intervention such that approximately 1300 SARS-CoV-2 negative participants are randomized in the study with the goal of achieving approximately 33 events (in each of the primary and key secondary endpoints). This study will evaluate the effectiveness and safety of a monoclonal antibody (mAb), LY3819253, in preventing SARS-CoV-2 infection and COVID-19 disease in nursing home facility staff and residents."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"INTERNATIONAL FERTILITY RESEARCH PROGRAM","value":22082664,"savings":8787242,"link":null,"description":"Abstract: The novel virus, SARS-CoV-2, which causes Coronavirus Disease – 2019 (COVID-19) is a significant threat to public health. SARS-CoV-2 is both highly transmissible, as is evidenced by the current pandemic, and can lead to clinically significant COVID-19 disease. In severe and critical cases SARS-CoV-2 infection causes progressive pulmonary infection, complicated by respiratory failure, with a high prevalence of acute respiratory distress syndrome. Out of all age groups, older adults have the greatest risk of experiencing severe COVID-19 disease and its associated complications (CDC 2020; Grabowski and Mor 2020). Globally, there are a number of reports of COVID-19 rapidly spreading among the residents of skilled nursing facilities. Sadly, these nursing home residents also have high associated rates of both morbidity and mortality (Arons et al. 2020; Grabowski and Mor 2020; Graham et al. 2020). In the United States (US), at least 153,000 nursing home residents and employees have contracted COVID-19 disease and account for 35% of the country’s deaths (Werner et al. 2020). With more than 1.3 million Americans living in nursing homes (CDC 2016), there is an urgent need for effective, preventative strategies. CoVPN 3501 is a randomized, double-blind, placebo-controlled, prophylaxis study to evaluate the efficacy and safety of the intravenous mAb, LY3819253, in preventing SARS-CoV-2 infection and COVID-19, compared to placebo. It is expected that 1700-2400 participants (intent-to-treat [ITT] population) will be randomly assigned to study intervention such that approximately 1300 SARS-CoV-2 negative participants are randomized in the study with the goal of achieving approximately 33 events (in each of the primary and key secondary endpoints). This study will evaluate the effectiveness and safety of a monoclonal antibody (mAb), LY3819253, in preventing SARS-CoV-2 infection and COVID-19 disease in nursing home facility staff and residents."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"JOHNS HOPKINS UNIVERSITY","value":13641821,"savings":868175,"link":null,"description":"HOPE IN ACTION: A CLINICAL TRIAL OF HIV-TO-HIV LIVER TRANSPLANTATION"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"KAISER FOUNDATION RESEARCH INSTITUTE","value":9606309,"savings":3837357,"link":null,"description":"Abstract Infectious diseases continue to pose a significant threat to human health, with many types of infections having far-reaching, global consequences. The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat, and identify infectious diseases is a critical public health need. Clinical trials are an integral component of these development efforts. Since the 1960s the Vaccine and Treatment Evaluation Units (VTEUs) have conducted trials that have evaluated promising vaccine and therapeutic candidates for infectious diseases such as influenza (including pandemic and avian influenza), malaria, tuberculosis, pneumococcal infection, in children and adults. In addition, the VTEUs have quickly launched trials in response to newly emerging and reemerging infectious diseases, such as the 2009 influenza H1N1 pandemic, and Waves 1 and 5 of the H7N9 avian influenza outbreaks in China. These efforts have provided data that informed public health policy. This proposal is in response to a new VTEU structure which will involve greater collaboration between the VTEUs, NIAID, and the newly formed Leadership Group structure that are all part of the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC will enhance integration and efficiency of operations and, importantly, will foster the collaborative team science approaches now recognized as optimal to address important and complicated public health research priorities. Under the new cooperative agreement, the Kaiser Washington VTEU will continue to conduct clinical research and trials, including trials conducted under an IND or IDE, within the Kaiser Washington integrated care system to contribute to the priority research foci of NIAID. These priority areas include malaria, influenza and other respiratory infections, acute respiratory infections and include clinical trials, including human challenge models, and pharmacokinetic studies. The research will be conducted in collaboration with Seattle area infectious disease research partners who will provide scientific expertise, specialized facilities, and advanced immunologic laboratory capabilities. The Kaiser Washington VTEU will also develop and maintain surge capacity for clinical site, pharmacy and laboratory operations to enable the rapid initiation of clinical trials and other studies in response to emerging and reemerging infectious disease threats of public health importance."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"KAISER FOUNDATION RESEARCH INSTITUTE","value":7351141,"savings":1748994,"link":null,"description":"Abstract Infectious diseases continue to pose a significant threat to human health, with many types of infections having far-reaching, global consequences. The ability to develop vaccines, therapeutics, devices and diagnostics to prevent, treat, and identify infectious diseases is a critical public health need. Clinical trials are an integral component of these development efforts. Since the 1960s the Vaccine and Treatment Evaluation Units (VTEUs) have conducted trials that have evaluated promising vaccine and therapeutic candidates for infectious diseases such as influenza (including pandemic and avian influenza), malaria, tuberculosis, pneumococcal infection, in children and adults. In addition, the VTEUs have quickly launched trials in response to newly emerging and reemerging infectious diseases, such as the 2009 influenza H1N1 pandemic, and Waves 1 and 5 of the H7N9 avian influenza outbreaks in China. These efforts have provided data that informed public health policy. This proposal is in response to a new VTEU structure which will involve greater collaboration between the VTEUs, NIAID, and the newly formed Leadership Group structure that are all part of the NIAID Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC will enhance integration and efficiency of operations and, importantly, will foster the collaborative team science approaches now recognized as optimal to address important and complicated public health research priorities. Under the new cooperative agreement, the Kaiser Washington VTEU will continue to conduct clinical research and trials, including trials conducted under an IND or IDE, within the Kaiser Washington integrated care system to contribute to the priority research foci of NIAID. These priority areas include malaria, influenza and other respiratory infections, acute respiratory infections and include clinical trials, including human challenge models, and pharmacokinetic studies. The research will be conducted in collaboration with Seattle area infectious disease research partners who will provide scientific expertise, specialized facilities, and advanced immunologic laboratory capabilities. The Kaiser Washington VTEU will also develop and maintain surge capacity for clinical site, pharmacy and laboratory operations to enable the rapid initiation of clinical trials and other studies in response to emerging and reemerging infectious disease threats of public health importance."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"La Jolla Institute For Immunology","value":469233,"savings":340555,"link":null,"description":"HIPC DATA COORDINATING CENTER - PROJECT SUMMARY/ABSTRACT THE HUMAN IMMUNOLOGY PROJECT CONSORTIUM (HIPC) WAS FOUNDED IN 2010 TO CREATE A NETWORK OF INDEPENDENT CENTERS FOCUSED ON MEASURING HUMAN IMMUNE RESPONSES WITH HIGH-THROUGHPUT SYSTEMS IMMUNOLOGY APPROACHES COUPLED WITH DETAILED CLINICAL PHENOTYPING. WE PROPOSE TO DEVELOP A HIPC COORDINATING CENTER (HCC) THAT WILL PROVIDE DATA MORE RAPIDLY AND EFFECTIVELY TO THE BROADER SCIENTIFIC COMMUNITY, AND ALSO SERVE THE ENTIRE HIPC BY INCREASING THE VALUE OF THE RESEARCH PERFORMED AT HIPC CENTERS. IN PARALLEL, THE HCC WILL SERVE AS A PROMOTER OF CROSS-HIPC COLLABORATIONS THROUGH THE ORGANIZATION OF MULTI-CENTER ANALYSIS PROJECTS AND A CENTRALIZED PORTAL TO PROVIDE A SPACE FOR THE EXCHANGE OF IDEAS. SPECIFICALLY, THE HCC WILL CONTINUE THE DEVELOPMENT OF SHARED DATA STANDARDS, PROVIDE A CENTRAL KNOWLEDGEBASE OF STUDY RESULTS, ESTABLISH TOOLS TO VISUALIZE AND ANALYZE DATA, LEAD SYNERGISTIC CROSS-CENTER ANALYSIS EFFORTS, PROVIDE A PORTAL TO MAKE THE TOOLS AND DATA BROADLY ACCESSIBLE, AND PROVIDE ADMINISTRATIVE SUPPORT FOR THE ACTIVITIES OF HIPC SUBCOMMITTEES AND MANAGEMENT OF THE INFRASTRUCTURE AND OPPORTUNITY FUND (IOF) PROGRAM. OUR TEAM HAS PROVEN EXPERIENCE IN RUNNING PROGRAMS OF SIMILAR SCALE AND COMPLEXITY. WE ALSO HAVE THE NECESSARY FAMILIARITY WITH THE HIPC NETWORK, WITH OUR TEAM INCLUDING CURRENT PIS OF THE DATA STANDARDS IOF PROJECT, THE SIGNATURES IOF PROJECT, CLINICAL INFORMATION CAPTURE, AND THE EXISTING IMMUNESPACE DATA PORTAL. THIS PROPOSAL LEVERAGES THIS COMBINED EXPERIENCE AND INFRASTRUCTURE WHILE, IN PARALLEL, IMPLEMENTING VARIOUS SIGNIFICANT AND NECESSARY IMPROVEMENTS FACILITATED BY THE TIGHTER INTEGRATION AND THE 5-YEAR TIME HORIZON OF THIS DEDICATED HCC GRANT."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"NATIONAL JEWISH HEALTH","value":5963410,"savings":184249,"link":null,"description":"PROJECT SUMMARY/ABSTRACT Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the general population. AD is associated with defective skin barrier function, microbial dysbiosis, as well as various cutaneous immune abnormalities including type 2 inflammation and decreased cutaneous host defense. These abnormalities translate into multiple phenotypes and endotypes that are not fully defined and therefore, effective targeted therapies, beyond type 2 immune blockade, to reverse these various subsets of AD are lacking. Beyond its effects on cutaneous defense, AD is associated with systemic inflammation and appears to be the first step in the development of other atopic conditions including food allergy and asthma. This grant application is being submitted in response to RFA-AI-19-014, Atopic Dermatitis Research Network-Leadership Center (ADRN-LC). The goal of this proposal is to create an ADRN-LC which will provide the overall scientific strategy and organizational structure to the ADRN and will interact closely with the ADRN Clinical Research Centers (ADRN-CRCs), to support the conduct of multi-site clinical studies and trials that will elucidate mechanisms of skin barrier dysfunction and cutaneous immune responses in atopic dermatitis (AD). The central hypothesis in this application is that different phenotypes and endotypes of AD are associated with distinct defects in their skin barrier, microbiome, and skin immune responses which can be characterized by novel approaches to skin sampling and open up avenues for paradigm shifting therapeutic interventions to benefit patients with severe persistent AD. We will achieve our objectives with the following Aims: · Specific Aim 1: To establish an Administrative and Clinical Research Operations Leadership Center that will be responsible for implementation, coordination, and funding of clinical trials and studies for the ADRN-LC in research areas evaluating mechanism and treatment of AD. · Specific Aim 2: To develop a Network-wide multi-center ADRN clinical trial to evaluate the long- term effects of targeted microbiome transplantation on clinical outcomes in AD as well as epithelial barrier function, microbial dysbiosis, and cutaneous immunity. · Specific Aim 3: To design a Network-wide ADRN one-year observational study to assess the stability of AD phenotypes/endotypes using a Network correlation analysis of transcriptomics (conventional and single cell RNA sequencing), skin tape proteomics, lipidomics, and microbiome over time in subjects with persistent mild vs. persistent severe AD and assessment of therapeutic responses to topical corticosteroids and Dupilumab. · Specific Aim 4: To carry out a Network-wide multi-center ADRN clinical trial to examine the effects of targeted IL-1 blockade on the clinical outcome, skin microbiome, epithelial skin barrier, and cutaneous immune response in AD patients who have an inadequate response to IL-4/IL-13 blockade using Dupilumab therapy. Accomplishment of these Specific Aims will contribute to novel and important advances in our understanding of mechanisms of host skin defense and paradigm-shifting treatments of AD. The establishment of this ADRN-LC will also provide budgetary and scientific resources for the Systems Biology of Early Atopy Birth Cohort study that is under development by the Consortium for Food Allergy Research (CoFAR)."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"OREGON HEALTH & SCIENCE UNIVERSITY","value":999999,"savings":901810,"link":null,"description":"OVERALL ABSTRACT The Oregon National Primate Research Center (ONPRC), located on the West Campus of Oregon Health & Science University (OHSU), requests funds to renew grant P51--OD011092 for the next five-year period (May 1, 2024--April 30, 2029). Currently, in its 63rd year of operation, the ONPRC has served a broad range of local, regional, and national investigators performing biomedical research in nonhuman primate (NHP) models with the goal of improving human health. The goals for the next funding period are reflected in the following Specific Aims: 1) Conduct state-of-the-art research in a clinically relevant animal model that advances human health through understanding the causes of disease and the development of preventions, treatments and cures; 2) Provide exceptional NHP expertise and services to researchers at the local, regional, and national levels to advance translational research programs; 3) Pursue the highest standards of humane and responsible animal care; and 4) Mentor and train the next generation of translational NHP researchers and educate the public about the importance of biomedical research. To accomplish these aims, support is requested in seven broad areas. These areas are: 1) Administration, which provides the administrative and service support required for all aspects of the ONPRC (Governance, Director’s Office, Business Services, Facilities, Improvements and Modernization, Information Systems, Research Library, and Environmental Health & Safety); (2) Animal Services (Behavioral Services; Clinical Medicine; Compliance, Education and Training; Operations; Pathology Services; Surgical Services; Resources & Logistics; as well as the NHP Resources that include Aging, Infectious Disease, Obese, and Precision Medicine); (3) Core Support Services (Research Cores that included Assisted Reproductive Technologies, Bioinformatics & Biostatistics, Endocrine Technologies, Flow Cytometry, Integrated Pathology, Magnetic Resonance Imaging (MRI), Molecular Virology, and Primate Genetics); (4) Scientific Units, including support for Scientific Divisions (Metabolic Health & Disease, Genetics, Neuroscience, Pathobiology & Immunology, and Reproductive & Developmental Sciences); (5) Pilot Research Program; (6) Outreach and Community Engagement; and (7) NPRC Consortium--Based Activities. ONPRC’s overarching goal is to develop, study, and share NHP models that can inform the causes of human diseases, leading to better preventions, treatments, and cures. The ONPRC achieves this goal by supporting translational research and expertise in models that are provided locally, regionally, and nationally on a collaborative basis. ONPRC research support and accomplishments consistently ‘top the list’ relative to other research departments, centers, and institutes at the host institution, OHSU. Thus, the University recognizes the importance of ONPRC and has pledged to continue to support its programmatic and infrastructure development."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"PURDUE UNIVERSITY","value":3099128,"savings":351182,"link":null,"description":"NOVEL DELIVERY PLATFORM AND ANTIGEN DESIGN FOR AN EFFECTIVE COVID-19 VACCINE"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"REGENTS OF THE UNIVERSITY OF COLORADO, THE","value":726000,"savings":548140,"link":null,"description":"A TUNABLE NANOPHAGE PLATFORM FOR VACCINE DEVELOPMENT - PROJECT SUMMARY NEWLY EMERGING AND LONG-STANDING INFECTIOUS CHALLENGES, INCLUDING ARBOVIRUSES, EBOLA VIRUS AND PANDEMIC CORONAVIRUSES (COVS), AMONG OTHERS, POSE SERIOUS PUBLIC HEALTH CONCERNS. ADDITIONALLY, THE POTENTIAL USE OF BIOLOGICAL AGENTS AS WEAPONS OF MASS DESTRUCTION POSES AN ONGOING THREAT TO HUMANITY. ALL OF THESE ISSUES HAVE IN COMMON THE NEED FOR DEVELOPMENT STRATEGIES THAT ALLOW FOR THE RAPID DESIGN, SCREENING AND FORMULATION OF POTENTIAL VACCINE CANDIDATES. WE HAVE DEVELOPED A “DESIGNER NANOPARTICLE” PLATFORM BASED ON Λ PHAGE-LIKE PARTICLES, OR NANOPHAGES (NPS), THAT CAN DISPLAY MULTIPLE ANTIGENIC BIOMOLECULES ALONE AND IN COMBINATION IN RIGOROUSLY DEFINED RATIOS. THE NPS CAN BE RAPIDLY MODIFIED TO SCREEN AND EVALUATE POTENTIAL VACCINE CANDIDATES AGAINST NEWLY EMERGING THREATS. HEREIN WE PROPOSE TO DEVELOP TOOLS AND TECHNOLOGIES FOR RAPID SCREENING OF MULTIVALENT VACCINE CANDIDATES EFFECTIVE FOR CURRENT AND EMERGING SARS-COVS AND PRE- EMERGENT SARS-LIKE COVS. WE WILL ENGINEER “SECOND GENERATION” NANOPHAGES (NPS) THAT DISPLAY THE SPIKE RECEPTOR BINDING DOMAIN (RBD) FOR THESE PATHOGENS, THE PRIMARY TARGET OF NEUTRALIZING ANTIBODY (AB) RESPONSES. PHYSIOCHEMICAL AND STRUCTURAL CHARACTERIZATION OF THE PREPARATIONS WILL BE EMPLOYED TO ENSURE THAT THEY POSSESS PROPERTIES THAT ARE APPROPRIATE FOR A PHARMACEUTICAL PREPARATION. WE WILL ALSO EMPLOY A NOVEL ATOMIC LAYER DEPOSITION TECHNOLOGY TO GENERATE THERMOSTABLE, TIMED-RELEASE, SINGLE-SHOT VACCINE FORMULATIONS THAT REDUCE OR ELIMINATE ONEROUS “COLD-CHAIN” REQUIREMENTS FOR THEIR DISTRIBUTION. WE FURTHER PROPOSE TO DETERMINE THE IMMUNOGENICITY AND PROTECTIVE CAPACITY OF MOSAIC NPS ENGINEERED TO SIMULTANEOUSLY DISPLAY MULTIPLE ANTIGENS. THESE STUDIES WILL IDENTIFY VACCINE CANDIDATES THAT ELICIT POTENT, DURABLE, AND BROAD NEUTRALIZING AB AND T CELL RESPONSES AND PROTECTIVE IMMUNITY AGAINST SARS-COV-2 VARIANTS AND PRE-EMERGENT SARS-LIKE BAT COVS. IN ADDITION TO DEVELOPING THIS POWERFUL PLATFORM AND IMPLEMENTING NOVEL FORMULATION STRATEGIES, THESE STUDIES WILL HELP DEFINE MECHANISMS OF IMMUNOGENICITY AND DEVELOP A PLATFORM FOR THE RAPID ENGINEERING OF VACCINE CANDIDATES FOR EXISTING AND UNTOWARD EMERGING BIOLOGICAL THREATS. IN SUM, THIS APPLICATION SEEKS TO PROVIDE COMPELLING EVIDENCE THAT THE  NANOPHAGE SYSTEM PROVIDES A PLATFORM FOR FACILE AND RAPID GENERATION, AND FORMULATION OF HIGHLY ACTIVE MULTI-ANTIGEN PRESENTING VACCINES."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"RESEARCH TRIANGLE INSTITUTE","value":37709210,"savings":18302229,"link":null,"description":"ACTIV INTEGRATION OF HOST-TARGETING THERAPIES FOR COVID-19 ADMINISTRATIVE COORDINATING CENTER - RTI INTERNATIONAL IS PLEASED TO PROVIDE THIS APPLICATION AS REQUESTED BY THE RESEARCH OPPORTUNITIES ANNOUNCEMENT OTA-20-011 ACTIV INTEGRATION OF HOST-TARGETING THERAPIES FOR COVID-19 FOR THE ROLE OF ADMINISTRATIVE COORDINATING CENTER (ACC). THE TITLE OF OUR APPLICATION IS ACTIV INTEGRATION OF HOST-TARGETING THERAPIES FOR COVID-19 ADMINISTRATIVE COORDINATING CENTER. THE INTEGRATION OF HOST-TARGETING THERAPIES FOR COVID-19 PROGRAM AIMS TO IDENTIFY COVID-19 INTERVENTIONS RELEVANT TO HEART, LUNG, BLOOD, AND CARDIOVASCULAR OUTCOMES THAT CONTRIBUTE TO THE SCIENTIFIC KNOWLEDGE BASE ARE LIKELY TO INFORM CLINICAL PRACTICE. THIS PROGRAM WILL RAPIDLY AND EFFICIENTLY CONDUCT ADAPTIVE PLATFORM TRIALS VIA A COORDINATED EFFORT OF DATA COORDINATING CENTERS AND CLINICAL SITES FROM EXISTING CLINICAL STUDY NETWORKS. THE ACC IS A CRITICAL COMPONENT OF THE PROGRAM. WE WILL COORDINATE WITH NHLBI TO ENSURE COLLABORATION AMONG NETWORKS INCLUDING THE USE OF STANDARDIZED APPROACHES IN CLINICAL TRIAL DESIGN AND CONDUCT, DATA COLLECTION AND VALIDATION, AND STATISTICAL ANALYSIS SUCH THAT STUDIES ARE LAUNCHED, IMPLEMENTED AND ANALYZED SWIFTLY; AND STUDY FINDINGS ARE SCIENTIFICALLY SOUND AND MEET REGULATORY NEEDS FOR MEDICAL THERAPY DEVELOPMENT. AS THE ACC, WE WILL ALSO SERVE THE VITAL ROLE OF FACILITATING COMMUNICATION AND INFORMATION SHARING AMONG ALL RELEVANT STAKE HOLDERS AND HELPING NHLBI IN TRACKING STUDY-SPECIFIC AND PROGRAM-WIDE MILESTONES. SONIA THOMAS, DRPH, WILL LEAD THE ACC AS PRINCIPAL INVESTIGATOR. SHE IS AN EXPERIENCED CC PI AND STATISTICIAN WITH 25 YEARS OF EXPERIENCE IN THE DESIGN, IMPLEMENTATION, AND ANALYSIS OF MULTICENTER NIHAND INDUSTRY-SPONSORED PHASE 2-4 CLINICAL TRIALS OF DRUGS, BIOLOGICS, DEVICES, SURGICAL AND BEHAVIORAL INTERVENTIONS IN MORE THAN A DOZEN THERAPEUTIC INDICATIONS. DR. THOMAS WILL BE SUPPORTED BY TRACY NOLEN, DRPH AS ALTERNATE PI, AN EXPERIENCED CONSORTIUM AND CC PI AND CLINICAL TRIAL STATISTICIAN, AND SUBJECT MATTER EXPERTS STEVE NISSEN, MD, CLEVELAND CLINICAL CHIEF ACADEMIC OFFICER, HEART AND VASCULAR INSTITUTE, SHANNON CARSON, MD, UNIV. OF NORTH CAROLINA CHIEF OF PULMONARY AND CRITICAL CARE MEDICINE, AND ANASTASIA IVANOVA, PHD, UNIV. OF NORTH CAROLINA PROFESSOR OF BIOSTATISTICS UNDER DR THOMAS’S DIRECTION, OUR TEAM WILL LEAD, SUPPORT, AND COLLABORATE WITH PROGRAM NETWORKS THROUGH ORGANIZATION INTO 6 ACC CORES: PROGRAM OPERATIONS, SCIENTIFIC LEADERSHIP AND PRIORITIZATION, INFORMATICS, DATA STANDARDS, STUDY DESIGN, IMPLEMENTATION, & ANALYSIS, AND REGULATORY AND QA. WE HAVE IDENTIFIED MILESTONES FOR THE ESSENTIAL ACTIVITIES OF THE ACC WITHIN EACH OF THESE 6 CORES WITH A DETAILED FOCUS ON THE ACTIVITIES IN THE FIRST 6 MONTHS AS ACTIVITIES COMPLETED DURING THIS TIME ARE MOST IMPORTANT FOR ENSURING THE COORDINATED, EXPEDITED AND EFFICIENT LAUNCH OF THIS PROGRAM. DR. THOMAS, OUR SUBJECT MATTER EXPERTS, SENIOR STATISTICAL SCIENTISTS, AND MANY OF THE CORE LEADS HAVE SUBSTANTIAL EXPERIENCE WITH NHLBI AND THUS UNDERSTAND THE NEEDS AND PRIORITIES OF THE INSTITUTE AND WILL USE THIS KNOWLEDGE TO BETTER COLLABORATE WITH NHLBI AND FURTHER SPEED UP THE LAUNCH OF THIS PROGRAM. WE ARE WILLING TO COLLABORATE WITH ALL INVOLVED ENTITIES AS PART OF THE OVERARCHING TRANS-NIH ACTIV PROGRAM AS IT EVOLVES. WE RECOGNIZE AND ANTICIPATE THAT SWIFT ADAPTATION WILL BE REQUIRED TO RAPIDLY RESPOND TO THE URGENT CLINICAL RESEARCH NEEDS TO ADDRESS THE COVID-19 PANDEMIC. RTI IS UNIQUELY AND SUBSTANTIALLY QUALIFIED FOR THE ACC. WE WILL USE OUR TEAM’S BROAD EXPERIENCE FROM MANY COMPLEX COORDINATING CENTER PROJECTS TO ANTICIPATE THE NEEDS FOR THIS PROGRAM AND “HIT THE GROUND RUNNING”. PROVEN INFORMATICS TECHNOLOGY IN USE BY EXISTING NIH PROGRAMS WILL BE SWIFTLY MODIFIED BY OUR ANALYSTS FOR SPEEDY DEPLOYMENT OF COMMUNICATIONS PLATFORMS. OUR ORGANIZATIONAL SIZE AND FLEXIBILITY WILL ALLOW US TO RAMP UP QUICKLY AND MODIFY PERSONNEL RESOURCES FLEXIBLY. LASTLY, RTI"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"ROCKEFELLER UNIVERSITY","value":7019416,"savings":6267829,"link":null,"description":"Project Summary/Abstract Rockefeller University is a unique institution: with only 70 Heads of Laboratories, the faculty have received 3 Nobel prizes in Medicine in the last 10 years and 5 (plus 1 in chemistry) in the last 21 years, along with appointment of 18 faculty as HHMI investigators and 29 to membership in the National Academy of Sciences. Rockefeller faculty have played an outsized role in contributions to foundational discoveries in virology and infectious disease, both historically and presently. Recognizing the importance of the current pandemic, over the past two years, a dozen research groups at Rockefeller have joined the research efforts focused on pandemic threat viruses, with numerous grants supporting the work and over 50 peer-reviewed publications to date. Rockefeller labs have made seminal contributions identifying the spectrum of neutralizing antibodies to the SARS-CoV-2 spike protein, the impact of variants on neutralization, and characterizing the atomic- resolution binding of antibodies to spike protein. Collectively, Rockefeller laboratories are working on Alphaviruses (e.g., Sindbis, chikungunya viruses), Flaviviruses (e.g., yellow fever, Zika, West Nile, Powassan viruses), Hepaciviruses (hepatitis C virus, Norway rat hepacivirus), Hepadnaviruses (hepatitis B virus), Orthomyxoviruses (influenza), Coronaviruses (SARS-CoV-2 and other human coronaviruses) and retroviruses including HIV-1. Many of the viruses under study, including chikungunya, yellow fever, West Nile, Powassan, and SARS-CoV-2, are classified as Risk Group 3 (RG3) pathogens, requiring BSL3 containment facilities and practices. Moreover, some research at Rockefeller includes the generation of replicons and chimeric (VSV- based) viruses whose stability and safety should be established under BSL3 conditions prior to use at lower biosafety containment levels. This project seeks to enhance and expand space and support for both in vivo and in vitro research. Specific aim 1 is to increase the Rockefeller University’s BSL3 capacities to meet the scientific needs by establishing a new BSL3 facility in an existing laboratory building. Specific aim 2 is to equip and enhance the new facility and the BSL3/ABSL3 facilities that already exist at the University. To achieve these aims, an extremely experienced team of personnel at Rockefeller propose to: establish a new multiple- investigator BSL3 facility; add equipment to the existing single-PI BSL3 facility; replace an existing autoclave and add an incremental autoclave in the ABSL3; and modernize the supporting infrastructure in the ABSL3."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"ROCKEFELLER UNIVERSITY","value":4259011,"savings":2400853,"link":null,"description":"BROAD NEUTRALIZATION OF PANDEMIC THREAT CORONAVIRUSES - ABSTRACT-OVERALL  THE RECURRENT EMERGENCE OF CORONAVIRUSES FROM ANIMAL RESERVOIRS, AND THE RESULTING COVID19 PANDEMIC, NECESSITATES THE DEVELOPMENT OF INTERVENTIONS THAT CAN TARGET DIVERSE PANDEMIC-THREAT CORONAVIRUSES. VACCINES ARE AMONG THE MOST POWERFUL MEANS FOR MITIGATING VIRAL EPIDEMICS BUT REQUIRE SIGNIFICANT BREADTH TO MAXIMIZE THE PROBABILITY OF EFFECTIVENESS AGAINST UNKNOWN VIRAL THREATS. CURRENTLY, FIRST GENERATION VACCINES ARE BEING DEPLOYED TO COMBAT SARS-COV-2, BUT THEIR EFFECTIVENESS AGAINST EMERGENT SARS-COV-2 VARIANTS AND, IMPORTANTLY, AGAINST OTHER POTENTIAL ZOONOTIC CORONAVIRUSES IS UNKNOWN. THIS PROGRAM WILL FOCUS ON NEUTRALIZING ANTIBODIES AS A DEMONSTRATED AND KEY COMPONENT OF PROTECTIVE IMMUNE RESPONSES. THE PROGRAM WILL IMPROVE PREPAREDNESS AGAINST CORONAVIRUSES, EMPLOYING A PROGRESSIVE MULTISTEP APPROACH TO INCREASE THE BREADTH OF VACCINE PROTECTION. A KEY COMPONENT OF THE RESEARCH WILL BE TO COMPREHEND HOW NEUTRALIZING ANTIBODY RESPONSES, ELICITED IN HUMANS FOLLOWING NATURAL INFECTION OR VACCINATION, TARGET THE SARS-COV-2 ENVELOPE SPIKE AND HOW ANTIBODY EVOLUTION LEADS TO INCREASED POTENCY AND BREADTH. THE IDENTIFICATION AND CHARACTERIZATION OF EPITOPES TARGETED BY SARS-COV-2 NEUTRALIZING ANTIBODIES, USING MULTIPLE APPROACHES, WILL GUIDE THE DESIGN OF IMMUNOGENS THAT AIM TO ELICIT NEUTRALIZING ANTIBODIES TARGETING AS DIVERSE A SPECTRUM OF CORONAVIRUSES AS POSSIBLE. SEVERAL IMMUNOGENS AND DELIVERY STRATEGIES WILL BE TESTED IN MICE AND HAMSTERS THAT WILL BE CHALLENGED WITH AUTHENTIC SARS-COV-2 OR A PANOPLY OF NEWLY DEVELOPED CHALLENGE MODELS INCORPORATING DIVERGENT CORONAVIRUS SPIKE PROTEINS. ANTIBODIES ELICITED IN THESE ANIMALS WILL BE ANALYZED AND COMPARED WITH THOSE FOUND IN SARS-COV-2 IMMUNIZED HUMANS AND IMMUNOGENS PROGRESSIVELY REFINED AND DOWN-SELECTED WITH THE GOAL OF PERFORMING VACCINE-CHALLENGE EXPERIMENTS IN NONHUMAN PRIMATES WITH THE MOST PROMISING CANDIDATES. THE EXPERTISE OF EACH PARTICIPATING TEAM IS HIGHLY COMPLEMENTARY AND THE PROGRAM WILL CAPITALIZE AND BUILD ON THE ALREADY EXISTING SCIENTIFIC SYNERGY TO ENSURE THE EFFICIENT AND TIMELY COMPLETION OF THE GOALS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"ROCKEFELLER UNIVERSITY","value":6423268,"savings":345035,"link":null,"description":"BROAD NEUTRALIZATION OF PANDEMIC THREAT CORONAVIRUSES - ABSTRACT-OVERALL  THE RECURRENT EMERGENCE OF CORONAVIRUSES FROM ANIMAL RESERVOIRS, AND THE RESULTING COVID19 PANDEMIC, NECESSITATES THE DEVELOPMENT OF INTERVENTIONS THAT CAN TARGET DIVERSE PANDEMIC-THREAT CORONAVIRUSES. VACCINES ARE AMONG THE MOST POWERFUL MEANS FOR MITIGATING VIRAL EPIDEMICS BUT REQUIRE SIGNIFICANT BREADTH TO MAXIMIZE THE PROBABILITY OF EFFECTIVENESS AGAINST UNKNOWN VIRAL THREATS. CURRENTLY, FIRST GENERATION VACCINES ARE BEING DEPLOYED TO COMBAT SARS-COV-2, BUT THEIR EFFECTIVENESS AGAINST EMERGENT SARS-COV-2 VARIANTS AND, IMPORTANTLY, AGAINST OTHER POTENTIAL ZOONOTIC CORONAVIRUSES IS UNKNOWN. THIS PROGRAM WILL FOCUS ON NEUTRALIZING ANTIBODIES AS A DEMONSTRATED AND KEY COMPONENT OF PROTECTIVE IMMUNE RESPONSES. THE PROGRAM WILL IMPROVE PREPAREDNESS AGAINST CORONAVIRUSES, EMPLOYING A PROGRESSIVE MULTISTEP APPROACH TO INCREASE THE BREADTH OF VACCINE PROTECTION. A KEY COMPONENT OF THE RESEARCH WILL BE TO COMPREHEND HOW NEUTRALIZING ANTIBODY RESPONSES, ELICITED IN HUMANS FOLLOWING NATURAL INFECTION OR VACCINATION, TARGET THE SARS-COV-2 ENVELOPE SPIKE AND HOW ANTIBODY EVOLUTION LEADS TO INCREASED POTENCY AND BREADTH. THE IDENTIFICATION AND CHARACTERIZATION OF EPITOPES TARGETED BY SARS-COV-2 NEUTRALIZING ANTIBODIES, USING MULTIPLE APPROACHES, WILL GUIDE THE DESIGN OF IMMUNOGENS THAT AIM TO ELICIT NEUTRALIZING ANTIBODIES TARGETING AS DIVERSE A SPECTRUM OF CORONAVIRUSES AS POSSIBLE. SEVERAL IMMUNOGENS AND DELIVERY STRATEGIES WILL BE TESTED IN MICE AND HAMSTERS THAT WILL BE CHALLENGED WITH AUTHENTIC SARS-COV-2 OR A PANOPLY OF NEWLY DEVELOPED CHALLENGE MODELS INCORPORATING DIVERGENT CORONAVIRUS SPIKE PROTEINS. ANTIBODIES ELICITED IN THESE ANIMALS WILL BE ANALYZED AND COMPARED WITH THOSE FOUND IN SARS-COV-2 IMMUNIZED HUMANS AND IMMUNOGENS PROGRESSIVELY REFINED AND DOWN-SELECTED WITH THE GOAL OF PERFORMING VACCINE-CHALLENGE EXPERIMENTS IN NONHUMAN PRIMATES WITH THE MOST PROMISING CANDIDATES. THE EXPERTISE OF EACH PARTICIPATING TEAM IS HIGHLY COMPLEMENTARY AND THE PROGRAM WILL CAPITALIZE AND BUILD ON THE ALREADY EXISTING SCIENTIFIC SYNERGY TO ENSURE THE EFFICIENT AND TIMELY COMPLETION OF THE GOALS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY","value":1864117,"savings":290155,"link":null,"description":"DEVELOPMENT OF DUAL INHIBITORS TARGETING THE VIRAL MAIN PROTEASE AND THE HOST CATHEPSIN L AS SARS-COV-2 ANTIVIRALS - PROJECT SUMMARY  THE SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2), ALSO CALLED NOVEL CORONAVIRUS 2019 (NCOV-19), STARTED TO CIRCULATE AMONG HUMANS AROUND DECEMBER 2019, AND IT IS NOW WIDESPREAD AS A GLOBAL PANDEMIC. THERE IS NO VACCINE OR ANTIVIRAL AVAILABLE FOR SARS-COV-2. IN THIS GRANT, WE PROPOSE TO DEVELOP DUAL INHIBITORS TARGETING VIRAL MAIN PROTEASE AND CATHEPSIN L AS SARS-COV-2 ANTIVIRALS. USING THE FRET-BASED ENZYMATIC ASSAY, WE RECENTLY IDENTIFIED SEVERAL INHIBITORS INCLUDING BOCEPREVIR, GC-376, AND CALPAIN INHIBITORS II AND XII, THAT HAVE POTENT ACTIVITY WITH SINGLE-DIGIT TO SUBMICROMOLAR IC50 VALUES IN THE ENZYMATIC ASSAY. SIGNIFICANTLY, ALL FOUR COMPOUNDS INHIBIT INFECTIOUS SARS-COV-2 REPLICATION IN CELL CULTURE WITH EC50 VALUES RANGING FROM 0.5 TO 3.4 ÎœM. OVERALL, THE COMPOUNDS IDENTIFIED PROVIDE PROMISING STARTING POINTS FOR THE FURTHER DEVELOPMENT OF SARS-COV-2 THERAPEUTICS. OUR DISCOVERY OF CALPAIN INHIBITOR II AS A POTENT INHIBITOR AGAINST SARS-COV-2 IS INNOVATIVE AS IT SUGGESTS IT MIGHT BE FEASIBLE TO DEVELOP SARS-COV-2 ANTIVIRALS BY SIMULTANEOUSLY TARGETING BOTH VIRAL MPRO AND HOST CATHEPSIN L, BOTH OF WHICH ARE ESSENTIAL FOR VIRAL REPLICATION. COMPARED TO RECENTLY REPORTED MPRO INHIBITORS, THE HITS IDENTIFIED FROM OUR STUDY REPRESENT THE MOST POTENT AND SELECTIVE DRUG CANDIDATES WITH A NOVEL MECHANISM OF ACTION, THEREFORE WARRANTING FURTHER DEVELOPMENT.  GIVEN OUR ENCOURAGING PRELIMINARY DATA, WE PROPOSE TO OPTIMIZE DUAL INHIBITORS AS SARS-COV-2 ANTIVIRALS. THE OBJECTIVE OF THIS PROPOSAL IS TO DEVELOP DUAL INHIBITORS AS POTENT SARS-COV-2 ANTIVIRALS WITH HIGH POTENCY, SELECTIVITY, FAVORABLE PHARMACOKINETIC PROPERTIES, AS WELL AS BROAD-SPECTRUM ANTIVIRAL ACTIVITY AGAINST CLOSELY RELATED CORONAVIRUSES SUCH AS SARS AND MIDDLE EAST RESPIRATORY SYNDROME (MERS) CORONAVIRUSES.  OUR GOALS OF THIS GRANT ARE TO IDENTIFY ADDITIONAL DUAL INHIBITORS THROUGH BOTH HIGH-THROUGHPUT SCREENING AND STRUCTURE-BASED LEAD OPTIMIZATION OF OUR RECENTLY IDENTIFIED DUAL INHIBITORS. BY TARGETING THE SARS-COV-2 MPRO, THE EXPECTED OUTCOMES OF THE PROPOSED RESEARCH ARE BROAD-ACTING CORONAVIRUS ANTIVIRALS WITH A CONFIRMED MECHANISM OF ACTION, A HIGH SELECTIVITY INDEX, AND FAVORABLE IN VITRO PHARMACOKINETIC PROPERTIES THAT ARE READY FOR IN VIVO ANTIVIRAL EFFICACY TESTING IN RELEVANT ANIMAL MODELS. OVERALL, THIS GRANT IS BASED ON STRONG PRELIMINARY DATA AND OUR EXPERTISE IN DEVELOPING ANTIVIRALS TARGETING CYSTEINE PROTEASES."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"SCRIPPS RESEARCH INSTITUTE","value":67624156,"savings":11023485,"link":null,"description":"CENTER FOR ANTIVIRAL MEDICINES & PANDEMIC PREPAREDNESS (CAMPP) - SUMMARY THE ONGOING COVID-19 PANDEMIC HAS BROUGHT TO LIGHT AN URGENT NEED TO ENHANCE THE THERAPEUTIC PREPAREDNESS FOR FUTURE VIRAL OUTBREAKS AND PANDEMICS. THE OVERARCHING GOAL OF THE “CENTER FOR ANTIVIRAL MEDICINES & PANDEMIC PREPAREDNESS” (CAMPP) IS THUS TO DEVELOP NOVEL STRATEGIES AND ENHANCE THE DRUG DISCOVERY PIPELINES FOR DIRECT-ACTING ANTIVIRALS AGAINST RNA VIRUSES OF PANDEMIC CONCERN. THE SPECIFIC FOCUS OF CAMPP WILL BE TO DEVELOP ANTIVIRALS AGAINST CORONAVIRUSES SARS-COV-2 (SCV2), SARS AND MERS; FLAVIVIRUSES INCLUDING ZIKA, WEST NILE AND DENGUE VIRUS; AND HEMORRHAGIC FEVER VIRUSES INCLUDING THE FILOVIRUS EBOLA, AND BUNYAVIRUSES SEVERE FEVER WITH THROMBOCYTOPENIA SYNDROME VIRUS AND LASSA VIRUS. INFECTION BY ANY OF THESE AGENTS HAS THE POTENTIAL TO CAUSE SEVERE HUMAN DISEASE WITH SIGNIFICANT MORTALITY RATES AND CURRENT OPTIONS FOR ANTIVIRAL TREATMENTS ARE LIMITED. THE ANTIVIRAL DRUG REMDESIVIR AND SEVERAL MONOCLONAL ANTIBODY TREATMENTS HAVE RECEIVED EMERGENCY USE AUTHORIZATION (EUA) FOR TREATMENT OF COVID-19, AND THE POLYMERASE INHIBITOR MOLNUPIRAVIR BY MERCK IS EXPECTED TO BE GRANTED EUA IN THE NEAR FUTURE. MONOCLONAL ANTIBODIES ARE ALSO AVAILABLE TO TREAT EBOLA VIRUS INFECTION, HOWEVER, NONE OF THESE DRUGS CAN BE ADMINISTERED ORALLY, POSING ADDITIONAL CHALLENGES IN TREATING EARLY INFECTION. THERE ARE NO APPROVED TREATMENTS FOR THE CAMPP FLAVIVIRUSES AND HEMORRHAGIC FEVER VIRUSES. TOWARD THIS END, WE HAVE ASSEMBLED A WORLD CLASS MULTIDISCIPLINARY TEAM OF INVESTIGATORS WITH EXPERTISE IN VIROLOGY OF RELEVANT VIRUSES, STRUCTURAL AND COMPUTATIONAL BIOLOGY, CHEMOPROTEOMICS, PHARMACOLOGY AND ORGANOID/ANIMAL MODELS, WHO WILL WORK CLOSELY WITH THE DRUG DEVELOPMENT EXPERTS AT THE DRUG DISCOVERY DIVISION OF THE SCRIPPS RESEARCH INSTITUTE, CALIBR, TO FURTHER THE DEVELOPMENT OF FOUR MAJOR CLASSES OF PROMISING ASSETS IN OUR DRUG DISCOVERY PIPELINE. FIRST, WE PROPOSE TO DEVELOP A POTENTIALLY BEST-IN-CLASS, ORALLY BIOAVAILABLE CORONAVIRUS PROTEASE (CLPRO) INHIBITOR FOR CORONAVIRUSES INCLUDING SCV2, FROM A LATE-STAGE DRUG ASSET UNDERGOING ADME OPTIMIZATION THAT IS EXPECTED TO ENTER IND-ENABLING STUDIES WITHIN THE NEXT THREE YEARS. SECOND, WE WILL IDENTIFY AND OPTIMIZE RNA POLYMERASE INHIBITORS FOR SCV2 AND OTHER CAMPP VIRUSES, WITH THE GOAL OF REACHING IND-ENABLING STUDIES WITHIN THE NEXT FOUR YEARS. THE THIRD FOCUS OF OUR PROPOSAL IS TO DEVELOP ANTIVIRALS AGAINST OTHER ‘DRUGGABLE’ PROTEINS ENCODED BY SCV2 AND ADDITIONAL VIRUSES POSING A PANDEMIC THREAT; THESE ASSETS INCLUDE INHIBITORS OF SCV2 HELICASE, E-PROTEIN ENCODED ION CHANNEL ACTIVITY, ENTRY AND FUSION ACTIVITIES, AND NUCLEOCAPSID, WITH THE GOAL OF OBTAINING IN VIVO PROOF-OF-CONCEPT FOR A SUBSET OF THESE MID-STAGE ASSETS. FINALLY, WE PROPOSE TO TARGET TRADITIONALLY CONSIDERED ‘UNDRUGGABLE’ NON-ENZYMATIC PROTEINS INCLUDING SCV2 AND FLAVIVIRAL STRUCTURAL PROTEINS AS WELL AS RNA STRUCTURE, TO DEVELOP NOVEL STRATEGIES FOR ANTIVIRAL DRUG DEVELOPMENT. CAMPP PROVIDES A HIGHLY INTEGRATED INFRASTRUCTURE OF INVESTIGATORS, EXPERTISE AND EXTERNAL PHARMACEUTICAL AND FOUNDING PARTNERS THAT WILL ENSURE THE CENTER’S SUCCESS IN ACHIEVING OUR GOALS AND NAVIGATING CHALLENGES OF THE DRUG DISCOVERY PROCESS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"SCRIPPS RESEARCH INSTITUTE","value":3869562,"savings":404009,"link":null,"description":"IMPROVING THE SCRIPPS RESEARCH INSTITUTE BSL3 CAPABILITIES TO COMBAT VIRUSES OF PANDEMIC CONCERN - PROJECT SUMMARY/ABSTRACT THE GOAL OF THE APPLICATION “IMPROVING THE SCRIPPS RESEARCH INSTITUTE BSL3 CAPABILITIES TO COMBAT VIRUSES OF PANDEMIC CONCERN” IS TO RENOVATE AND UPGRADE THE SCRIPPS RESEARCH INSTITUTE (TSRI) CURRENT ABSL3 AND BSL3 FACILITIES. THIS WILL ENHANCE TSRI RESEARCH CAPABILITIES TO COMBAT RNA VIRUSES OF PANDEMIC POTENTIAL. TSRI HAS ~ 2,000 SF DEDICATED TO ABSL3 AND ~ 1,500 SF DEDICATED TO BSL3. CURRENTLY, THESE FACILITIES SUPPORT RESEARCH PROJECTS FROM EIGHT TSRI FACULTY WHOSE COMBINED AREAS OF EXPERTISE COVER RESEARCH ON RNA VIRUSES OF PANDEMIC POTENTIAL, INCLUDING BUNYAVIRALES, CORONAVIRIDAE, FLAVIVIRIDAE, FILOVIRIDAE AND TOGAVIRIDAE. IN ADDITION, THE FACILITIES ARE SUPPORTING SEVERAL PROJECTS SPONSORED BY PHARMACEUTICAL COMPANIES. THE SPECIFIC STUDIES HAVE STRONG TRANSLATIONAL COMPONENTS AIMED AT DEVELOPING ANTIVIRAL DRUGS AND IMMUNOTHERAPEUTICS AGAINST THESE RNA VIRUSES. TSRI ABSL3 AND BSL3 SUITES, LOCATED IN THE MOLECULAR BIOLOGY BUILDING (MBB), HAVE BEEN OPERATING 24/7 SINCE THE LAST RENOVATIONS IN 2004. THE EXISTING MECHANICAL SYSTEMS HAVE BEEN MAINTAINED BEYOND ASHREA EQUIPMENT LIFE EXPECTANCY FOR THE LA JOLLA, CA. COASTAL CLIMATE. IN ADDITION, THE ORIGINAL DESIGN FROM 1985-87 HAS RESULTED IN UNDERUTILIZATION OF ~160 SF IN THE ABSL3 AND ~400 SF IN THE BSL3. TO CORRECT THESE DEFICIENCIES, TSRI HAS COMPLETED A CONCEPTUAL DESIGN WITH FPBA ARCHITECTS & TK1SC MECHANICAL ENGINEERS. THIS PLAN INCLUDES REPLACING THE AGING HVAC SYSTEMS OF THE ABSL3 AND BSL3 SPACE TO INCREASE AIRFLOW CAPACITY WITH N+1 REDUNDANCY AND UPDATE THE HEPA FILTRATION SYSTEM OF THE ABSL3. IN ADDITION, THE PROJECT WILL MODERNIZE THE BIOCONTAINMENT SUITES BY INCREASING HOLDING CAPACITY (ABSL3), CREATING A SELECT AGENT ISOLATION ROOM (BSL3), AND INSTALLING A NEW STERILIZER (ABSL3). THE CURRENT ABSL3/BSL3 FACILITIES LACK IMAGING, CELL SORTING, AND SINGLE CELL ANALYSIS CAPABILITIES. TO REMEDY THESE DEFICIENCIES, WE PROPOSE ADDING TO THE FACILITY THE EVOSTM IMAGING SYSTEM, THE SH800S CELL SORTER AND THE CHROMIUM IX SYSTEM. THESE IMPROVEMENTS WILL HELP TO ADDRESS THE INCREASING DEMANDS BY TSRI FACULTY FOR ABSL3/BSL3 SPACE, TIME AND IMPROVED FUNCTIONAL CAPABILITIES, WHILE ENSURING THE HIGHEST LEVEL OF SAFETY DURING DAILY OPERATIONS OF THE FACILITY. MOREOVER, RESEARCH ACTIVITIES PROPOSED UNDER THE ANTIVIRAL PROGRAM FOR PANDEMICS (APP) U19AI171443 AVIDD GRANT APPLICATION, WILL GREATLY BENEFIT FROM THE PROPOSED IMPROVEMENTS TO THE CURRENT TSRI ABSL3 AND BSL3 FACILITIES. THE PROJECT WILL BE MANAGED BY A WELL-INTEGRATED AND HIGHLY QUALIFIED TEAM, INCLUDING LEADERS FROM FACILITIES CONSTRUCTION AND ENGINEERING, THE INSTITUTIONAL ANIMAL PROGRAM AND RESOURCES, EHS AND BIOSAFETY, THE EXECUTIVE VP OFFICE, AND INVESTIGATORS DIRECTLY INVOLVED IN ABSL3/BSL3 RESEARCH ACTIVITIES. IN ADDITION, THE APPLICATION HAS THE UNWAVERING SUPPORT OF THE TSRI LEADERSHIP."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"SEATTLE CHILDREN`S HOSPITAL","value":2918031,"savings":758981,"link":null,"description":"VIRAL AND IMMUNE KINETICS IN RHINOVIRUS INFECTION FOLLOWING HEMATOPOIETIC CELL TRANSPLANTATION"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH","value":67673902,"savings":22127008,"link":null,"description":"AI-DRIVEN STRUCTURE-ENABLED ANTIVIRAL PLATFORM (ASAP) - PROJECT SUMMARY/ABSTRACT - OVERALL SARS-COV-2 CONTINUES TO CAUSE SEVERE MORBIDITY AND MORTALITY IN THE ONGOING PANDEMIC. FUTURE RNA VIRUS EPIDEMICS AND PANDEMICS ARE INEVITABLE. NEW CLINICAL-TRIAL-READY ANTIVIRALS ARE URGENTLY NEEDED RNA VIRUSES OF PANDEMIC POTENTIAL. COVID-19 HAS FURTHER UNDERSCORED THE NEED FOR EARLY, GLOBAL ACCESS TO CLINIC-READY COMPOUNDS. BEYOND CORONAVIRUSES; FLAVIVIRUSES AND PICORNAVIRUSES ALSO CAUSE FREQUENT AND ONGOING EPIDEMICS WORLDWIDE AND HAVE NO EFFECTIVE THERAPEUTICS. MAINTAINING A PORTFOLIO OF NOVEL, CLINIC-READY THERAPEUTICS ARE CRITICAL FOR OUR FUTURE PANDEMIC PREPAREDNESS. THE AI-DRIVEN STRUCTURE-ENABLED ANTIVIRAL PLATFORM (ASAP) AVIDD CENTER WILL DEVELOP NOVEL CHEMICAL ASSETS THAT HAVE ANTIVIRAL ACTIVITY AGAINST THREE TARGET VIRAL FAMILIES. ASAP WILL LEVERAGE STATE-OF-THE-ART STRUCTURE-ENABLED TECHNOLOGIES CAPABLE OF LEVERAGING RECENT ADVANCES IN AI/ML AND COMPUTATIONAL CHEMISTRY IN IDENTIFYING, ENABLING, AND PROSECUTING DISCOVERY CAMPAIGNS AGAINST NOVEL VIRAL TARGETS. ASAP IS BUILT ON PRINCIPLES OF OPEN SCIENCE AND RAPID DISSEMINATION (ENABLED BY A DEDICATED DATA INFRASTRUCTURE CORE). ASAP BUILDS ON THE SUCCESSFUL COVID MOONSHOT, AN OPEN SCIENCE COLLABORATION THAT RECENTLY SECURED $11 MILLION FROM THE WELLCOME TRUST VIA THE WHO ACCESS TO COVID TOOLS ACCELERATOR (ACT-A) TO FUND PRECLINICAL DEVELOPMENT OF A NOVEL ORAL NONCOVALENT SARS-COV-2 ANTIVIRAL ACTING AGAINST THE MAIN PROTEASE (MPRO). BEGINNING WITH A HIGH-THROUGHPUT X-RAY FRAGMENT SCREEN, THE DISCOVERY TEAM SPENT JUST 18 MONTHS AND $1M TO REACH THE PRECLINICAL PHASE. ASAP WILL MIRROR THIS RAPID, COST-EFFICIENT APPROACH: AUTOMATED STRUCTURAL BIOLOGY AT DIAMOND LIGHT SOURCE (FRANK VON DELFT); AI/ML SYNTHESIS MODELS FROM POSTERA (ALPHA LEE); NANOSCALE CHEMISTRY AND COVALENT FRAGMENT LIBRARIES FROM NIR LONDON; MASSIVELY DISTRIBUTED FREE ENERGY CALCULATIONS ON FOLDING@HOME (JOHN CHODERA); AN INDUSTRIAL MEDICINAL CHEMISTRY TEAM LED BY MEDCHEMICA (ED GRIFFEN); AND ANTIVIRAL ASSAYS AND VIROLOGY EXPERTISE AT MOUNT SINAI (KRIS WHITE; ADOLFO GARCIA-SASTRE). ASAP AUGMENTS THIS SEASONED ANTIVIRAL DISCOVERY TEAM WITH NEW APPROACHES TO RESISTANCE-ROBUST TARGETING (KARLA KIRKEGAARD AND MATT BOGYO, STANFORD) AND DEEP MUTATIONAL SCANNING (JESSE BLOOM, FRED HUTCH). ASAP IS SUPPORTED BY THE DRUGS FOR NEGLECTED DISEASES INITIATIVE (DNDI) (PI BEN PERRY), AND LETTERS OF SUPPORT FROM TAKEDA, PFIZER, NOVARTIS, AND GRUPO INSUD. ASAP IMPACT: ASAP WILL BECOME THE NEXUS OF A ROBUST GLOBAL ANTIVIRAL DISCOVERY COMMUNITY. OUR OPEN SCIENCE APPROACH FOCUSES ON ENSURING GLOBAL, EQUITABLE ACCESS TO THERAPEUTICS TO COMBAT FUTURE PANDEMICS. WE AIM TO PRODUCE A ROBUST ANTIVIRAL PIPELINE CONSISTING OF 3 NEW PHASE I READY CANDIDATES, 6 LEAD OPTIMIZATION CAMPAIGNS, 9 FRAGMENT-TO-LEAD CAMPAIGNS, AND 10 STRUCTURE-ENABLED RESISTANCE-ROBUST VIRAL TARGETS. OUR ASSOCIATED DATA PACKAGES WILL ACCELERATE FOLLOW-ON DEVELOPMENT AND INVESTMENT."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"STANFORD UNIVERSITY","value":69058677,"savings":28731213,"link":null,"description":"DEVELOPMENT OF OUTPATIENT ANTIVIRAL COCKTAILS AGAINST SARS-COV-2 AND OTHER POTENTIAL PANDEMIC RNA VIRUSES. - ABSTRACT: THE OVERALL PLATFORM AND OBJECTIVE OF THE STANFORD AVIDD CENTER, “SYNERX,” IS TO DEVELOP OUTPATIENT ANTIVIRAL COCKTAILS AGAINST SARS-COV-2 AND OTHER POTENTIAL PANDEMIC RNA VIRUSES. THUS, THE GOAL OF EACH OF OUR 7 PROJECTS IS TO DEVELOP TOWARDS THE CLINIC A NOVEL DIRECT-ACTING ANTIVIRAL (DAA) WITH A DISTINCT MECHANISM OF ACTION, SO THAT THEY CAN BE USED ALONE AND IN COMBINATION WITH OTHER AGENTS—PROVIDING ADDITIVE, AND IDEALLY SYNERGISTIC ANTIVIRAL ACTIVITY. TO MAXIMIZE THE ACHIEVEMENT OF THIS GOAL, WE SEEK TO CREATE 3 SCIENTIFIC CORES THAT WILL EACH PROVIDE CRITICAL EXPERTISE AND RESOURCES: THE STRUCTURAL BIOLOGY CORE TO OFFER CRITICAL INSIGHTS INTO OUR PROJECTS’ ANTIVIRAL TARGETS AND MECHANISMS OF ACTION; THE PANDEMIC ASSISTANCE CORE TO ENSURE ADEQUATE ACCESS TO FACILITIES WITH THE REQUISITE BIOSAFETY AND CONTAINMENT TO SAFELY DEVELOP OUR PROJECTS’ ANTIVIRALS AGAINST SARS-COV-2 AND OTHER POTENTIAL RNA PANDEMIC VIRUSES; AND THE TRANSLATION ACCELERATOR CORE, IN WHICH IS EMBEDDED THE INDUSTRY CONSULTANTS CONSORTIUM, (ICC) TO PROVIDE THE REQUISITE TRANSLATIONAL RESOURCES, INDUSTRY RIGOR AND EXPERTISE TO ADVANCE EACH PROJECT IN A MILESTONE AND GO/NO-GO DRIVEN FASHION. THE RANGE OF PLANNED ACTIVITIES SPANS THE TRANSLATIONAL SPECTRUM, FROM INNOVATIVE TARGET DISCOVERY AND LEAD IDENTIFICATION, TO LEAD OPTIMIZATION AND IND-ENABLING ACTIVITIES. OUR ANTIVIRAL MODALITIES INCLUDE SMALL MOLECULES, NUCLEIC ACIDS, AND PROTEIN THERAPEUTICS. OUR LEAD PROGRAMS HAVE DEMONSTRATED PROOF- OF-CONCEPT IN VIVO ANTIVIRAL EFFICACY, WITH THE POTENTIAL TO COMBAT CORONAVIRUSES, AS WELL AS OTHER RNA VIRUSES OF PANDEMIC POTENTIAL. THESE EFFORTS WILL INCLUDE: A) TARGETING HIGHLY CONSERVED RNA STRUCTURES IN VIRAL RNA GENOMES WITH LOCKED NUCLEIC ACID (LNA) ANTISENSE OLIGONUCLEOTIDE (ASO) AND SMALL MOLECULE THERAPEUTICS; B) IMPROVING FORMULATIONS AND DELIVERY METHODS FOR NUCLEIC ACID THERAPEUTICS, AND TARGETING VIRUS-DERIVED CIRCULAR RNAS; C) SELECTIVELY TARGETING VIRAL ENVELOPES ANTIVIRAL PEPTIDES AND PEPTOIDS; D) DEVELOPING SMALL MOLECULE LIGANDS OF ESSENTIAL VIRAL PROTEINS THAT INDUCE SELECTIVE DEGRADATION OF THEIR PROTEIN TARGETS; E) DEVELOPING POTENT AND SELECTIVE INHIBITORS OF ESSENTIAL PROTEASES OF SARS-COV-2 AND OTHER RNA VIRUSES; F) DEVELOPING SMALL MOLECULE INHIBITORS OF SARS-COV-2 EXONUCLEASE TO BOTH PROMOTE LETHAL MUTAGENESIS OF THE VIRAL GENOME AS WELL AS ENHANCE THE ANTIVIRAL EFFICACY OF RIBONUCLEOSIDE ANALOGS; G) DEVELOPING SMALL MOLECULE INHIBITORS OF SARS-COV-2 NSP4’S ROLE IN MEMBRANE-ASSOCIATED RNA REPLICATION. WE WILL ESTABLISH AN ADMINISTRATIVE CORE TO EFFECTIVELY MANAGE AND OPTIMALLY SUPPORT THE ABOVE, AND PROVIDE CRITICAL REGULATORY EXPERTISE. FINALLY, WE WILL LEVERAGE AVIDD FUNDING WITH INSTITUTIONAL SUPPORT, MATCHING PHILANTHROPY AND INDUSTRY PARTNERSHIPS, AND STRATEGIC RELATIONSHIPS TO MAXIMIZE PRECLINICAL DEVELOPMENT AND ENSURE SUCCESSFUL CLINICAL AND COMMERCIAL DEVELOPMENT OF SYNERX’S MOST PROMISING LEAD MOLECULES. SUCCESSFUL ACCOMPLISHMENT OF OUR AIMS WILL YIELD EXCITING SYNERGISTIC OUTPATIENT ANTIVIRAL COCKTAILS FOR SARS-COV-2 AND OTHER RNA VIRUSES OF PANDEMIC POTENTIAL."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"SUNY, STONY BROOK","value":2933079,"savings":2478352,"link":null,"description":"STONY BROOK UNIVERSITY LABORATORY FOR COMPARATIVE MEDICINE TO SUPPORT PANDEMIC PREPAREDNESS - PROJECT SUMMARY/ABSTRACT THE LABORATORY FOR COMPARATIVE MEDICINE (LCM) AT STONY BROOK UNIVERSITY IS A RECENTLY CONSTRUCTED, STATE-OF- THE-ART ANIMAL BIOSAFETY LEVEL 3 (ABSL3) FACILITY. THE LCM IS ACTIVELY ENGAGED IN BASIC, TRANSLATIONAL, AND PRECLINICAL RESEARCH ON SARS-COV-2, THE VIRAL AGENT OF THE CURRENT COVID-19 WORLDWIDE PANDEMIC. RESEARCH IN THE LCM SERVES MULTIPLE INDIVIDUAL INVESTIGATORS AND GROUPS, BOTH WITHIN AND OUTSIDE OF STONY BROOK UNIVERSITY, AND INCLUDES COMMERCIAL AS WELL AS ACADEMIC INTERESTS. STONY BROOK HAS A LONG HISTORY OF EXCELLENCE IN MICROBIAL PATHOGENESIS RESEARCH, INCLUDING STUDIES ON PANDEMIC POTENTIAL VIRUSES OF CONCERN IN THE FAMILIES CORONAVIRIDAE (SARS-COV-2), BUNYAVIRALES (HANTAVIRUSES), FLAVIVIRIDAE (DENGUE, ZIKA, AND POWASSAN VIRUSES), AND PICORNAVIRIDAE (POLIOVIRUS). STONY BROOK VIROLOGISTS ARE ALSO CONDUCTING ONGOING STUDIES IN HUMAN IMMUNODEFICIENCY VIRUS AND INFLUENZA A VIRUS. OUR RESEARCH OVER THE PAST FIVE YEARS HAS COVERED THREE DIFFERENT RNA VIRUS FAMILIES RELEVANT UNDER THE AMERICAN PANDEMIC PREPAREDNESS/PANDEMIC PREPAREDNESS EFFORT, AND OUR CUMULATIVE EXPERIENCE COVERS FOUR OF THE VIRAL FAMILIES OF CONCERN. IN ADDITION TO VIRUSES OF CONCERN, ACTIVE RESEARCH AT STONY BROOK AND IN THE LCM INCLUDES WORK ON THE HIGHLY VIRULENT BACTERIAL AGENTS RICKETTSIA SPP. OF THE SPOTTED FEVER GROUP, FRANCISELLA TULARENSIS, A SELECT AGENT AND CAUSE OF THE ZOONOTIC DISEASE TULAREMIA, AND MYCOBACTERIUM TUBERCULOSIS, CAUSATIVE AGENT OF TUBERCULOSIS. TO IMPROVE FACILITY OPERATIONS AND ENHANCE ONGOING AND FUTURE RESEARCH IN THE LCM, WE ARE REQUESTING FOUR UPGRADES TO THE LCM: 1) REPLACEMENT OF THE HIGH TEMPERATURE HOT WATER UNFIRED STEAM BOILERS AND CONVERSION OF THE HIGH TEMPERATURE AND HOT WATER SYSTEMS; 2) PURCHASE AND INSTALLATION OF A WASHER FOR ANIMAL CAGES AND RACKS; 3) PURCHASE AND INSTALLATION OF A FLUORESCENCE-ACTIVATED CELL SORTER AND CUSTOM BIOSAFETY ENCLOSURE; AND 4) ACQUISITION OF A REAL-TIME, QUANTITATIVE REVERSE-TRANSCRIPTION PCR MACHINE. THE REQUESTED UPGRADES WILL SUPPORT AND IMPROVE PANDEMIC PREPAREDNESS-RELEVANT RESEARCH IN THE LCM, ADVANCE STUDIES ON HIGHLY VIRULENT AND EMERGING PATHOGENS, AND PROVIDE ENHANCED RESOURCES NOT ONLY TO STONY BROOK RESEARCHERS, BUT ALSO TO STATE AND REGIONAL EFFORTS TO COMBAT CURRENT AND FUTURE PANDEMIC THREATS. THE REQUESTED IMPROVEMENTS WILL SUPPORT THE DEVELOPMENT OF ANTIVIRAL PROGRAMS AND ANTIMICROBIAL PREVENTIVE AND THERAPEUTIC MEASURES."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"TULANE UNIVERSITY, DELTA REGIONAL PRIMATE CENTER","value":2396052,"savings":865506,"link":null,"description":"Project Summary – Overall The Tulane National Primate Research Center (TNPRC) is affiliated with Tulane University of Louisiana and was dedicated in 1964. The Center is part of Tulane University Health Sciences along with the School of Medicine, the School of Public Health and Tropical Medicine, and the School of Science and Engineering. The TNPRC is one of seven NIH-supported National Primate Research Centers within the National Primate Research Center Program. This application requests funding for the five-year time-period of May 1, 2023-April 30, 2028. Funds will be used to support administration, operations, animal resources, scientific research resources, a pilot research program, alteration and renovations, outreach, and education and training activities of the Center. The animal resources program is fully accredited by AAALAC with exemplary status. Significant infrastructure projects have been completed including renovation of new laboratory space and completion of the PET/CT facility within the RBL. We have completed a large infrastructure upgrade with upgraded boilers and new and increased capacity chillers, new building automation and access controls and energy efficiency lighting upgrades, as well as upgrades in stormwater and wastewater treatment improvements. The period since the last renewal of the TNPRC base grant has been a time of sustained growth and programmatic change. Total funding for the Center has increased to more than $43.8M in FY2021. The TNPRC is the only NPRC to have a Regional Biosafety Laboratory (BSL-3), which has been a key factor in obtaining funds to support numerous studies utilizing select agents, tuberculosis, and emerging infectious diseases, including a new and expanding program in SARS-CoV-2 research. Our efforts in SARS-CoV-2 have provided leadership within the NPRC system with the development of nonhuman primate models, testing therapeutics and vaccines. In addition, we developed a CoVID-19 Coordinating Center and Data Center supported by NIH, which provides coordinated and collaborative interactions with other NPRCs. The development of our strong Quality Assurance and Quality Control Program and new High Containment Research Performance Core have contributed greatly to our success during this funding period. In the next grant period, we will recruit additional faculty and expand our research efforts into chronic and comorbid conditions associated with infections and aging. We will focus on building onto our current successes with the generation of a new strategic plan that will make TNPRC the best primate center we can be and a premiere place to work for our employees."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF CALIFORNIA","value":3069950,"savings":2128626,"link":null,"description":"CALIFORNIA NATIONAL PRIMATE RESEARCH CENTER"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF CALIFORNIA","value":5654777,"savings":774779,"link":null,"description":"CALIFORNIA NATIONAL PRIMATE RESEARCH CENTER"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF CALIFORNIA, IRVINE","value":727670,"savings":532964,"link":null,"description":"SUMMARY Humanity is confronting a pandemic caused by the new Corona Virus 2 (SARS-CoV-2) infection. Our long- term goal is to develop a potent prophylactic pan-Coronavirus vaccine to stop/reduce past, current and future Coronavirus infections and/or diseases. While SARS-CoV-2-induced antibody and CD4+ and CD8+ T cell responses are critical to reducing viral infection in the majority of asymptomatic individuals, an excessive proinflammatory cytokine storm appears to lead to acute respiratory distress syndrome in many symptomatic individuals. Major gaps: Identifying the epitope specificities, the phenotype and function of B cells, CD4+ T cells and CD8+ T cells associated with “natural protection seen in asymptomatic individuals (those who are infected, but never develop any major symptoms) should guide the development of a future coronavirus vaccine. Preliminary Results: We have made significant progress in: (A) Identifying a priori potential human B-cell, CD4+ and CD8+ T cell target epitopes from the whole SARS-CoV-2 genome; (B) Identifying “universal” epitopes conserved and common between: (1) previous SARS and MERS coronavirus outbreaks, (2) current 4388 SARS-CoV-2 strains that now circulate in the United States and 184 other countries; and (3) SARS-like coronavirus strains currently found in bats that have the potential to produce future human outbreaks; (C) Applying our scalable self-assembling protein nanoparticles (SAPNs) antigen delivery platform to produce prototype multi-epitope pan-Coronavirus vaccine candidates, that incorporate conserved protective epitopes from human and bats Coronaviruses, and demonstrated their B- and T-cell immunogenicity in HLA transgenic mice; and (D) Generating a novel “humanized” susceptible HLA-DR/HLA-A*0201/hACE2 triple transgenic mouse model in which to test these vaccine candidates. Our hypothesis is that one of our pan-Coronavirus vaccine candidates, containing conserved “asymptomatic” SARS-CoV-2 B- and T-cell epitopes that are mainly recognized by the immune system of “protected,” asymptomatic individuals would protect from SARS-CoV-2 infection and disease, upon intranasal delivery. To test this hypothesis our Specific Aims are: Aim 1: To test in vitro the antigenicity of conserved Coronavirus epitopes, we recently identified from the whole SARS-CoV-2 genome, using blood-derived antibodies, CD4+ T-cells and CD8+ T-cells from SARS-CoV-2-infected symptomatic vs. asymptomatic individuals. The immunodominant conserved “asymptomatic” epitopes will be identified and used in our multi-epitope pan-Coronavirus vaccine candidates. Aim 2: To test in vivo the safety, immunogenicity, and protective efficacy of highly conserved multi-epitope pan-Coronavirus vaccine candidates, delivered mucosally, to our novel “humanized” susceptible triple transgenic mouse model. Successful completion of this preclinical vaccine project is expected to identify a broadly protective pan- Coronavirus vaccine candidate that could quickly proceed into an FDA Phase 1 clinical trial."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS","value":197887440,"savings":45257547,"link":null,"description":"Abstract This supplement will support ACTIV-2D ACTIV-2D is a master protocol to evaluate the safety and efficacy of investigational agents for the treatment of symptomatic non-hospitalized adults with SARS-CoV-2 infection. The protocol is a phase III multicenter, randomized, double blind trial to evaluate the safety and efficacy of S-217622 for the treatment of symptomatic high-risk non-hospitalized adults with SARS-CoV-2 infection. The primary outcome is to determine if the investigational agent (S-217622) will prevent the composite endpoint of hospitalization due to any cause or death due to any cause through study Day 29. Hospitalization is defined as ≥24 hours of acute care, in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe coronavirus disease 2019 (COVID-19) during the COVID-19 pandemic."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS","value":170881829.83,"savings":43904251,"link":null,"description":"Abstract This supplement will support ACTIV-2D ACTIV-2D is a master protocol to evaluate the safety and efficacy of investigational agents for the treatment of symptomatic non-hospitalized adults with SARS-CoV-2 infection. The protocol is a phase III multicenter, randomized, double blind trial to evaluate the safety and efficacy of S-217622 for the treatment of symptomatic high-risk non-hospitalized adults with SARS-CoV-2 infection. The primary outcome is to determine if the investigational agent (S-217622) will prevent the composite endpoint of hospitalization due to any cause or death due to any cause through study Day 29. Hospitalization is defined as ≥24 hours of acute care, in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe coronavirus disease 2019 (COVID-19) during the COVID-19 pandemic."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS","value":20566378,"savings":11037173,"link":null,"description":"Abstract This supplement will support ACTIV-2D ACTIV-2D is a master protocol to evaluate the safety and efficacy of investigational agents for the treatment of symptomatic non-hospitalized adults with SARS-CoV-2 infection. The protocol is a phase III multicenter, randomized, double blind trial to evaluate the safety and efficacy of S-217622 for the treatment of symptomatic high-risk non-hospitalized adults with SARS-CoV-2 infection. The primary outcome is to determine if the investigational agent (S-217622) will prevent the composite endpoint of hospitalization due to any cause or death due to any cause through study Day 29. Hospitalization is defined as ≥24 hours of acute care, in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe coronavirus disease 2019 (COVID-19) during the COVID-19 pandemic."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF CALIFORNIA-SAN FRANCISCO","value":67452049,"savings":12347604,"link":null,"description":"QCRG PANDEMIC RESPONSE PROGRAM - QCRG PANDEMIC RESPONSE PROGRAM OVERALL SUMMARY THE QCRG (QUANTITATIVE BIOSCIENCES INSTITUTE CORONAVIRUS RESEARCH GROUP) PANDEMIC RESPONSE PROGRAM IS AN INTERDISCIPLINARY PROGRAM THAT AIMS TO IDENTIFY NEW DIRECT-ACTING ANTIVIRALS FOR SARS-COV-2 AND 19 OTHER VIRUSES. THE PROPOSAL BRINGS TOGETHER A TEAM OF 45 INVESTIGATORS FROM 14 DIFFERENT INSTITUTIONS WITH A HISTORY OF COLLABORATION; 31 OF THESE HAVE CO-PUBLISHED TOGETHER ON 25 PAPERS ON SARS-COV-2,1–25 EFFORTS THAT HAVE LAID A STRONG FOUNDATION FOR THE QCRG PANDEMIC RESPONSE PROGRAM. INITIALLY, WE WILL FOCUS ON EIGHT TARGET CLASSES FROM EIGHT VIRAL FAMILIES (CORONAVIRIDAE, PICORNAVIRIDAE, TOGAVIRIDAE, FLAVIVIRIDAE, HANTAVIRIDAE, ARENAVIRIDAE, NAIROVIRIDAE AND PARAMYXOVIRIDAE), INCLUDING SEVEN CORONAVIRUSES, WITH A FOCUS ON SARS-COV-2, WHERE THE VIRAL RNA AND 12 PROTEINS WILL BE TARGETED. IN ADDITION TO THE SARS-COV-2 RNA (PROJECT 1), WE WILL TARGET THE NSP3 PLP AND NSP5 MPRO PROTEASES (PROJECT 2); THE NSP3 MACRODOMAIN (PROJECT 5); THE RDRP POLYMERASE, NSP7, NSP8 AND NSP12 (PROJECT 2) THE STRUCTURAL PROTEINS E (PROJECT 3), N (PROJECT 6) AND M (PROJECTS 3 AND 6); THE METHYLTRANSFERASES NSP10/16 AND NSP14 (PROJECT 4); AND THE ACCESSORY PROTEIN INVOLVED IN REGULATING THE IMMUNE RESPONSE, ORF9B (PROJECT 6). ALTHOUGH WE WILL FOCUS ON SARS-COV-2, RELATED PROTEINS FROM 19 OTHER VIRUSES WILL ALSO BE TARGETED. USING THE QCRG DRUG DISCOVERY PLATFORM, WE WILL PERFORM SCREENS ON THESE TARGETS, INVOLVING FRAGMENT CAMPAIGNS, VIRTUAL LIBRARY DOCKING, AND HIGH-THROUGHPUT SCREENS, TO DISCOVER INHIBITORS, WHICH WILL BE OPTIMIZED USING CYCLES OF DESIGN, STRUCTURE DETERMINATION, AND TESTING. IN VITRO AND IN VIVO PHARMACOKINETICS AS WELL AS ACTIVITY IN CELLULAR AND MOUSE MODELS OF INFECTION WILL BE CARRIED OUT, FOLLOWED BY STUDIES INVOLVING ORAL BIOAVAILABILITY, CLEARANCE, PERMEABILITY, SOLUBILITY, METABOLIC LIABILITIES, TOXICITY AND EFFICACY. THE FINAL GOAL OF EACH PROJECT IS AN OPTIMIZED LEAD READY FOR CLINICAL DEVELOPMENT AT ROCHE (SEE LETTER OF SUPPORT FROM DR. JOHN YOUNG, HEAD OF INFECTIOUS DISEASES) AND OTHER INDUSTRY PARTNERS. THROUGHOUT, WE WILL EXPLOIT AN INTEGRATED SUITE OF EXPERIMENTAL AND COMPUTATIONAL TECHNOLOGIES PROVIDED BY EIGHT CORES. THE BIOCHEMISTRY CORE WILL PROVIDE PURIFIED MATERIAL FOR THE SCREENING CORE, WHILE THE STRUCTURES OF TARGETS AND COMPOUNDS WILL BE DETERMINED THROUGH THE CRYO-EM, CRYO-ET AND CRYSTALLOGRAPHY CAPABILITIES OF THE STRUCTURAL BIOLOGY CORE. STATE-OF-THE-ART MASS SPECTROMETRY IN THE PROTEOMICS CORE WILL PROVIDE MECHANISTIC INSIGHT INTO THE EFFECTS OF COMPOUNDS ON THEIR TARGETS. THE MEDICINAL CHEMISTRY CORE WILL OPTIMIZE POTENT ON- TARGET COMPOUNDS AND WORK CLOSELY WITH THE IN VITRO VIROLOGY CORE AND IN VIVO VIROLOGY CORE TO MEASURE AND OPTIMIZE ANTIVIRAL ACTIVITY. THE INTEGRATIVE MODELING CORE WILL PROVIDE COMPUTATIONAL SUPPORT TO STRUCTURE DETERMINATION AND INHIBITOR DISCOVERY THROUGHOUT THE QCRG DRUG DISCOVERY PLATFORM. THE ADMINISTRATIVE CORE WILL PROVIDE LEADERSHIP, HELP TO FOSTER A COLLABORATIVE ENVIRONMENT, AND MANAGE THE MENTORED PROJECTS AND THE DEVELOPMENTAL RESEARCH PROJECTS, WHICH WILL BRING IN NEW INVESTIGATORS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF MARYLAND","value":414425,"savings":127165,"link":null,"description":"PROJECT SUMMARY In this emergency R21 effort we propose to implement a set of novel studies designed to improve our fundamental understanding of SARS-CoV-2 aerobiology. Through a combination of theoretical, experimental, and epidemiological data, there is emerging consensus that respiratory aerosols play a primary role in the transmission of COVID-19. However, despite the importance of understanding the fundamental mechanisms involved in the airborne transmission route, a number of basic questions central to SARS-CoV-2 aerobiology remain unanswered. In particular, the distribution of SARS-CoV-2 particles within different aerosol size populations has not yet been studied in detail, nor is there data available to predict the viability and infectivity of individual airborne virus particles within different aerosol populations. Furthermore, it is not currently known whether the virus tends to be uniformly distributed within a given aerosol population or clustered within a small number of aerosol droplets, an essential question for understanding the quantum of infection for COVID-19 transmission. To address these challenges, we propose a novel analytical approach combining efficient sampling of exhaled breath, high resolution fractionation of aerosol ensembles, and coupled analysis of inactive and infective virus particles within the collected aerosol fractions through a combination of RT-PCR and viral plaque assays. Significantly, aerosol fractionation will be performed using an Aerodynamic Aerosol Classifier as a unique technology for isolating monodisperse aerosol populations. In addition, a new technique for discretizing the collected aerosol particles will be implemented using a thermo-responsive hydrogel for aerosol deposition, allowing the particles to be delivered to cell culture while remaining spatially isolated and elucidating virus distribution and clustering within a given size fraction. The combined data sets resulting from the proposed studies will provide a first view of the distribution and conformation of SARS-CoV-2 within respiratory aerosols, and the relationships between aerosol properties (size, virus content, virus distribution, and clustering) and downstream infectivity. We anticipate that the improved understanding of aerosolized virus infectivity emerging from these studies will illuminate fundamental aspects of COVID-19 airborne transmission and allow us to identify the quantum of infection associated with SARS-CoV-2, thus supporting accurate modeling of transmission dynamics and guiding improved recommendations for PPE, room ventilation, and sanitation protocols to enhance intervention and minimize transmission of the virus."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS","value":26702445,"savings":3489855,"link":null,"description":"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS","value":3365966,"savings":165595,"link":null,"description":"Project Summary/Abstract The University of Maryland School of Medicine (UMSOM) Center for Vaccine Development and Global Health (CVD) has been an established VTEU site since 1974. The goal of the VTEUs is to initiate innovative concepts for clinical research and implement clinical site protocols for evaluating vaccines, other preventive biologics, therapeutics, diagnostics, and devices for the treatment and prevention of infectious diseases, and CVD is uniquely poised to accomplish this goal. CVD's expert and accomplished investigative team has complementary skill sets in all areas necessary to address the NIAID priority areas, with established management plans to effectively allocate work and conduct multiple projects simultaneously. CVD is internationally recognized for our capacity and capability to conduct controlled human infection trials for malaria, influenza, and enteric pathogens and to implement treatment and prevention trials in endemic areas for malaria and neglected tropical diseases (NTD), both of which have been a focus of its research for many years. CVD has access to U.S. populations of healthy subjects in all age groups for this research and subjects with special risks, such as patients attending outpatient clinics with sexually transmitted infection (STI) and other conditions that generally do not requiring hospitalization. Strong domestic collaborations at sites experienced in clinical trials provide the CVD's VTEU with surge capacity among healthy subjects of all ages and vulnerable populations such as pregnant women in the U.S. to address public health emergencies. CVD's international collaborators, including two long-standing permanent field sites in Africa, are an invaluable resource for vetted international trial sites in low resource countries endemic for malaria and NTD with experience in conducting high quality NIAID and VTEU studies. This proposal describes mechanisms to implement protocols that arise from concepts proposed by the Leadership Group (LG) and the research community including investigators from other VTEUs, academia, industry, non-governmental organizations, and DMID. These concepts will focus on NIAID priority areas, including malaria, NTD, respiratory infections, particularly influenza, enteric diseases, STI, and emerging infectious diseases and other infectious disease considerations. Under our VTEU contract that is nearing completion (2013-2023), CVD was awarded over 23 Task Orders, enrolled over 1,500 participants, and successfully collaborated with national and international sites. This renewal application is intended to supplement the new VTEU award (1UM1AI148689) that we received in December, 2019 in response to AI18-046; funding for this award was limited to one year as a result of an omission by our Sponsored Programs Administration to include a request for 7 full years of funding. The current proposal seeks to supplement that one year award with an additional 6 years of funding."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF MINNESOTA","value":66431207,"savings":15818441,"link":null,"description":"MIDWEST AVIDD CENTER - PROJECT 5 – PANDEMIC VIRUS HELICASE INHIBITORS ABSTRACT THE GOAL OF THIS PROJECT IS TO DEVELOP PAN-FAMILY, ANTIVIRAL DRUG CANDIDATES TARGETING THE VIRAL HELICASE OF CORONAVIRUS AND FLAVIVIRUS. ALL PRIORITY RNA VIRUSES ENCODE A VIRAL HELICASE DOMAIN IN THEIR GENOMES, AND THEY SHARE HIGH SIMILARITY IN STRUCTURE AND BIOCHEMICAL FEATURES. VIRAL RNA HELICASE IS A CRITICAL COMPONENT OF THE VIRAL REPLICASE COMPLEX AND IS ESSENTIAL FOR RNA VIRUS REPLICATION. FURTHER, IT SHOWS A HIGH SEQUENCE HOMOLOGY WITHIN THE VIRUS FAMILY (E.G., 100% IDENTITY WITHIN SARS2). CONSEQUENTLY, VIRAL RNA HELICASES CAN SERVE AS A NOVEL ANTIVIRAL TARGET FOR RNA VIRUSES WITH A HIGH BARRIER TO DRUG RESISTANCE. DURING THE PAST 10 YEARS, THE CHUNG LAB HAS MADE SIGNIFICANT CONTRIBUTIONS TO THE DEVELOPMENT OF ANTIVIRALS TARGETING THE ALPHAVIRUS HELICASE DOMAIN (NSP2) AND VALIDATED VIRAL HELICASE AS DRUGGABLE FOR DEVELOPING POTENT ANTIVIRALS. BASED ON THIS SUCCESS, WE HYPOTHESIZE THE VIRAL HELICASE CAN SERVE AS A VALID TARGET FOR SAFE AND EFFECTIVE ANTIVIRALS FOR SARS2 AND OTHER PRIORITY RNA VIRUSES. HERE, WE PROPOSE A COMPREHENSIVE ANTIVIRAL DISCOVERY CAMPAIGN TARGETING VIRAL HELICASE WITH A MULTI-DISCIPLINARY APPROACH COMBINING ULTRA-HIGH-THROUGHPUT SCREENING AND DNA-ENCODED CHEMISTRY TECHNOLOGY FOLLOWED BY A ROBUST HIT VALIDATION SCHEME WITH ANTIVIRAL TESTING, STRUCTURAL BIOLOGY, AND BIOCHEMICAL APPROACHES (AIM 1). FURTHER, WE PROPOSE TO ADVANCE PROMISING VIRAL HELICASE INHIBITOR HITS THROUGH HIT-TO-LEAD DEVELOPMENT, GIVING VALIDATED LEADS AS DRUG DEVELOPMENT CANDIDATES WITH MEDICINAL CHEMISTRY PAIRED WITH AI-BASED DRUG DESIGN, DMPK STUDIES, AND IN VIVO ANTIVIRAL EFFICACY STUDIES (AIM 2). FINALLY, WE WILL DELIVER 1-2 ORALLY BIOAVAILABLE, PATENTABLE, DRUGLIKE IND-ENABLED SMALL MOLECULES (A DEVELOPMENT CANDIDATE + BACKUP) THAT ARE WELL-SUITED FOR TRANSLATION BY A PHARMA PARTNER (AIM 3). OUR PROPOSAL IS SUPPORTED BY OUR DISCOVERY OF A NOVEL HIT COMPOUND (UNC0379) WITH AN ANTI-SARS2 ACTIVITY FROM A PILOT 100,000-COMPOUND LIBRARY SCREEN (CORE B). THE PI AND ESTABLISHED TEAM (CHUNG, VIROLOGY/PI; BANNISTER, MED. CHEM/DEPUTY; SPICER, UHTS; LUO, STRUCTURAL BIOLOGY OF VIRAL REPLICASE; RANEY, HELICASE BIOCHEMISTRY) SYNERGISTICALLY COMBINE ANTIVIRAL DRUG DISCOVERY (HEAD-GORDON, COMPCHEM/AI) WITH EXCELLENT CORE SUPPORT (CORE B AND CORE C). OUR EFFORT WILL DELIVER NEW CLASSES OF DIRECT HELICASE-TARGETING ANTIVIRAL AGENTS FOR SARS2 INFECTION AND OTHER HIGH PRIORITY VIRAL PATHOGENS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF NEBRASKA MEDICAL CENTER","value":3906967,"savings":1567022,"link":null,"description":"A BEDSIDE-TO-BENCH APPROACH TO PANDEMIC PREPAREDNESS - THE CLINICAL CAPABILITIES OF THE UNIVERSITY OF NEBRASKA MEDICAL CENTER (UNMC) AND ITS CLINICAL PARTNER, NEBRASKA MEDICINE (NM), PLAYED VITAL ROLES IN THE TREATMENT OF U.S. CITIZENS INFECTED WITH EBOLA IN 2014 AND THE EARLY RESPONSE TO THE COVID-19 PANDEMIC. WHILE THE PRESENCE OF THE NATIONAL QUARANTINE UNIT (NQU) AND THE NEBRASKA BIOCONTAINMENT UNIT (NBU) ON CAMPUS PROVIDED UNMC RESEARCHERS WITH SOME OF THE EARLIEST ACCESS TO INDIVIDUALS EXPOSED TO INFECTIOUS AGENTS (IN THE NQU), AS WELL AS THOSE WHO BEGIN TO DEVELOP DISEASE (IN THE NBU), WE RECOGNIZED A KEY GAP IN OUR CAPABILITIES IS THE LACK OF MODERN TECHNOLOGIES WITHIN OUR HIGH- CONTAINMENT SPACES REQUIRED TO GAIN GREATER INSIGHTS INTO THE PATHOGENIC MECHANISMS UTILIZED BY NEW AND EMERGING PATHOGENS. THEREFORE, THE OVERALL GOAL OF THIS PROPOSED PROJECT IS TO MODERNIZE OUR HIGH-CONTAINMENT RESEARCH LABORATORIES TO MAXIMIZE THEIR RESEARCH POTENTIAL AND TO LEVERAGE OUR CLINICAL EXPERTISE TO FOSTER RESEARCH ON VACCINE AND THERAPEUTIC DEVELOPMENT. THIS WILL BE ACHIEVED IN TWO WAYS: FIRST, WE WILL IMPROVE OUR BIOCONTAINMENT INFRASTRUCTURE WITHIN KEY BIOCONTAINMENT RESEARCH FACILITIES IN A WAY THAT INCREASES OUR CAPACITY TO CONDUCT RESEARCH ON HIGH-CONSEQUENCE PATHOGENS, MAXIMIZES SYNERGY BETWEEN THE VARIOUS BIOCONTAINMENT LABORATORIES, AND INCREASES BIOSECURITY. SECOND, WE WILL INVEST IN THE MODERN TECHNOLOGIES NEEDED IN OUR BSL-3 AND ABSL-3 LABORATORIES TO CONDUCT CUTTING-EDGE STUDIES ON NEW AND EMERGING PATHOGENS AND TO ADDRESS CRITICAL QUESTIONS RELATED TO DISEASE PATHOGENESIS. UPON COMPLETION, THESE IMPROVEMENTS WILL FOSTER MUCH GREATER SYNERGY BETWEEN THE CLINICAL AND RESEARCH ARMS OF UNMC AND NM, LEVERAGING EARLY ACCESS TO CLINICAL DATA/SAMPLES TO STREAMLINE RESEARCH INTO DISEASE PATHOGENESIS, AND TO ACCELERATE THE DEVELOPMENT OF NEW VACCINES AND THERAPEUTICS DURING FUTURE PANDEMICS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL","value":65483194,"savings":18518974,"link":null,"description":"RAPIDLY EMERGING ANTIVIRAL DRUG DEVELOPMENT INITIATIVE- AVIDD CENTER (READDI-AC) - PROGRAM SUMMARY/ABSTRACT EMERGING VIRUSES ARISE SUDDENLY AND CAUSE CONSIDERABLE MORBIDITY AND MORTALITY WORLDWIDE. TO PREPARE FOR CURRENT AND FUTURE THREATS, PUBLIC-PRIVATE PARTNERSHIPS ARE NEEDED TO CHANGE THE CURRENT REACTIVE RESPONSE PLATFORM INTO ONE THAT IS PROACTIVE. IN RESPONSE TO RFA-AI-21-050, THE RAPIDLY EMERGING ANTIVIRAL DRUG DEVELOPMENT INITIATIVES AVIDD CENTER (READDI-AC) IS AN INTEGRATED PUBLIC-PRIVATE PARTNERSHIP WITH A RENOWNED, INTERDISCIPLINARY RESEARCH TEAM OF EXPERTS, WHO APPLY CUTTING EDGE INNOVATIVE TECHNOLOGIES IN VIROLOGY, BIOCHEMISTRY, STRUCTURAL BIOLOGY, MEDICINAL CHEMISTRY, COMPUTATIONAL BIOLOGY, STRUCTURE-GUIDED DRUG DESIGN AND GENOMICS TO DEVELOP ORAL, POTENT, BROAD-SPECTRUM FAMILY-SPECIFIC ANTIVIRALS FOR CORONAVIRUSES, FLAVIVIRUSES, ALPHAVIRUSES AND FILOVIRUSES. TO ACHIEVE THESE GOALS, THE READDI-AC PROGRAM INCLUDES ACADEMIC LEADERS IN BASIC AND APPLIED ANTIVIRAL RESEARCH AND CHEMISTRY AS WELL AS INDUSTRY LEADERS JANSSEN PHARMACEUTICALS N.V.(JPNV), TAKEDA, CHIMERIX INC. AND PARDES BIOSCIENCES. OUR COMMERCIAL PARTNERS PROVIDE AN ENVIABLE TRACK RECORDS IN DRUG DISCOVERY AND PRODUCT DEVELOPMENT, AND LEADERSHIP IN MEDICINAL CHEMISTRY, PHARMACOLOGY, DRUG FORMULATION, TOXICITY STUDIES AND PHARMACOKINETICS, ESPECIALLY CRITICAL FOR DRIVING OPTIMIZED LEADS THROUGH PREIND ENABLING STUDIES TOWARD THE CLINIC. IMPORTANTLY, OUR INDUSTRY PARTNERS ALSO PROVIDE IN KIND MATCHING CONTRIBUTIONS, ACCESS TO HIGH QUALITY COMMERCIAL CHEMICAL LIBRARIES, EARLY HITS, OPTIMIZED LEADS, AND STATE OF THE ART HIGH- THROUGHPUT SCREENS. THE IMMEDIATE AND LONG-TERM GOALS OF READDI-AC ARE TO: A) VALIDATE DRUGGABLE TARGETS IN CONSERVED VIRAL PROTEINS, B) IDENTIFY HITS AND LEADS USING SAR AND STATE OF THE ART BIOCHEMICAL AND ENZYMATIC ASSAYS, C) OPTIMIZE/FORMULATE CHEMICAL PROBES AND LEAD COMPOUNDS AS BROADLY ACTING ORAL COMPOUNDS WITH ACTIVITY AGAINST MULTIPLE RELEVANT MEMBERS OF EACH EMERGING VIRUS FAMILY; D) PROVIDE CRITICAL LATE-STAGE PRECLINICAL DEVELOPMENT AND IND-ENABLING IN VIVO STUDIES FOR TWO BROADLY ACTIVE, ORAL DRUG CANDIDATES; E) PROMOTE OPEN SCIENCE SHARING OF UNUSED CHEMICAL ASSETS, CHEMICAL PROBES, METHODS, REAGENTS AND ASSAYS FOR INNOVATIONS BY CROWDSOURCING; F) BUILD CAPACITY AND TRAINING IN 21ST CENTURY VIRAL DRUG DISCOVERY AND DEVELOPMENT BY COUPLING INNOVATIVE APPROACHES IN TARGET DISCOVERY AND VALIDATION WITH STATE OF THE ART TECHNIQUES, INTEGRATED WORKFLOWS AND NOVEL DISCOVERY PLATFORMS FOR HIT TO LEAD PROGRESSION AND SAR OPTIMIZATION. READDI-AC HAS FIVE RESEARCH PROJECTS AND FOUR HIGHLY INTERACTIVE CORES THAT ESTABLISH A COOPERATIVE LANDSCAPE THAT BUILDS LEADERSHIP, EXPERTISE, RESPONSE CAPACITY AND PARTNERSHIPS THAT INVIGORATE 21ST CENTURY DRUG DEVELOPMENT."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL","value":3812960,"savings":317121,"link":null,"description":"GENETIC ANALYSIS OF COVID-19 SUSCEPTIBILITY AND RESISTANCE DETERMINANTS IN THE COLLABORATIVE CROSS"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF PITTSBURGH, THE","value":7480973,"savings":6748961,"link":null,"description":"ENHANCING THE SAFETY, EFFICIENCY, AND RESEARCH CAPACITY OF THE UNIVERSITY OF PITTSBURGH REGIONAL BIOCONTAINMENT LABORATORY TO STUDY VIRUS FAMILIES OF GREATEST PANDEMIC CONCERN - ABSTRACT. IN 2008, THE UNIVERSITY OF PITTSBURGH OPENED A REGIONAL BIOCONTAINMENT LABORATORY (RBL). RESEARCH AT THE RBL HAS GROWN SIGNIFICANTLY SINCE THEN, WITH INVESTIGATORS WORKING ON SEVERAL HIGHLY INFECTIOUS MICROBIAL AGENTS REQUIRING BSL2 AND ABSL2 FACILITIES. CURRENT RBL RESEARCH PROJECTS COVER MULTIPLE VIRUSES IN 5 OF THE 7 RNA VIRUS FAMILIES OF PANDEMIC CONCERN AS DEFINED BY NIH, INCLUDING, BUNYAVIRALES, CORONAVIRIDAE, FLAVIVIRIDAE, PARAMYXOVIRIDAE, AND TOGAVIRIDAE. THE RBL IS AN INVALUABLE RESOURCE FOR THE UNIVERSITY OF PITTSBURGH, WESTERN PENNSYLVANIA, AND INSTITUTIONS IN THE US, EUROPE AND SOUTH AMERICA. INDEED, THE RBL RECEIVED THE SARS-COV-2 VIRUS IN MID-FEBRUARY, 2020, AND RECEIVED ALMOST $5M IN MARCH 2020 FROM THE INTERNATIONAL COALITION FOR EPIDEMIC PREPAREDNESS INNOVATIONS TO PURSUE VACCINE DEVELOPMENT FOR COVID-19. THE CONTINUED SUCCESS OF THE RBL IS ESSENTIAL FOR THE US TO CONDUCT THE NECESSARY RESEARCH TO BE PREPARED FOR THE RAPID DEVELOPMENT AND TESTING OF VACCINES AND THERAPEUTICS IN RESPONSE TO FUTURE PANDEMICS SIMILAR TO THE RECENT SARS-COV-2. OVER THE LAST 14 YEARS, THE INFRASTRUCTURE AND FACILITIES IN THE RBL HAVE BEGUN TO DEGRADE, WITH SOME REACHING THE END OF THEIR USEFULNESS. THE FOCUS OF THIS APPLICATION IS TO MODERNIZE THE RBL THROUGH BOTH UPGRADES AND RENOVATIONS THAT ARE DESIGNED TO ALLOW FOR CONTINUING CUTTING-EDGE RESEARCH ON INFECTIOUS AGENTS OF PANDEMIC CONCERN FOR MANY YEARS TO COME. AN EFFECTIVE AND EFFICIENT RBL IS A VITAL TOOL FOR PANDEMIC PREPAREDNESS. TO ACCOMPLISH OUR GOALS, 3 AREAS OF RBL FUNCTIONALITY AND EFFICIENCY WILL BE ADDRESSED. FIRST, WE WILL ENHANCE RBL SAFETY AND LONGEVITY. REPAIRS OR REPLACEMENTS WILL BE MADE TO THE BIO- CONTAINMENT FLOORING, THE SUPPLY AIR SYSTEM, THE EXHAUST SYSTEM, VARIABLE FREQUENCY DRIVES, CHILLER CONTROLS, STEAM WATER HEATERS, DIESEL ENGINE GENERATOR FUEL SYSTEM CONTROLS, FIRE ALARM SYSTEM, BUILDING AUTOMATION SYSTEM, WALK-IN COOLER, AND BIOMETRIC SECURITY. SECOND, THE EFFICIENCY OF RBL OPERATIONS WILL BE ENHANCED BY REPLACEMENT OF EXISTING SYSTEM LIGHTING WITH ENERGY-EFFICIENT LED LIGHTS AND REMOVAL OF A GAS PLASMA STERILIZER TO GENERATE MUCH NEEDED SPACE. THIRD, THE RESEARCH CAPACITY OF THE RBL WILL BE ENHANCED BY INCREASING RODENT HOUSING CAPACITY AND PURCHASING ADDITIONAL CAGING FOR NON-HUMAN PRIMATES, RABBITS, AND FERRETS. THE ULTIMATE GOAL OF THIS PROPOSAL IS TO ENSURE THE RBL REMAINS FUNCTIONAL, EFFICIENT, AND READY FOR RAPID RESPONSE TO FUTURE EMERGING PANDEMICS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF ROCHESTER","value":10005677,"savings":1598936,"link":null,"description":"The Vaccine and Treatment Evaluation Units (VTEUs) are a critical resource for the NIAID Infectious Diseases Clinical Research Consortium to conduct clinical research and trials to evaluate vaccines, preventive biologics, therapeutics, diagnostics, predictive markers, and devices for the treatment and prevention of infectious diseases in people of all ages and risk categories. The VTEU network sites must flexible and respond to emerging threats and changing NIAID priorities. To this end, the University of Rochester VTEU (UR VTEU) will collaborate with NIAID and the VTEU leadership group (VTEU LG) to address and prioritize initiatives for infectious diseases such as respiratory, enteric, sexually transmitted infections and antibiotic resistant organisms as well as maintain flexibility to switch focus to emerging threats as the need arises. The University of Rochester is fortunate to enjoy a community with a very positive attitude towards clinical research and collaborative relationships between the major healthcare providers in the city providing access to all the hospitals, clinics and practices in the area. The UR VTEU offers a very experienced administrative and clinical group with a proven track record of successful multicenter clinical trial work. With the support of the VTEU LG, the UR VTEU will be well positioned to develop as well as implement concepts and projects that address important NIAID priorities and formulate best practices, efficiencies and standard operating procedures among VTEU sites. UR VTEU investigators have expertise in adult and pediatric clinical research as well as recruitment of vulnerable populations into clinical trials and thus can anticipate successful recruitment of young and older adults, infants, young children and adolescents, and pregnant women. Additionally, the close relationship of the Monroe County Health Department with the University provides access to patients with sexually transmitted diseases for study participation. We will provide capacity to perform phase 1-3 clinical trials and pharmacokinetic studies as well as surge capacity in terms of personnel and clinical research sites to rapidly respond to urgent NIAID demands. Importantly, our investigators have experience conducting challenge and isolation studies and can provide VTEU facilities for such projects. Our research laboratory expertise will provide the VTEU network with a variety of state of the art technologies to interrogate the host response to infection and immunization as well as develop a deeper understanding of pathogenesis for many infectious diseases. Specifically, core faculty have expertise in a wide range of novel immunologic assays as well as transcriptional and microbiome analysis. In addition, the UR VTEU will provide research opportunities and education for junior faculty to train the next generation of physician scientists. All clinical trials will adhere to NIAID/NIH requirements and comply with Good Clinical Practice. In summary, the UR VTEU site will offer an enthusiastic and diverse group of investigators with a track record of participating in collaborative research and the necessary scientific, clinical, administrative and organizational structure to support NIAID activities."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON","value":18849015,"savings":18849015,"link":null,"description":"UTMB-NOVARTIS ALLIANCE FOR PANDEMIC PREPAREDNESS - OVERALL – ABSTRACT PANDEMIC PREVENTION AND PREPAREDNESS IS A MAJOR SCIENTIFIC AND SOCIETAL PRIORITY THAT REQUIRES SUSTAINED AND FORWARD LOOKING INVESTMENTS ACROSS GOVERNMENTAL, NON-GOVERNMENTAL, ACADEMIC AND PRIVATE SECTORS TO DEVELOP AN ARSENAL OF COUNTERMEASURES AGAINST THE EXISTENTIAL THREAT OF VIRAL PANDEMICS. COMBINING WORLD-LEADING BSL3/4 CAPABILITIES AT UNIVERSITY OF TEXAS OF MEDICAL BRANCH (UTMB) AND STATE-OF-THE ART DRUG DISCOVERY TECHNOLOGIES AT NOVARTIS, THE UTMB NOVARTIS ALLIANCE FOR PANDEMIC PREPAREDNESS (UNAPP), IS A UNIQUE AND INNOVATIVE PARTNERSHIP THAT BRINGS TOGETHER THE MULTI-DISCIPLINARY EXPERTISE REQUIRED TO DELIVER HIGH QUALITY ANTIVIRAL DRUG CANDIDATES. ENABLED BY WORLD-LEADING VIROLOGISTS AND SEASONED DRUG HUNTERS, UNAPP WILL AGGRESSIVELY PROSECUTE A PORTFOLIO OF 5 PROJECTS AIMING TO DISCOVER ORALLY AVAILABLE, SAFE, AND EFFECTIVE DRUGS AGAINST CORONAVIRUSES, FLAVIVIRUS AND HENIPAVIRUS, THREE MAJOR CLASSES OF VIRUSES WITH PANDEMIC POTENTIAL. THE PROJECTS PORTFOLIO COMBINES APPROACHES TARGETING WELL VALIDATED DRUG TARGETS, SUCH AS THE RNA- DEPENDENT RNA POLYMERASES AND VIRAL PROTEASES, AS WELL AS PHENOTYPIC SCREENING, WHICH WILL ALLOW FOR THE DISCOVERY OF CLINICAL DRUG CANDIDATES AND NOVEL TARGETS THAT WILL ADVANCE OUR FUNDAMENTAL UNDERSTANDING OF THE BIOLOGY OF THOSE VIRUSES. FOUR SCIENTIFIC CORES—VIROLOGY, HIGH-THROUGHPUT BIOLOGY, DRUG DISCOVERY AND TRANSLATIONAL RESEARCH CORES—WILL PROVIDE TECHNOLOGICAL AND SCIENTIFIC EXPERTISE TO SUPPORT PROJECT TEAMS AND IMPLEMENT THE SCIENTIFIC STRATEGY TOWARD NOVEL ANTIVIRAL DRUGS. THE UNAPP WILL BE GOVERNED BY AN ADMINISTRATIVE CORE WHICH WILL BE CO-LED BY THE PIS, DR. PEI-YONG SHI AND DR. THIERRY DIAGANA, WHO HAVE A LONG TRACK-RECORD OF SUCCESSFULLY WORKING TOGETHER. BOTH PIS HAVE LED MULTIPLE PRODUCTIVE COLLABORATIONS FOCUSED ON TRANSLATIONAL IMPACT AND COMBINING PUBLIC, PRIVATE AND NON-GOVERNMENTAL ORGANIZATIONS. THE ADMINISTRATIVE CORE WILL PROVIDE INTEGRATED DECISION MAKING IN SCIENTIFIC, OPERATIONAL, FINANCIAL, INTELLECTUAL PROPERTY PROTECTION, AND COMMUNICATION. IN COLLABORATION WITH ALL PROJECT AND CORE LEADERS, AS WELL AS WITH EXTERNAL INPUT FROM A SCIENTIFIC ADVISORY BOARD AND NIH PROGRAM OFFICERS, THEY WILL ENSURE THAT THE PROJECTS PORTFOLIO LEVERAGES THE FULL SPECTRUM OF TECHNOLOGIES AND CAPABILITIES RESIDING IN ALL FOUR SCIENTIFIC CORES, CAPTURING SYNERGIES ACROSS PROJECTS THROUGH CROSS-LEARNING AND EFFICIENT DEPLOYMENT OF PLATFORMS RELEVANT TO MULTIPLE VIRUSES. BECAUSE OF THE UNIQUE COMPLEMENTARITY OF THE SCIENTIFIC CORES AND THE REMARKABLE SYNERGIES OF THE PROJECT PORTFOLIO, WE FULLY EXPECT THAT THE UNAPP WILL YIELD EXCEPTIONAL PRODUCTIVITY AND DELIVER ALL THE PROPOSED OBJECTIVES: (1) DELIVER 3 IND-READY CANDIDATES AND 3 DEVELOPMENT CANDIDATES, (2) ADVANCE ANTIVIRAL RESEARCH, AND (3) TRAIN NEXT-GENERATION DRUG HUNTERS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON","value":56163625,"savings":17314794,"link":null,"description":"UTMB-NOVARTIS ALLIANCE FOR PANDEMIC PREPAREDNESS - OVERALL – ABSTRACT PANDEMIC PREVENTION AND PREPAREDNESS IS A MAJOR SCIENTIFIC AND SOCIETAL PRIORITY THAT REQUIRES SUSTAINED AND FORWARD LOOKING INVESTMENTS ACROSS GOVERNMENTAL, NON-GOVERNMENTAL, ACADEMIC AND PRIVATE SECTORS TO DEVELOP AN ARSENAL OF COUNTERMEASURES AGAINST THE EXISTENTIAL THREAT OF VIRAL PANDEMICS. COMBINING WORLD-LEADING BSL3/4 CAPABILITIES AT UNIVERSITY OF TEXAS OF MEDICAL BRANCH (UTMB) AND STATE-OF-THE ART DRUG DISCOVERY TECHNOLOGIES AT NOVARTIS, THE UTMB NOVARTIS ALLIANCE FOR PANDEMIC PREPAREDNESS (UNAPP), IS A UNIQUE AND INNOVATIVE PARTNERSHIP THAT BRINGS TOGETHER THE MULTI-DISCIPLINARY EXPERTISE REQUIRED TO DELIVER HIGH QUALITY ANTIVIRAL DRUG CANDIDATES. ENABLED BY WORLD-LEADING VIROLOGISTS AND SEASONED DRUG HUNTERS, UNAPP WILL AGGRESSIVELY PROSECUTE A PORTFOLIO OF 5 PROJECTS AIMING TO DISCOVER ORALLY AVAILABLE, SAFE, AND EFFECTIVE DRUGS AGAINST CORONAVIRUSES, FLAVIVIRUS AND HENIPAVIRUS, THREE MAJOR CLASSES OF VIRUSES WITH PANDEMIC POTENTIAL. THE PROJECTS PORTFOLIO COMBINES APPROACHES TARGETING WELL VALIDATED DRUG TARGETS, SUCH AS THE RNA- DEPENDENT RNA POLYMERASES AND VIRAL PROTEASES, AS WELL AS PHENOTYPIC SCREENING, WHICH WILL ALLOW FOR THE DISCOVERY OF CLINICAL DRUG CANDIDATES AND NOVEL TARGETS THAT WILL ADVANCE OUR FUNDAMENTAL UNDERSTANDING OF THE BIOLOGY OF THOSE VIRUSES. FOUR SCIENTIFIC CORES—VIROLOGY, HIGH-THROUGHPUT BIOLOGY, DRUG DISCOVERY AND TRANSLATIONAL RESEARCH CORES—WILL PROVIDE TECHNOLOGICAL AND SCIENTIFIC EXPERTISE TO SUPPORT PROJECT TEAMS AND IMPLEMENT THE SCIENTIFIC STRATEGY TOWARD NOVEL ANTIVIRAL DRUGS. THE UNAPP WILL BE GOVERNED BY AN ADMINISTRATIVE CORE WHICH WILL BE CO-LED BY THE PIS, DR. PEI-YONG SHI AND DR. THIERRY DIAGANA, WHO HAVE A LONG TRACK-RECORD OF SUCCESSFULLY WORKING TOGETHER. BOTH PIS HAVE LED MULTIPLE PRODUCTIVE COLLABORATIONS FOCUSED ON TRANSLATIONAL IMPACT AND COMBINING PUBLIC, PRIVATE AND NON-GOVERNMENTAL ORGANIZATIONS. THE ADMINISTRATIVE CORE WILL PROVIDE INTEGRATED DECISION MAKING IN SCIENTIFIC, OPERATIONAL, FINANCIAL, INTELLECTUAL PROPERTY PROTECTION, AND COMMUNICATION. IN COLLABORATION WITH ALL PROJECT AND CORE LEADERS, AS WELL AS WITH EXTERNAL INPUT FROM A SCIENTIFIC ADVISORY BOARD AND NIH PROGRAM OFFICERS, THEY WILL ENSURE THAT THE PROJECTS PORTFOLIO LEVERAGES THE FULL SPECTRUM OF TECHNOLOGIES AND CAPABILITIES RESIDING IN ALL FOUR SCIENTIFIC CORES, CAPTURING SYNERGIES ACROSS PROJECTS THROUGH CROSS-LEARNING AND EFFICIENT DEPLOYMENT OF PLATFORMS RELEVANT TO MULTIPLE VIRUSES. BECAUSE OF THE UNIQUE COMPLEMENTARITY OF THE SCIENTIFIC CORES AND THE REMARKABLE SYNERGIES OF THE PROJECT PORTFOLIO, WE FULLY EXPECT THAT THE UNAPP WILL YIELD EXCEPTIONAL PRODUCTIVITY AND DELIVER ALL THE PROPOSED OBJECTIVES: (1) DELIVER 3 IND-READY CANDIDATES AND 3 DEVELOPMENT CANDIDATES, (2) ADVANCE ANTIVIRAL RESEARCH, AND (3) TRAIN NEXT-GENERATION DRUG HUNTERS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON","value":7131815,"savings":1671714,"link":null,"description":"PANDEMIC PREPAREDNESS: BIOCONTAINMENT FACILITY UPGRADE AND INTEGRATION AT UTMB/GALVESTON NATIONAL LABORATORY - PROJECT SUMMARY/ABSTRACT TOWARD MAINTAINING AND IMPROVING PANDEMIC PREPAREDNESS, WE PROPOSE VALUE-ADDED FACILITY UPGRADES THAT BETTER INTEGRATE THE HIGH-CONTAINMENT COMMUNITIES AT THE UNIVERSITY OF TEXAS MEDICAL BRANCH (UTMB), GALVESTON. UTMB LABORATORIES INTEGRATE OPERATIONS THROUGH JOINT-FACILITY MANAGEMENT, USAGE, AND COLLABORATIONS THAT INCLUDE EDUCATING THE NEXT GENERATION OF RESEARCH SCIENTISTS AND MEDICAL STAFF. THE UTMB COMMUNITY CONTAINS THE ROBERT E. SHOPE LABORATORY (SHOPE)—THE FIRST FULL-SIZED BSL-4 FACILITY WITHIN A UNIVERSITY IN THE UNITED STATES, A STRUCTURALLY SEPARATE HIGH-CONTAINMENT GALVESTON NATIONAL LABORATORY (GNL), AND BSL3 LABORATORIES OF MARY MOODY NORTHEN PAVILION (MMNP). EACH FACILITY SUPPORTS MULTIPLE EXPERIENCED, PUBLISHED, AND GOVERNMENTALLY-FUNDED INVESTIGATORS RESEARCHING PATHOGENS WITH PANDEMIC POTENTIAL, AS WELL AS FACILITATING BIOMEDICAL RESEARCH OF VACCINES AND THERAPEUTICS. OUR CORPUS OF RESEARCHERS INCLUDES 31 EXPERTS IN ONE OR MORE OF SIX OUT OF THE SEVEN RNA VIRUSES OF FOCUS BY NIAID TOWARD PANDEMIC PREPAREDNESS. THE REQUESTED FINANCIAL SUPPORT WILL ENHANCE FACILITY CAPABILITIES AND SECURITY WITHIN AN INTEGRATED SYSTEM OF SERVICES AND OPERATIONAL FUNCTIONS THAT SUPPORT THE MANDATE OF THE GNL WITHIN THE UTMB HIGH-CONTAINMENT COMMUNITY. WE PROPOSE TO ENHANCE INTEGRATION OF SYSTEMS TO PROVIDE A COMPREHENSIVE PROTECTION OF ALL UTMB HIGH-CONTAINMENT FACILITIES AGAINST CYBERATTACK, WHILE IMPROVING WORKFLOW, BIOSAFETY, BIOSECURITY, AND TRAINING CAPACITIES THROUGH MODERNIZATION OF SPECIFIC ANTIQUATED HIGH-CONTAINMENT AREAS THAT ARE ALSO ESSENTIAL TO PANDEMIC RESPONSIVITY. OF PRIORITY IS TO UPGRADE EQUIPMENT AND SUPPORTIVE INFRASTRUCTURE UTILIZED IN HIGH-CONTAINMENT RNA VIRAL RESEARCH REACHING “END-OF-LIFE” (EOL) OR “END-OF-SERVICE” (EOS), PRIOR TO EXPERIENCING DIFFICULTIES PROCURING PARTS OR HAVING STOPPAGE RESULTING IN LOST TIME, FUNDS, AND MITIGATING PREPAREDNESS. ADDITIONALLY, WE WILL REMEDY SPECIFIC INFRASTRUCTURAL SHORTCOMINGS TO IMPROVE FACILITY OPERATIONS. FURTHERMORE, AS A LEADER IN TEACHING THE FUTURE INVESTIGATORS OF HIGH-CONSEQUENCE PATHOGENS, THE GNL PROPOSES TO UPGRADE A TRAINING AREA TO BETTER REFLECT THE ACTUAL BSL4 ENVIRONMENT. WE WILL MEET THESE GOALS THROUGH THREE AIMS: AIM 1: INTEGRATE CYBERSECURITY SYSTEMS UNDER THE GNL ISOLATED PROTECTION, WHILE MODERNIZING SAFETY AND SECURITY OF VIRTUAL AND PHYSICAL STRUCTURES OF UTMB HIGH-CONTAINMENT FACILITIES. AIM 2: MODERNIZE FACILITY AND EQUIPMENT OF INTEGRATED USAGE AMONG UTMB’S RESEARCH COMMUNITY DIRECTLY IN SUPPORT OF BSL3 AND BSL4 RNA RESEARCH OF VIRUSES WITH HIGH PANDEMIC OR WEAPONIZATION POTENTIAL. AIM 3: IMPLEMENT PANDEMIC PREPAREDNESS TOWARD EFFECTIVE FUTURE STRATEGIC RESPONSE CAPACITY. ULTIMATELY, MODERNIZATIONS AND INTEGRATIONS OF SYSTEMS, OPERATIONS, AND TRAINING WILL BETTER POSITION UTMB TO CONTRIBUTE AS A GLOBAL RESEARCH LEADER IN DISCOVERY AND DEVELOPMENT OF SOLUTIONS AGAINST HIGH- CONSEQUENCE PATHOGENS. THIS PROPOSAL IS FRAMED TO PROVIDE ENHANCED SECURITY AND CAPACITIES TO FURTHER SUPPORT OUR ROLES AS COLLABORATOR, REFERENCE CENTER AND REPOSITORY, INSTITUTIONAL MODEL, AND TRAINER TOWARD STRATEGIC IMPLEMENTATION OF A GLOBAL PANDEMIC PREPAREDNESS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON","value":4078198.87,"savings":1142720,"link":null,"description":"WORLD REFERENCE CENTER FOR EMERGING VIRUSES AND ARBOVIRUSES (WRCEVA)"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF WASHINGTON","value":5394452,"savings":1295382,"link":null,"description":"The proposed University of Washington (UW) Vaccine and Treatment Evaluation Unit (VTEU) will be led by highly experienced investigators in domestic and international clinical trials, and supported by a Steering Committee that includes leading experts in the areas of focus of this application, including respiratory infections, sexually transmitted infections, malaria challenge studies, enteric infections and other neglected tropical diseases. The co-Principal Investigators have conducted >30 clinical trials, most under IND; these include trials sponsored by NIAID, including VTEU contracts, HPTN and STI CTG, industry sponsors, and investigator-held IND. The proposed VTEU Research Clinic at Harborview Medical Center has been conducting clinical trials for several decades, and the recruitment, enrollment, and retention practices and policies have been well established. Our strong record in obtaining research funding has resulted in the UW School of Medicine providing ample space that has been specifically designed to accommodate clinical trials conducted in the area of Infectious Diseases. The UW VTEU will leverage the extraordinary breadth and depth of expertise, facilities, resources, populations, and geographic reach of the UW and our collaborating institutions. Locally, these include Seattle Children’s and the Fred Hutchinson Cancer Research Center, in addition to several campus locations for UW Medicine. Internationally, the investigators included in the UW VTEU also lead well-established and experienced research sites with outstanding infrastructure in Kenya (UW- Kenya and the Kenya Medical Research Institute), South Africa (University of Witwatersrand), and Peru (Asociación Civil Selva Amazónica). Both domestic and international investigators have vast experience in the conduct of clinical trials of vaccines and other therapeutics under IND, with many sponsored by NIAID. This consortium has demonstrated capacity to recruit and retain the populations targeted by the VTEUs, including healthy volunteers, pregnant women, children, persons with or at risk for sexually transmitted infections, and participants in human challenge studies. The Specific Aims of the UW VTEU are: 1. Recruit a wide range of participants in clinical trials approved by the Leadership Group; 2. Implement clinical trials in compliance with Good Clinical Practice Guidelines and other regulatory guidance; 3. Ensure participant safety and monitor trials for adverse events; 4. Support the Leadership Group in the development of clinical protocols, providing unique clinical and research laboratory capabilities, performing data analysis, and reporting the results of clinical trials; 5. Provide outstanding training opportunities and mentorship to early stage investigators who desire to gain experience in conducting clinical trials."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF WASHINGTON","value":9616028,"savings":921717,"link":null,"description":"The proposed University of Washington (UW) Vaccine and Treatment Evaluation Unit (VTEU) will be led by highly experienced investigators in domestic and international clinical trials, and supported by a Steering Committee that includes leading experts in the areas of focus of this application, including respiratory infections, sexually transmitted infections, malaria challenge studies, enteric infections and other neglected tropical diseases. The co-Principal Investigators have conducted >30 clinical trials, most under IND; these include trials sponsored by NIAID, including VTEU contracts, HPTN and STI CTG, industry sponsors, and investigator-held IND. The proposed VTEU Research Clinic at Harborview Medical Center has been conducting clinical trials for several decades, and the recruitment, enrollment, and retention practices and policies have been well established. Our strong record in obtaining research funding has resulted in the UW School of Medicine providing ample space that has been specifically designed to accommodate clinical trials conducted in the area of Infectious Diseases. The UW VTEU will leverage the extraordinary breadth and depth of expertise, facilities, resources, populations, and geographic reach of the UW and our collaborating institutions. Locally, these include Seattle Children’s and the Fred Hutchinson Cancer Research Center, in addition to several campus locations for UW Medicine. Internationally, the investigators included in the UW VTEU also lead well-established and experienced research sites with outstanding infrastructure in Kenya (UW- Kenya and the Kenya Medical Research Institute), South Africa (University of Witwatersrand), and Peru (Asociación Civil Selva Amazónica). Both domestic and international investigators have vast experience in the conduct of clinical trials of vaccines and other therapeutics under IND, with many sponsored by NIAID. This consortium has demonstrated capacity to recruit and retain the populations targeted by the VTEUs, including healthy volunteers, pregnant women, children, persons with or at risk for sexually transmitted infections, and participants in human challenge studies. The Specific Aims of the UW VTEU are: 1. Recruit a wide range of participants in clinical trials approved by the Leadership Group; 2. Implement clinical trials in compliance with Good Clinical Practice Guidelines and other regulatory guidance; 3. Ensure participant safety and monitor trials for adverse events; 4. Support the Leadership Group in the development of clinical protocols, providing unique clinical and research laboratory capabilities, performing data analysis, and reporting the results of clinical trials; 5. Provide outstanding training opportunities and mentorship to early stage investigators who desire to gain experience in conducting clinical trials."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF WASHINGTON","value":1561928,"savings":684966,"link":null,"description":"The proposed University of Washington (UW) Vaccine and Treatment Evaluation Unit (VTEU) will be led by highly experienced investigators in domestic and international clinical trials, and supported by a Steering Committee that includes leading experts in the areas of focus of this application, including respiratory infections, sexually transmitted infections, malaria challenge studies, enteric infections and other neglected tropical diseases. The co-Principal Investigators have conducted >30 clinical trials, most under IND; these include trials sponsored by NIAID, including VTEU contracts, HPTN and STI CTG, industry sponsors, and investigator-held IND. The proposed VTEU Research Clinic at Harborview Medical Center has been conducting clinical trials for several decades, and the recruitment, enrollment, and retention practices and policies have been well established. Our strong record in obtaining research funding has resulted in the UW School of Medicine providing ample space that has been specifically designed to accommodate clinical trials conducted in the area of Infectious Diseases. The UW VTEU will leverage the extraordinary breadth and depth of expertise, facilities, resources, populations, and geographic reach of the UW and our collaborating institutions. Locally, these include Seattle Children’s and the Fred Hutchinson Cancer Research Center, in addition to several campus locations for UW Medicine. Internationally, the investigators included in the UW VTEU also lead well-established and experienced research sites with outstanding infrastructure in Kenya (UW- Kenya and the Kenya Medical Research Institute), South Africa (University of Witwatersrand), and Peru (Asociación Civil Selva Amazónica). Both domestic and international investigators have vast experience in the conduct of clinical trials of vaccines and other therapeutics under IND, with many sponsored by NIAID. This consortium has demonstrated capacity to recruit and retain the populations targeted by the VTEUs, including healthy volunteers, pregnant women, children, persons with or at risk for sexually transmitted infections, and participants in human challenge studies. The Specific Aims of the UW VTEU are: 1. Recruit a wide range of participants in clinical trials approved by the Leadership Group; 2. Implement clinical trials in compliance with Good Clinical Practice Guidelines and other regulatory guidance; 3. Ensure participant safety and monitor trials for adverse events; 4. Support the Leadership Group in the development of clinical protocols, providing unique clinical and research laboratory capabilities, performing data analysis, and reporting the results of clinical trials; 5. Provide outstanding training opportunities and mentorship to early stage investigators who desire to gain experience in conducting clinical trials."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS","value":4618169,"savings":4618169,"link":null,"description":"PANCORVAC (CENTER FOR PAN-CORONAVIRUS VACCINE DEVELOPMENT) - SUMMARY  MOST OF THE VACCINES CURRENTLY APPROVED OR IN DEVELOPMENT AGAINST THE PANDEMIC SARS-COV-2 (SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2) VIRUS TARGET IMMUNODOMINANT, STRAIN-SPECIFIC EPITOPES IN THE SARS-COV-2 SPIKE (S) PROTEIN AND ARE THEREFORE NOT EXPECTED TO CONFER PROTECTION AGAINST OTHER CORONAVIRUSES. ACCORDINGLY, THE NIAID ANNOUNCED NOT-AI-21-002, WHICH CALLS FOR THE “DEVELOPMENT OF PROPHYLACTIC VACCINES TO PROVIDE BROAD AND DURABLE PROTECTION AGAINST CORONAVIRUSES, ESPECIALLY SARS-COV-2 AND OTHERS WITH PANDEMIC POTENTIAL”. IN RESPONSE TO THIS CALL, WE ASSEMBLED THE PAN-CORONAVIRUS VACCINE (PANCOVAC) CONSORTIUM TO DEVELOP AND TEST NOVEL PAN-CORONAVIRUS VACCINES. RESEARCH PROJECT 1 (RP1; DESIGN AND EVALUATION OF PAN- COV VACCINES) USES TWO STRATEGIES TO DEVELOP BROADLY PROTECTIVE CORONAVIRUS VACCINES: (I) FOCUS IMMUNE RESPONSES AWAY FROM THE IMMUNODOMINANT EPITOPES IN THE HEAD REGION OF S AND TOWARDS THE MORE CONSERVED, IMMUNE-SUBDOMINANT EPITOPES IN THE STEM REGION OF S; AND (II) REFOCUS IMMUNE RESPONSES FROM THE VARIABLE IMMUNODOMINANT EPITOPES TOWARDS MORE CONSERVED EPITOPES IN THE HEAD REGION OF S. FOR EACH STRATEGY, SEVERAL INNOVATIVE APPROACHES WILL BE USED. NOVEL ANTIGENS WILL BE PRESENTED BY VIRUS-LIKE PARTICLES BASED ON A SELF- ASSEMBLING BACTERIOPHAGE COAT PROTEIN (A HIGHLY IMMUNOGENIC PLATFORM). THE CANDIDATE VACCINES WILL BE TESTED FOR THEIR IMMUNOGENICITY AND PROTECTIVE EFFICACY AGAINST DIFFERENT CORONAVIRUSES IN AN ANIMAL MODEL. SELECTED CANDIDATES WILL BE TESTED IN A SECOND ANIMAL MODEL, AND WITH AN MRNA LIPID NANOPARTICLE PLATFORM. ADDITIONAL STUDIES WILL TEST THE DURABILITY OF IMMUNE RESPONSES AND THE EFFECT OF VACCINATION ON VIRUS TRANSMISSION. SAMPLES FROM VACCINATED ANIMALS WILL BE PROVIDED TO RESEARCH PROJECT 2 (RP2; IMMUNOLOGICAL RESPONSES TO PAN-COV VACCINES) FOR A DETAILED ASSESSMENT OF B- AND T-CELL RESPONSES. FIRST, RP2 WILL CONTINUE ITS ONGOING EFFORTS TO GENERATE AND CHARACTERIZE PANELS OF SARS-COV S-SPECIFIC MABS, WHICH WILL BE USED IN RP1 TO HELP CHARACTERIZE AND PRIORITIZE VACCINE CANDIDATES. MOREOVER, “IG-OMICS”, WHICH INVOLVES SINGLE-CELL TECHNOLOGIES ALLOWING HIGH- THROUGHPUT ANALYSIS OF B-CELL RESPONSES, PHENOTYPES, IMMUNOGLOBULIN (IG) REPERTOIRES AND MABS THAT REACT TO SEVERAL CORONAVIRUSES (A TECHNOLOGY DEVELOPED BY ONE OF THE RP2 INVESTIGATORS), WILL BE USED TO CHARACTERIZE B CELL-MEDIATED IMMUNITY AND MAB SPECIFICITY INDUCED BY THE CANDIDATE VACCINES. RP2 WILL ALSO TEST (AND COMPARE WITH DATA FROM A HUMAN COHORT STUDY) THE ABILITY OF THE CANDIDATE VACCINES TO ELICIT RESPONSES TO CROSS-REACTIVE CD4 AND CD8 T CELL EPITOPES. IN PARTICULAR, RECENTLY DEVELOPED NOVEL METHODS WILL BE USED TO CHARACTERIZE AND COMPARE THE T-CELL REPERTOIRES UPON INFECTION AND VACCINATION. AN ADMINISTRATIVE CORE WILL OVERSEE AND MANAGE ALL FINANCIAL AND ADMINISTRATIVE ASPECTS OF THE CONSORTIUM. OUR PROPOSED RESEARCH DRAWS STRENGTH FROM A MULTI- INSTITUTIONAL TEAM OF EXPERTS IN MOLECULAR VIROLOGY, STRUCTURAL BIOLOGY, NANOBIOTECHNOLOGY, AND B- AND T-CELL IMMUNOLOGY."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS","value":1738787,"savings":162938,"link":null,"description":"CORONAVIRUS RNA SYNTHESIS BY MULTICOMPONENT PROTEIN MACHINES"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"VANDERBILT UNIVERSITY MEDICAL CENTER","value":27356563,"savings":4396988,"link":null,"description":"ABSTRACT The goal of this UM1 proposal is to use the remarkable research infrastructure at Vanderbilt University Medical Center and collaborating sites (Washington University, University of Pittsburgh, and University of Pennsylvania) to conceptualize, design, implement, and analyze clinical research studies across a wide variety of pathogens, infectious diseases, and populations as a Vaccine and Treatment Evaluation Unit (VTEU). Vanderbilt University Medical Center was among the first VTEUs funded and has led pivotal studies of influenza, pertussis, pneumococcus, smallpox, and malaria vaccines. The Vanderbilt VTEU has a proven capacity to enroll healthy populations rapidly, including participating in two NIH- directed influenza pandemic responses since 2009, as well as expertise enrolling special populations such as pregnant women, infants and children, adults with underlying medical comorbidities, and the elderly. In the current application, we have expanded our ability to recruit across the lifespan and across multiple pathogens, including increased expertise in sexually transmitted infections, malaria, and novel approaches to conducting clinical trial visits in the home setting. The Vanderbilt VTEU has also led efforts to train the next generation of vaccinologists and clinical trial experts in infectious diseases, including the development of a vaccinology fellowship, participation of fellows and junior faculty in protocol teams and data safety committees, and encouraging concept development by junior faculty. The Vanderbilt VTEU is also committed to working collaboratively with the newly formed Infectious Diseases Leadership Group to articulate priorities for ID research."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"WASHINGTON UNIVERSITY","value":1955860,"savings":142285,"link":null,"description":"Project Summary/Abstract This R01 entitled, “Development and characterization of engineered therapeutic antibodies against SARS-CoV- 2”, builds on our project infrastructure, expertise, and experience in characterizing viral-host factor interactions in negative strand RNA viruses. Since originating in China, SARS-CoV-2 has since rapidly spread and is now a global pandemic. Significant concerns are that humans are immunologically naïve, and there are no available therapies. In the US, the disease has already overwhelmed the healthcare system in some states and have a serious knock-on effect in exacerbating the standard of care for other diseases. At the time of writing, nearly 5 million cases and >160,000 deaths have been attributed to COVID-19. The virus replicates in the lungs and causes a severe respiratory disease, COVID-19, which is fatal in >2% of cases. Neutralizing antibodies (nAbs) generated by natural infection or vaccines is known to control many infections and early studies in the current COVID-19 pandemic, including studies to test convalescent plasma treatments, are promising. These studies highlight the potential significance of nAb-based therapy. While IgG format of nAbs have long been the most extensively used format, early studies, including our own suggest that additional multivalent formats of nAbs may be more effective. This provides an innovative method to develop nAbs while acquiring potential benefits from effective neutralization at lower doses and lower likelihood of the emergence of resistance mutants. SARS-CoV- 2 is a single stranded, non-segmented, enveloped RNA virus. Viral infection requires interaction of the spike glycoprotein receptor binding domain (RBD) to the host receptor ACE2. Here, we will build on newly developed and established approaches that have been optimized through our work other systems to generate antibodies targeting spike and spike RBD using phage display technology and characterize their physical properties. We will engineer antibodies with increased valency and test for potency in in vitro neutralization assays and in vivo efficacy in a mouse model. At the completion, we expect to provide innovative and unique multivalent nAb leads with unique characteristics that will rival the best in class IgG drugs."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"WESTAT, INC","value":4000000,"savings":4000000,"link":null,"description":"Over the past three decades, there have been alarming upward trends in the rates of maternal morbidity and mortality in the United States. Overall, the identified clinical causes of maternal death are: cardiovascular conditions (14%), hemorrhage (13%), infection (11%) embolism (10%), cardiomyopathy (95), mental health conditions (9%) and preeclampsia/eclampsia (8%) but these conditions vary by race/ethnicity. For Black, non-Hispanic women, the two leading causes of death were cardiomyopathy and cardiovascular conditions, and mental conditions was the leading cause among White, non-Hispanic women.1 Obesity, hypertension, smoking, opioid use and sleep disorders are also conditions and behaviors that have been found to be associated with maternal morbidity such as hemorrhage, preeclampsia and cardiomyopathy. These could potentially be addressed in primary care before and between pregnancies.2-6 The National Heart, Lung Blood Institute (NHLBI) is participating in a trans-National Institutes of Health (NIH) effort to improve women’s health, particularly maternal morbidity and mortality. A plan – Advancing Science for the Health of Women, The Trans-NIH Strategic Plan for Women’s Health Research – was developed for the period 2019 – 2023. This plan provides a framework that recognizes the complex interactions of multiple factors that affect women’s health across the life course, including pregnancy. Life course theory posits that health development begins before conception and continues across the life span. It suggests that a complex play of biologic, behavioral, psychological, and social protective and risk factors contribute to health outcomes, and that health status reflects the cumulative lifetime exposure to these factors. The guiding principles for this plan are consideration of the complex factors affecting women’s health, the inclusion of diverse populations that are disproportionately affected by morbidity and mortality, and active engagement of a diverse group of scientists.7 The NIH approach to reducing maternal morbidity and mortality will aim to enhance health disparities research, increase the understanding of social determinants and other risk factors (including environmental risk factors), improve care (antepartum, intrapartum and postpartum) and management, provide insight to psychological exposures such as stress, discrimination and caregiving, understand coping behaviors in families affected by maternal morbidity or mortality, and investigate the role of implicit bias in the health care systems regarding pregnancy.8 Within NHLBI, maternal and women’s health priorities span all of the objectives of the NHLBI strategic vision, and NHLBI has supported a number of maternal health programs looking at hypertension, sleep disorders, and other pregnancy complications including pre-eclampsia, eclampsia, and gestational diabetes. The goal of the NHLBI 3M Administrative Coordinating Center (3M ACC) is to engage communities and networks in areas that experience high levels of maternal morbidity and mortality. The 3M ACC will support the preliminary work necessary to identify and prepare a group of community-based organizations to respond to future funding opportunities. The 3M ACC will develop the infrastructure to support this group of Maternal Morbidity and Mortality Regional Coalitions (3M RCs) and provide scientific support and coordination to NHLBI on emerging scientific needs. Specifically, the 3M ACC will support these programmatic objectives: • Identify research groups and organizations with existing and relevant expertise and community partnerships. • Conduct landscape analyses and community-informed needs assessments. • Identify within each community implementation opportunities and barriers to improve delivery of evidence-based care to reduce maternal morbidity and mortality. • Develop and conduct early-stage tests of implementation approaches to identify potential strategies to ensure the proposed approaches a"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"YALE UNIVERSITY","value":1671288,"savings":271887,"link":null,"description":"VIRAL AND IMMUNE-MEDIATED CNS PATHOLOGY DURING SARS-COV-2 INFECTION"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"YALE UNIVERSITY","value":7002260,"savings":200511,"link":null,"description":"The overall goal of the Human Immunology Project Consortium (HIPC) program is to capitalize on recent advances in immune profiling methods in order to create a novel public resource that characterizes diverse states of the human immune system. We propose to contribute to this program through deep interrogation and a broad systems approach that will identify molecular signatures of divergent human immune responses to infections. The three projects that comprise our U19 each leverage a common experimental infrastructure to focus on a different infectious diseases: the Lyme disease spirochete Borrelia burgdorferi, emerging arthropod-borne West Nile virus, and effects of aging on vaccination against influenza. Our goal is to delineate human immune signatures that are associated with the divergent manifestations in the population, using well-defined patient cohorts and a multidimensional analytical approach to quantitatively assess primary human immune cell function. Our program employs cutting-edge immune profiling such as multidimensional profiling by CyTOF, metabolomics, nanoscale technologies such as MuSIC (MultiSpectral Imaging Cytometry), and RNA-seq on single cells that will inform a systems approach to elucidate the biologic signatures defining immune responsiveness. Commonalities between the responses in different tissues, and to the different infection types, will be determined by quantifying signature enrichments, and by identifying conserved active sub-networks in this immune-specific functional network. This collaborative U19 takes advantage of enormous strengths across our institutions to tackle a challenging issue in human immunology. The investigators in this proposal have established collaborations, regular interactions, and a track record of shared success. Our three research projects are supported by shared cores for Administration, Data Management and Analysis, Single Cell Immunophenotyping, and Clinical Recruitment. The united goal of these varied approaches is to define elements of the immune response that contribute to divergent infection outcomes. This multifactorial, wide-angle view of the immune response will be compiled employing the expertise of each individual approach for Systems Modeling from deep interrogation of three sets of stratified patient cohorts. The output of this functional systems immunology approach will be definitions of human immune signatures following multiple forms of infectious challenges with the ultimate goal of defining future targets for intervention and predicting susceptibility or resistance."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"BETH ISRAEL HOSPITAL","value":897731,"savings":377172,"link":null,"description":"IMMUNOLOGIC SIGNATURES OF SARS-COV-2 VACCINATION AND DISEASE"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"BRIGHAM & WOMEN`S HOSPITAL","value":3672336,"savings":2093082,"link":null,"description":"COVID-19 is a US and global disaster which has led to the deaths of almost a million individuals, including over 203,000 Americans, thus far. COVID-19 is caused by a novel beta-coronavirus (CoV) known as Severe Acute Respiratory Syndrome (SARS)-CoV-2, which was reported to cause severe pneumonia and lethal respiratory failure. Little is known about the disease mechanism of this virus and its disease mechanism. In this application, we propose to test the effects of SARS-CoV-2 on the brain. We will develop multiple cell-type specific mouse models that express the SARS-CoV-2 receptor, human ACE2, in a cell-type specific manner. We will then use a variety of molecular, biochemical, histological and neuroscience approaches to test the brain tropism of SARS-CoV-2 in depth and the effects of that on the central regulation of respiration. This proposal will have a transformative impact on our current understanding of COVID- 19 and its mechanisms of pathogenesis and will uncover important therapeutic targets."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"CASE WESTERN RESERVE UNIVERSITY","value":806907,"savings":298683,"link":null,"description":"PRE-EXPOSURE IMMUNOLOGIC HEALTH AND LINKAGES TO SARS-COV2 SEROLOGIC RESPONSES, ENDOTHELIAL CELL RESILIENCE, AND CARDIOVASCULAR COMPLICATIONS: DEFINING THE MECHANISTIC BASIS OF HIGH RISK ENDOTYPES."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"CEDARS-SINAI MEDICAL CENTER","value":2652785.13,"savings":477912,"link":null,"description":"ASBTRACT Overview Every day, Californians continue to experience high levels of exposure to the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) virus. There is an ever-growing urgent need to better understand the nature of exposures, course of illness and recovery, and potential for immunity among persons at particularly heightened risk for the worst COVID-19 outcomes. As part of a rapid scientific response to the present public health crisis, we convened on March 18, 2020 a collaborative of frontline clinicians and scientists to form the Coronavirus Risk Associations and Longitudinal Evaluation (CORALE) studies (corale-study.org). We established two base study cohorts with enrollment centered on (i) patients with suspected or confirmed COVID-19 treated in our health system (currently N>8,300) and on (ii) healthcare workers directly or indirectly involved in delivering their care (currently N=6,679). In response to NIH RFA-CA-20-038, we are now highly motivated and prepared to leverage our existing infrastructure to directly address the critical need for comprehensive longitudinal data collection and analyses to advanced our understanding of SARS-CoV-2 risks, the course of disease, the nature of recovery, and the potential for immunity across populations at risk. By establishing the CORALE-SeroNet U54 program, our goal will be to form a robust and sustainable structure of academic activities centered on investigating the responses elicited by SARS-CoV-2 exposure and the extent to which carefully phenotyped clinical and molecular profiles can signal robust immune reconstitution and complete functional recovery. Our study will be centered on the ethnically/racially diverse population served by our health system in Los Angeles, given then critical need for more knowledge regarding the determinants of COVID-19 related risks in these minority subgroups. Our scientific objectives will be achieved by an outstanding collaborative team of clinician-scientists, epidemiologists, immunologists, basic and translational scientists, analytical chemists, and biostatisticians. Leveraging our collective experience, resources, and infrastructure at major academic institutions from across Southern California (Cedars Sinai, UCSD, UCLA, and USC), we will advance the scientific enterprise through the three distinct yet closely integrated research Projects: Project 1 will elucidate the natural history and longitudinal trajectories that represent the diversity of SARS-CoV-2 exposure, infection, recovery, and clinical immunity patterns across the spectrum of persons at risk. Project 2 will investigate the determinants of SARS-CoV-2 response in persons with altered innate immune function, with a focus on individuals with pre-infection susceptibility traits (e.g. metabolic disease states); and, Project 3 will investigate the determinants of SARS- CoV-2 response in persons with altered adaptive immune function, with a focus on individuals with immune- altered status arising from select malignancies, autoimmune disease, and/or their directed therapies. As a whole this research program will integrate population, clinical, translational, and basic science resources with a world- class investigator team to meet the urgent need for new mechanistic insights and therapeutic approaches to address key knowledge gaps regarding SARS-CoV-2 susceptibility and potential for immunity."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"Duke University","value":86836635,"savings":7524803,"link":null,"description":"ABSTRACT There is an urgent need to reduce disparities in COVID-19 associated morbidity and mortality outcomes in historically marginalized and vulnerable populations disproportionately affected by the COVID-19 pandemic. To address this need the Rapid Acceleration of Diagnostics for Underserved Populations (RADx-UP) program will support Community-Engaged Testing Research Projects and Social, Ethical and Behavioral Implications (SEBI) Research Projects to understand SARS-CoV-2 infection patterns and increase access and effectiveness of diagnostic methods in underserved and/or vulnerable populations. The Duke Clinical Research Institute (DCRI), the UNC Center for Health Equity Research (CHER), and Community-Campus Partnerships for Health (CCPH) propose to serve as the Coordination and Data Collection Center (CDCC) to provide management, direction, and overall coordination of the RADx-UP consortium. Together, our multidisciplinary experience in project coordination; COVID-19 thought leadership; regulatory science; community engagement; health equity research; social justice; adult and child research; statistics; data science; and clinical research informatics will advance the objectives of the projects in the RADx-UP Program. Our overarching goal is to implement a community-centered approach and establish an effective, flexible, participatory, and sustainable CDCC that will serve as the infrastructure to maximize the community impact of projects in the RADx-UP Program. To achieve this vision, we will establish a program framework comprised of four cores. Our Administration and Coordination Core, in collaboration with NIH scientific staff, will facilitate the work of the RADx-UP Program in overarching administrative management. The COVID-19 Testing Core will advise and guide COVID-19 testing protocols; curate emergent testing data; and administer the Rapid Pilot Studies Program. The Community and Health System Engagement Core will support a community of practice across the RADx-UP Program; provide support in exchanging best practices across communities on recruitment, engagement, and retention of study participants; and coordinate the dissemination of study findings from RADx-UP projects. The Data Science and Biostatistics Core will manage data collection, integration, and sharing for the RADx-UP Program including merging and harmonization of multiple and diverse data sources and provide data standards, data collection design, and biostatistics consulting services. The RADx-UP CDCC goals will be met using established infrastructure and subject matter experts and will be customized to meet the variable needs of the RADx-UP community. Using the highest research standards, our team will accomplish the goals set out by the NIH in managing this critically important collaborative effort."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"Duke University","value":2000000,"savings":982383,"link":null,"description":"ABSTRACT There is an urgent need to reduce disparities in COVID-19 associated morbidity and mortality outcomes in historically marginalized and vulnerable populations disproportionately affected by the COVID-19 pandemic. To address this need the Rapid Acceleration of Diagnostics for Underserved Populations (RADx-UP) program will support Community-Engaged Testing Research Projects and Social, Ethical and Behavioral Implications (SEBI) Research Projects to understand SARS-CoV-2 infection patterns and increase access and effectiveness of diagnostic methods in underserved and/or vulnerable populations. The Duke Clinical Research Institute (DCRI), the UNC Center for Health Equity Research (CHER), and Community-Campus Partnerships for Health (CCPH) propose to serve as the Coordination and Data Collection Center (CDCC) to provide management, direction, and overall coordination of the RADx-UP consortium. Together, our multidisciplinary experience in project coordination; COVID-19 thought leadership; regulatory science; community engagement; health equity research; social justice; adult and child research; statistics; data science; and clinical research informatics will advance the objectives of the projects in the RADx-UP Program. Our overarching goal is to implement a community-centered approach and establish an effective, flexible, participatory, and sustainable CDCC that will serve as the infrastructure to maximize the community impact of projects in the RADx-UP Program. To achieve this vision, we will establish a program framework comprised of four cores. Our Administration and Coordination Core, in collaboration with NIH scientific staff, will facilitate the work of the RADx-UP Program in overarching administrative management. The COVID-19 Testing Core will advise and guide COVID-19 testing protocols; curate emergent testing data; and administer the Rapid Pilot Studies Program. The Community and Health System Engagement Core will support a community of practice across the RADx-UP Program; provide support in exchanging best practices across communities on recruitment, engagement, and retention of study participants; and coordinate the dissemination of study findings from RADx-UP projects. The Data Science and Biostatistics Core will manage data collection, integration, and sharing for the RADx-UP Program including merging and harmonization of multiple and diverse data sources and provide data standards, data collection design, and biostatistics consulting services. The RADx-UP CDCC goals will be met using established infrastructure and subject matter experts and will be customized to meet the variable needs of the RADx-UP community. Using the highest research standards, our team will accomplish the goals set out by the NIH in managing this critically important collaborative effort."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"EMORY UNIVERSITY","value":3057531,"savings":489501,"link":null,"description":"IMMUNE REGULATION OF COVID-19 INFECTION IN CANCER AND AUTOIMMUNITY"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"EMORY UNIVERSITY","value":2146671,"savings":331941,"link":null,"description":"AN ADAPTIVE INTERVENTION TRIAL OF HOME TESTING WITH BEHAVIORAL NUDGES FOR IMPROVING COVID-19 TESTING AND PREVENTION AMONG PEOPLE AFFECTED BY DIABETES - ABSTRACT THIS MULTI-INSTITUTION TEAM (EMORY UNIVERSITY, MOREHOUSE SCHOOL OF MEDICINE, GEORGIA INSTITUTE OF TECHNOLOGY), ANCHORED BY THE GEORGIA CENTER FOR DIABETES TRANSLATION RESEARCH (P30DK111024) PARTNERSHIP, PROPOSES TO LEVERAGE AND EXPAND ON THE ON-GOING, RADX-UP FUNDED PROJECT PEACH (P30DK111024), TO DESIGN AND EVALUATE A HOME-BASED COVID-19 TESTING PROGRAM WITH BEHAVIORAL NUDGES DELIVERED VIA MOBILE PHONE TEXTS TO INCREASE UPTAKE OF COVID-19 PREVENTION ACTIVITIES (TESTING, VACCINATION, PREVENTIVE BEHAVIORS) IN “AN ADAPTIVE INTERVENTION TRIAL OF HOME TESTING WITH BEHAVIORAL NUDGES FOR IMPROVING COVID-19 TESTING AND PREVENTION AMONG PEOPLE AFFECTED BY DIABETES.” COVID-19 TESTING REMAINS A CORNERSTONE IN UNDERSTANDING AND MANAGING THE COVID-19 PANDEMIC. THE STATE OF GEORGIA FACES SEVERAL CHALLENGES TO COVID-19 MANAGEMENT INCLUDING LOW VACCINE RATES, OVER-EXTENDED COMMUNITY HEALTH PARTNERS STRUGGLING TO MANAGE BOTH COVID-19 TESTING AND VACCINATION, DECREASING COVID-19 TESTING NUMBERS, AND LARGE POPULATIONS AT ELEVATED RISK, INCLUDING THOSE WITH OR AT RISK FOR DIABETES, INDIVIDUALS AT LOWER SOCIOECONOMIC LEVELS, AND AFRICAN AMERICAN/BLACK AND LATINX COMMUNITIES. IN PROJECT PEACH2, WE PROPOSE TO LEVERAGE THE COMMUNITY PARTNERSHIPS DEVELOPED AND EXPANDED AT PART OF PROJECT PEACH TO GATHER ADDITIONAL INFORMATION ON COVID-19 TESTING, WITH A PARTICULAR FOCUS ON AT-HOME TESTING SOLUTIONS (AIM 1), USING BOTH QUANTITATIVE (AN EXPANSION OF THE FOLLOW-UP SURVEYS ALREADY BEING CONDUCTED AS PART OF PROJECT PEACH) AND QUALITATIVE (IN-DEPTH INTERVIEWS WITH 100 COMMUNITY MEMBERS, KEY STAKEHOLDERS, AND COMMUNITY PARTNERS) METHODS. THIS DATA, ALONG WITH THE FINDINGS OF PROJECT PEACH AND GEORGIA CEAL (1OT2HL156812-01/16-312-0217571-66105L), WILL BE USED TO DEVELOP TEXT MESSAGE, BEHAVIORAL NUDGES TO PROMOTE CONTINUED COVID-19 TESTING, REPORTING AND PREVENTIVE BEHAVIORS INCLUDING VACCINATION TARGETED TO PARTICIPANTS’ RACE/ETHNICITY, SEX, AGE, VACCINATION STATUS, AND TESTING HISTORY. WE WILL THEN EVALUATE (AIM 2A) THE UPTAKE, USAGE, AND VIEWS OF A HOME TESTING PLATFORM (PROVISION A SINGLE HOME COVID-19 TEST KIT FOR EACH HOUSEHOLD FAMILY MEMBER, COLLECTION OF TEST RESULTS VIA AN ONLINE REPORTING SYSTEM, AND TARGETED BEHAVIORAL NUDGES DELIVERED VIA TEXT MESSAGES) IN A RANDOMIZED COMMUNITY- BASED, ADAPTIVE INTERVENTION TRIAL (N=600) TARGETING INDIVIDUALS AFFECTED BY DIABETES THROUGH COLLABORATIONS WITH COMMUNITY PARTNER SITES (FAITH- AND COMMUNITY-BASED ORGANIZATION, THE GRADY DIABETES CLINIC, COVID-19 COMMUNITY TESTING AND VACCINE DISTRIBUTION SITES). WE WILL ALSO ASSESS (AIM 2B) HOW THE HOME TESTING PLATFORM AFFECTS VACCINE UPTAKE AND HESITANCY AMONG STUDY PARTICIPANTS AND FAMILY MEMBERS. THIS STUDY WILL BUILD ON THE SUCCESSFUL COMMUNITY-ACADEMIC PARTNERSHIPS CREATED THROUGH PROJECT PEACH TO FURTHER PROMOTE COVID- 19 TESTING AMONG THE MOST VULNERABLE COMMUNITIES IN GEORGIA. LESSONS LEARNED CAN BE DISSEMINATED TO OTHER AT-RISK COMMUNITIES AND CAN BE ADAPTED TO PROMOTE HOME-BASED TESTING FOR OTHER CONDITIONS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"FLORIDA INTERNATIONAL UNIVERSITY","value":996839.06,"savings":137496,"link":null,"description":"ABSTRACT Liver disease is a major cause of death in HIV infected persons in the United States. While advances in antiretroviral therapy have significantly reduced HIV-related mortality, co-infection with hepatitis C virus (HCV), is widespread and accelerates progression of liver fibrosis to cirrhosis and liver carcinoma. In addition, substance abuse accelerates HIV disease, and may facilitate progression of liver fibrosis. The primary goal of this proposal is to continue to follow the existing Miami Adult Studies on HIV (MASH) cohort, its specimen repository and database, and expand it from the current 881 to 1,500 study participants. The purpose is to generate collaborative studies to investigate the impact of cocaine, by far the most prevalent drug of abuse in South Florida, on HIV infection, HIV/HCV co-infection, and on long-term morbidity with a focus on liver disease in this population with disparities in access to care. HIV and HCV un-infected cocaine users and non-users will also be recruited to allow determination of the impact of cocaine use alone, as well as the interaction of cocaine use with HIV, HCV, and HIV/HCV co-infection. As new and more effective treatments and access to care for HIV, HCV and drug abuse become available, maintaining a well- characterized cohort, specimen repository and database will create a strong resource platform for current and future collaborative research. Observing the uptake of new HCV treatments and potential new cocaine cessation programs in this at-risk population with health disparities will provide data on barriers and facilitators to effective treatments to prevent long-term morbidity and mortality. We have followed the MASH cohort of 881 participants for up to 12 years with excellent retention rates, and have created a specimen repository and a database. The MASH cohort in Miami is unique because it will be a mostly Hispanic cohort with a large number of African Americans, women, non-injector drug users, with predominantly heterosexual HIV- transmission etiology. We propose to (1) compare the progression of liver fibrosis over four years among cocaine users and non-users in HIV+/HCV-, HIV+/HCV+, HIV-/HCV+, and HIV-/HCV-, using a novel non- invasive diagnostic device, the Magnetic Resonance Elastography (MRE). We also propose to (2) compare the pattern over four years of biomarkers and identify genetic markers associated with the mechanisms of liver fibrosis among cocaine users and non-users. Understanding the role of cocaine use in the context of HIV and HIV/HCV co-infections and lack of lasting effects of treatments for cocaine use cessation are crucial in order to gain insights into the pathogenesis and disease outcomes, and to provide the basis for identifying antifibrotic therapies such as oxidative stress, which are amenable to intervention. These studies will be critical for program development, appropriate interventions, and for improving health in this population."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"GENENDEAVOR LLC","value":4504502,"savings":753881,"link":null,"description":"DEVELOPMENT OF A HANDHELD RAPID AIR SENSING SYSTEM TO MONITOR AND QUANTIFY SARS-COV-2 IN AEROSOLS IN REAL-TIME - PROJECT SUMMARY THE ABILITY TO RAPIDLY MONITOR SARS-COV-2 IN AEROSOL—DROP PARTICLES <5 ÎœM IN SIZE THAT EVAPORATE INTO DROPLET NUCLEI AND BECOME SUSPENDED IN AIR—AT THE POINT OF PRESENTATION IS CRITICAL TO MANAGING THE RISK OF INFECTION BY AIRBORNE TRANSMISSION AS PEOPLE RETURN TO THEIR COMMUNITIES, WORKPLACES, AND SCHOOLS DURING THE COVID-19 PANDEMIC. HOWEVER, CURRENT ENZYME-BASED METHODS LACK SENSITIVITY, SPEED, SIMPLICITY, AND REQUIRE LAB EQUIPMENT—HENCE, LACK THE CAPABILITY FOR REAL-TIME POINT-OF-PRESENTATION (POP) MONITORING. IN THE ABSENCE OF A REAL-TIME POP MONITORING CAPABILITY, SARS-COV-2 TRANSMISSION REMAINS POORLY UNDERSTOOD. IN THIS APPLICATION, A MULTIDISCIPLINARY RESEARCH APPROACH THAT INTEGRATES INNOVATIONS IN RAPID-KINETIC CHEMICAL AUTO-LIGATION, NON- ENZYMATIC ISOTHERMAL SIGNAL AMPLIFICATION, SOLID-STATE ELECTRONICS, AND BIOPHOTONICS IS PROPOSED TO ENABLE THE DEVELOPMENT OF A NOVEL AIR MONITORING SYSTEM (AMS) THAT DETECTS AND QUANTIFIES AEROSOLIZED SARS-COV-2 AT THE POINT OF PRESENTATION IN REAL-TIME. RECENT ADVANCES IN VIRAL CULTURING PROTOCOLS, AIR SAMPLING TECHNOLOGY, AND SINGLE-PHOTON DETECTION CAPABILITY WILL PROVIDE THE FRAMEWORK FOR A COLLABORATIVE RESEARCH ENDEAVOR TO ESTABLISH A NEW PARADIGM TO ADDRESS THE KNOWLEDGE GAP BETWEEN THE SPREAD OF COVID-19 AND SARS-COV-2 AEROSOL TRANSMISSION. THEREFORE, THE PROPOSAL IS AIMED AT TRANSFORMING THE WAY COVID-19 IS CURRENTLY RESEARCHED BY PROVIDING A TOOL TO ENABLE UNPARALLELED STUDIES THAT WILL SIGNIFICANTLY ADVANCE THE CURRENT KNOWLEDGEBASE. THESE TRANSFORMATIVE STUDIES COULD ULTIMATELY GUIDE A NEW FIELD OF INVESTIGATIONS THAT LEAD TO A BETTER UNDERSTANDING OF COVID-19 SPREAD, SUCH AS VIRAL EXPOSURE VS. RISK, VIRAL DECAY RATE VS. INFECTIVITY, AND VIRAL LOAD VS. INFECTIOUS DOSE IN SARS-COV-2 AIRBORNE TRANSMISSION. AT A MINIMUM, THE PROPOSED THREE RESEARCH OBJECTIVES WILL PROVIDE A BASIC UNDERSTANDING OF COVID-19 AEROSOL TRANSMISSION. FIRSTLY, CURRENT AIR SAMPLING SYSTEMS USE A MULTI-STEP WORKFLOW THAT TAKES SEVERAL HOURS TO COMPLETE AND REQUIRES LAB EQUIPMENT, REAGENTS, AND SIGNIFICANT HANDS-ON TIME. THE GOAL OF OBJECTIVE 1 IS TO COMBINE AIR SAMPLING AND DETECTION INTO A ONE-STEP REAL-TIME POP AMS DEVICE THAT YIELDS SARS-COV-2 QUANTIFICATION RESULTS IN LESS THAN 5 MINUTES, WITHOUT LAB EQUIPMENT OR REAGENTS. SECONDLY, VIRAL INOCULUM, OR INITIAL DOSE OF VIRUS, ASPIRATED INTO THE NASAL CAVITY AND LUNGS HAS BEEN ASSOCIATED WITH DISEASE ONSET AND SEVERITY. THE GOAL OF OBJECTIVE 2 IS TO OPTIMIZE AND VALIDATE AMS TO CORRELATE READINGS FROM THE AIR MONITORING DEVICE WITH TISSUE-CULTURE INFECTIOUS DOSE (TCID50) AND REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION (RT-PCR) QUANTITIES. THESE PARAMETERS CAN THEN LATER BE APPLIED TO HUMAN STUDIES TO DETERMINE THE HUMAN INFECTIOUS DOSE OF SARS-COV-2 BY AEROSOL TRANSMISSION. THIRDLY, FIELD-BASED TESTING IN HOSPITALS WILL PROVIDE A MEANS TO BETA TEST AMS PERFORMANCE IN HIGH-RISK ENVIRONMENTS. THE GOAL OF OBJECTIVE 3 IS TO CALIBRATE AMS MEASUREMENTS WITH RT-PCR CYCLE-THRESHOLD (CT) VALUES AND CELL-CULTURE TCID50 VIABILITY RESULTS AND THEN BENCHMARK WITH RESULTS FROM HIGH-RISK ENVIRONMENTS TAKEN FROM AROUND THE WORLD TO CORRELATE SARS-COV-2 AEROSOL CONCENTRATIONS WITH GLOBAL INFECTION RATE, AS A POTENTIAL FOR ESTABLISHING THRESHOLD LEVELS."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"HARVARD UNIVERSITY, SCHOOL OF PUBLIC HEALTH","value":1844641.46,"savings":750604,"link":null,"description":"We will develop methods to enhance the design and analysis of serologic studies of populations with respect to COVID-19, including methods that may be generalized in the future to address challenges raised by other seasonal diseases (such as influenza) and newly emerging diseases. In addition, we will use serologic data in innovative ways to underpin mathematical models that can project population-level trends. Early serosurveys using convenience samples of the population and serologic assays with variable and often uncertain sensitivity and specificity were heavily criticized, for unrepresentativeness and inadequate accounting for test characteristics, resulting in bias and overconfidence (unduly narrow confidence bounds). Aim 1 will develop methods for valid inference of seroprevalence, specifically by (a) accounting for biased sampling, (b) accounting for imperfect tests, and (c) developing and testing a novel approach to snowball sampling employing serologic tests to enhance outbreak detection and contact tracing. Valid comparisons that assess seroprotection—whether, how much, and how long an individual is protected by an immune response to a COVID-19 infection (specifically, by antibodies) against reinfection—rely on adequate control for confounding, an issue that arises in multiple ways specific to seroprotection studies. Likewise, waning of seroprotection may be inferred in error if studies are not carefully designed and analyzed. The unprecedented efforts to develop detailed serologic and systems serologic data sets provide new forms of data that can be leveraged to better inform these inferences. Aim 2 will develop a suite of methods to enhance causal inference in seroprotection studies, including (a) sample size and power calculations; and (b) improved exploitation of serological data to reduce biases due to confounding and risk compensation. Aim 3 will develop new mathematical modeling approaches and apply them to quantify the likely reduction in the herd immunity threshold for COVID-19 due to various forms of risk heterogeneity and assortativeness in mixing. Aim 4 will develop models of COVID-19 transmission that accommodate emerging evidence about the duration and nature of immunity to infection, shedding, and symptoms, to obtain estimates of how illness attack rates will differ under varying assumptions about the progress of immunity. Aim 5 will develop transmission models to assess optimal cohorting arrangements in congregate facilities (eg prisons and nursing homes), with special attention to the nature of immunity required for these arrangements to be beneficial. Finally, vaccine supplies may be initially limited, necessitating efficient use of them. Aim 6 will investigate the use of serologic data in combination with other types of data to optimize allocation of scarce vaccines."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"HEALTH RESEARCH, INC.","value":840583.29,"savings":457954,"link":null,"description":"Project Summary As the COVID-19 pandemic continues to spread across the United States it is imperative that we implement technologies to screen large swaths of the population for the presence of antibodies to SARS-CoV-2. Serological surveillance not only affords a measure of virus exposure within a community at large but also provides information necessary to predict outbreak dynamics. Furthermore, as our understanding of how humoral factors contribute to controlling (and possibly exacerbating) COVID-19, it will be essential to have methods in place to measure the “quantity” and “quality” of antibodies associated with both natural SARS-CoV- 2 exposure and candidate SARS-CoV-2 vaccines. This U01 proposal seeks to advance the use of dried blood spots (DBS) in conjunction with a Luminex-based microsphere immunoassay (MIA) to enable high-throughput (HT) population-wide serological surveillance for SARS-CoV-2. Specifically, the proposal will expand the HT- DBS assay to capture the breadth and complexity of SARS-CoV-2 antibody responses following natural infection, and develop a high-throughput competitive immunoassay (CIA) as a surrogate measure of SARS- CoV-2 neutralizing antibody titers in DBS. The proposed platform technologies to be developed at the Wadsworth Center will contribute directly to NCI’s mission to “… develop, validate, improve and implement serological testing and associated technologies…” to address the COVID-19 pandemic."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI","value":3649452.31,"savings":979989,"link":null,"description":"OVERALL ABSTRACT The overarching research theme for the Mount Sinai U54 Serological Center of Excellence “Vulnerability of SARS-CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses,” is to fill the vital knowledge gap in factors contributing to the great vulnerability of lung cancer patients to morbidity and mortality from SARS- CoV-2 infection through serological analysis of antibody responses and studies of inter-individual variation in patient-derived lung tumor and epithelial cells to SARS-CoV-2 infection. We will characterize and compare lung cancer patients’ antibody responses to SARS-CoV-2 infection or SARS-CoV-2 vaccines with a matched non- lung cancer control group; quantitate differences in SARS-CoV-2 viral replication in lung cancer and normal lung epithelial cells from different lung cancer patients; and quantitate differences in neutralizing antibody responses in lung cancer patients. This information is urgently needed to enact vaccine and other strategies for protecting lung cancer patients against development of COVID-19. While antibodies, induced by infection or vaccines, are protective against many viruses, it has not yet been established if antibodies to SARS-CoV-2 are protective, how much and what types of antibody are needed for protection, and how long protection will last are unknown. Likewise, we do not know if lung cancer patients can mount an effective immune response and if different aspects of lung cancer or its treatment influences this immune response. Our overall hypothesis is that lung cancer patients have a different (e. g. weaker) antibody response to SARS-CoV-2 infection compared to persons without lung cancer, and that their lung cancer or lung epithelial cells play a role in viral replication of host responses, which together could explain the aggressive course and high fatality rate demonstrated in lung cancer patients with COVID-19. Our U54 will determine whether natural infection or SARS-CoV-2 vaccines (forecast for deployment) will give comparable serological antibody responses longitudinally in 1,000 lung cancer patients and a matched non-lung cancer control group (1,000 individuals); and determine if there are differences in antibody responses related to age, gender, tobacco history, and race/ethnicity. The U54 proposal has two Projects and three Cores (Administrative, Clinical, and Data Sciences). Project 1: “Characterization of the Antibody Response to SARS-CoV-2 in Lung Cancer Patients” quantitatively characterizes anti-SARs-CoV-2 antibody responses and their functionality longitudinally in lung cancer patients compared to a control population after natural infection and vaccination, and relates the serological response characteristics to key clinical, demographic information. Project 2: “Susceptibility of Lung Cancer Cells to SARS-CoV-2 Infection and Antibody- Mediated Neutralization,” determines the inter-individual variation in lung cancers and lung epithelial cells to support SARS-CoV-2 viral replication, the inter-individual variation of antibodies to neutralize viral infection, and how these host viral responses relate to host cell characteristics and important clinical demographic information."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"JOHNS HOPKINS UNIVERSITY","value":2444726,"savings":529448,"link":null,"description":"The COVID-19 pandemic disproportionately impacts Latinos in the US. COVID-19 testing remains critical for tracking and slowing the spread of the virus and preventing future outbreaks, particularly in communities disproportionately affected by COVID-19 and where vaccination coverage is suboptimal. The goal of this project is to expand our RADx-UP Phase 1 COVID-19 testing project Vive Sin Duda to implement and evaluate innovative implementation strategies to increase reach, access, and uptake of COVID-19 homebased self-testing (HST) among low-income Latinos in Maryland. We will implement and evaluate two COVID19 HST distribution approaches: 1) Network-based; and 2) Social marketing. We will also incorporate data driven iterative changes to optimize a community health worker (CHW)-led short message service (SMS) platform to support HST and linkage to COVID-19 care, vaccination, and other services (e.g., cash and food assistance). Primary and secondary outcomes include: 1) Reach and uptake of HST; and 2) Linkage to care for those who test positive or vaccination for unvaccinated people who test negative. Leveraging our existing community coalition, testing and vaccination clinics, and a team of bilingual and bicultural CHWs, we are well poised to implement a COVID-19 HST program and measure its impact. Our research will provide important new information that will improve access and uptake of innovative COVID-19 testing technology. It also will fill critical knowledge gaps to guide the translation of evidence-based interventions into widespread adoption by RADx-UP consortium members."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"JOHNS HOPKINS UNIVERSITY","value":3415637.4,"savings":207262,"link":null,"description":"JOHNS HOPKINS EXCELLENCE IN PATHOGENESIS AND IMMUNITY CENTER FOR SARS-COV-2 (JH-EPICS)"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"JOHNS HOPKINS UNIVERSITY","value":1228745,"savings":196005,"link":null,"description":"EXOSOME-BASED NON-TRADITIONAL TECHNOLOGIES TOWARDS MULTI-PARAMETRIC AND INTEGRATED APPROACHES FOR SARS-COV-2"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"KAISER FOUNDATION RESEARCH INSTITUTE","value":1014171,"savings":628149,"link":null,"description":"SARS-COV-2 SEROLOGICAL ANTIBODY TESTING FOR DISEASE SURVEILLANCE AND CLINICAL USE"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"KECK GRADUATE INSTITUTE OF APPLIED LIFE SCIENCES","value":3071572,"savings":374778,"link":null,"description":"RAPID RESPONSE FOR PANDEMICS: SINGLE CELL SEQUENCING AND DEEP LEARNING TO PREDICT ANTIBODY SEQUENCES AGAINST AN EMERGING ANTIGEN - ABSTRACT ONE OF THE “HOLY GRAILS” IN IMMUNOLOGY IS TO BE ABLE TO DIRECTLY PREDICT TIGHT-BINDING VARIABLE CHAIN ANTIBODY SEQUENCES IN SILICO AGAINST FOREIGN OR NON-SELF `ANTIGENIC' PROTEINS. IMMUNOGLOBULIN CHAIN REARRANGEMENT CAN POTENTIALLY ENCODE APPROXIMATELY 1016 DIFFERENT VARIANTS OF ANTIBODY HEAVY AND LIGHT CHAIN SEQUENCES. HOWEVER, ONLY A SMALL FRACTION OF THE SEQUENCE SPACE IS GENERALLY ACCESSED FOR EVOLVING ANTIBODIES AGAINST FOREIGN PROTEINS. THE COMPUTATIONAL CHALLENGE IS TO GO FROM A MODEL OF THE STRUCTURE OF AN ANTIGEN TO PREDICTING A SET OF ANTIBODY CHAIN SEQUENCES THAT CAN BIND TIGHTLY TO THE ANTIGEN. IF SOLVED, IT MIGHT BE POSSIBLE TO MOVE IN LESS THAN 24 HOURS FROM THE FIRST CRYO-ELECTRON-MICROSCOPIC STRUCTURE OF A NOVEL VIRAL PROTEIN TO ADVANCE A SET OF POTENT ANTIBODY-LIKE MOLECULAR CANDIDATES FOR TESTING. TOWARDS SOLVING THIS PROBLEM, THIS PROJECT AIMS TO DEVELOP A DEEP LEARNING ARCHITECTURE THAT WILL TAKE AS INPUT THERMODYNAMIC, QUANTUM MECHANICAL (DENSITY FUNCTIONAL), AND LOCAL STRUCTURE- BASED NETWORK TOPOGRAPHICAL FEATURES OF THE ANTIGENS AND THEIR COGNATE ANTIBODIES, AND WILL OUTPUT THEIR RESPECTIVE BINDING AFFINITY CONSTANTS. WE WILL DESIGN A GENERATIVE ADVERSARIAL NETWORK (GAN), WHICH WE THINK IS UNIQUELY SUITED FOR REGRESSION-BASED ML APPROACHES FOR THE IMMUNE SYSTEM, TO DISCOVER ASSOCIATIONS BETWEEN THE EPITOPE AND THE VARIABLE CHAIN FEATURES. THIS APPROACH REQUIRES A LARGE DATA STREAM OF ANTIGEN AND COGNATE ANTIBODY SEQUENCES, WHICH UNTIL RECENTLY WAS DIFFICULT TO OBTAIN. A RECENTLY DESCRIBED SINGLE B-CELL RECEPTOR (BCR) SPECIFIC TAGGING METHOD COUPLED WITH SINGLE CELL DEEP SEQUENCING (“LINKING B CELL RECEPTOR TO ANTIGEN SPECIFICITY THROUGH SEQUENCING” OR LIBRA- SEQ) CAN RAPIDLY ISOLATE AND SEQUENCE THE BCR VARIABLE CHAIN CODING REGIONS THAT CAN BIND WITH HIGH SELECTIVITY TO ANTIGENIC EPITOPES. TOWARDS THE SPECIFIC PROJECT GOALS, IN TASK 1, LIBRA-SEQ WILL BE USED TO RAPIDLY IDENTIFY AND GENERATE CANDIDATE IMMUNOGLOBULIN CODING SEQUENCES IN RESPONSE TO SPECIFIC LINEAR AND NONLINEAR EPITOPES (AGAINST CONTROLS), CHOSEN THROUGH COMPUTATIONAL/MOLECULAR MODELING AND PRIORITIZED WITH SARS-COV-2 SPIKE PROTEIN EPITOPES (BUT NOT RESTRICTED TO THESE), INJECTED INTO A MOUSE MODEL, TO GENERATE LARGE TRAINING SETS; IN TASK 2, THESE TRAINING SETS, ALONG WITH OTHER DATA SETS ALREADY AVAILABLE IN PUBLIC DATABASES, WILL GENERATE A SERIES OF STRUCTURAL FEATURES (DESCRIBED ABOVE), WHICH WILL BE USED TO TRAIN THE GAN; IN TASK 3, THE PREDICTED EPITOPE-ANTIBODY INTERACTIONS WILL BE VALIDATED BY DIRECT EXPERIMENTS WITH SYNTHETIC ANTIBODY AND PHAGE-DISPLAY SYSTEMS. THUS, THE PROPOSED STRATEGY COMBINES FOUNDATIONAL PRINCIPLES IN EVOLUTIONARY BIOLOGY, GENOMICS, STRUCTURAL CHEMISTRY, AND COMPUTER SCIENCE TO THE SOLUTION OF A GENERAL BIOLOGICAL ENGINEERING PROBLEM. RESULTS FROM THIS PROJECT ARE EXPECTED TO LAY THE FOUNDATIONS FOR A RIGOROUSLY TESTED AND FULLY AUTOMATED MACHINE- LEARNING SYSTEM THAT COULD RAPIDLY GENERATE SYNTHETIC ANTIBODY CANDIDATES FROM THE STRUCTURE OF A NOVEL VIRUS PROTEIN, WHICH CAN ENHANCE THE RAPID RESPONSE ABILITY AGAINST A FUTURE PANDEMIC. THE ABILITY TO DEVELOP TARGETED ANTIBODY THERAPY AGAINST NON-INFECTIOUS OR CHRONIC DISEASES, AND ON THE PRODUCTION OF ANTIBODY-BASED INDUSTRIAL ENZYMES, WILL ALSO BE DRAMATICALLY ENHANCED IF THIS PROJECT WERE TO BE SUCCESSFUL. THE TEAM: THE TEAM-LEADS OF THIS MULTI-INSTITUTIONAL RESEARCH PROJECT COMPRISE A COMPUTER SCIENTIST, A PROTEIN CRYSTALLOGRAPHER, AN IMMUNOLOGIST, AND A MOLECULAR BIOLOGIST. 1"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"La Jolla Institute For Immunology","value":1130292,"savings":139332,"link":null,"description":"PROJECT SUMMARY This multi-PI proposal titled “SARS-CoV-2-reactive subjects” is written in response to ‘RFA-CA-20-039’ - tissue-resident memory T cells in healthy and cancer Research projects in SARS-CoV-2 Serological Sciences. Recent studies have shown that antibody responses to SARS-CoV-2 infection decline rapidly over time, implying a lack of durable protective humoral (B cell) immunity. Whether this is also true for cellular immunity (e.g., T cells) is poorly understood. It is well established that CD8+ TRM cells are the first line of defense in viral infections at mucosal/barrier sites. They are also known to protect hosts against homologous or heterologous re-infections. Our group was the first to show that TRM cells are pivotal players in driving effective anti-tumor immune responses in lung cancer, and that TRM cells are the primary cellular targets of anti-PD1 therapies. These key findings were possible because of the ongoing collaboration between Dr. Vijayanand, Dr. Ay, and Dr. Ottensmeier (Multi-PI). This team brings together experience in T cell immunology, single-cell genomics, bioinformatics, and cancer immunology. Our Multi-PI team has recently performed the first and largest single-cell RNA-seq and TCR-seq analysis of SARS-CoV-2-reactive CD8+ and CD4+ T cells (~300,000 single-cells) from COVID-19 patients. Here, to understand TRM responses to SARS-CoV-2, we will capitalize on a cohort of cancer (n=100) and non-cancer (n=100) patients, who will provide excess airway (nasal, oropharynx, larynx), lung and tumor tissue specimens obtained during routine surgery. In AIM 1, we will define the properties of SARS-CoV-2 reactive TRM cells from cancer and non-cancer patients with or without previous SARS-CoV-2 infection. We will perform combined single-cell RNA-seq and TCR-seq analysis of CD8+ TRM cells in the airways (nasal, oropharynx), lung, and tumor tissue. In parallel, by stimulating PBMCs with SARS-CoV-2 peptide pool, we will determine the transcriptomic and TCR sequence of SARS-CoV-2 reactive T cells. We will utilize this TCR sequence information to define the numbers and properties of SARS-CoV-2 reactive-TRM cells in mucosal and tumor tissues. Recent studies in non- exposed individuals (pre-COVID-19 pandemic) indicate pre-existing, circulating CD8+ T cells, with human coronavirus cross-reactivity. Here, we will measure the quantity and quality of pre-existing SARS-CoV-2 cross- reactive TRM responses in subjects without clinical or serological evidence of previous SARS-CoV-2 infection. In AIM 2, we will assess the impact of SARS-CoV-2 infection on anti-tumor and other anti-viral TRM responses. We will stimulate matched PBMCs (as above) with peptide pools targeting (i) common respiratory RNA viruses (influenza (FLU), RSV), (ii) persistent DNA viruses (CMV, EBV), and (iii) a tumor-driving virus (HPV) to define the TCR sequence of the respective virus-specific and tumor(HPV)-specific CD8+ T cells; we will utilize the TCR information to determine frequency and properties of other virus/tumor-reactive TRM cells in mucosal and tumor- tissue cells."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"Massachusetts General Hospital, The","value":14086805,"savings":621853,"link":null,"description":"Project Summary/Abstract: Overall The Point-of-Care Technology Research Center in Primary Care proposes to further develop a national “center-without-walls” for rapid transformation of emerging point-of-care technologies into commercially viable, clinically focused solutions for improving primary healthcare. The Center was established by the Consortia for Improving Medicine through Innovation and Technology (CIMIT), a consortium of research institutions, universities, military medicine centers and hospitals throughout the US with international affiliates at University of Manchester-UK (MIMIT), Barcelona (The Center for the Integration of Medicine and Innovative Technologies in Catalonia) and Singapore (A*-STAR/Eastern Health Alliance). CIMIT established the Point-of- Care Technology Research Center in Primary Care under a Cooperative Agreement (U54) award from National Institute of Biomedical Imaging and Bioengineering (NIBIB) in 2012 and the Center created a national network of research sites, harnessing the power of multidisciplinary collaboration to speed the translation of high-impact research into primary care practice and broader dissemination by commercially licensable opportunities. We will build upon our proven approach to needs-driven primary healthcare technology innovation to expand and significantly enhance our Center. The Center’s overall objective is to build upon the progress made under the previous U54 award and offer expanded support to teams through the integrated functional elements of the proposed enhanced Center. In so doing, the Center will offer a portfolio of synergistic support to teams with innovative solutions through defined interfaces and hand offs throughout the innovation process while continuously improving the Center’s processes of finding, funding, facilitating, and following projects. The long-term goal is to create a dynamic, sustainable national network that identifies key unmet needs in the delivery of primary care as well as promising emerging technologies and then to accelerate their translation into clinical applications for broad impact in primary care medicine through high-quality translational and clinical research."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"MICHIGAN STATE UNIVERSITY","value":964759,"savings":270744,"link":null,"description":"CULTURALLY-TARGETED COMMUNICATION TO PROMOTE SARS-COV-2 ANTIBODY TESTING IN SALIVA:  ENABLING EVALUATION OF INFLAMMATORY PATHWAYS IN COVID-19 RACIAL DISPARITIES"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"NEW YORK UNIVERSITY MEDICAL CENTER","value":33203136,"savings":13966992,"link":null,"description":"OTA-21-015A Post-Acute Sequelae of SARS-CoV-2 Infection Initiative: NYU Langone Health Clinical Science Core, Data Resource Core, and PASC Biorepository Core"},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"OHIO STATE UNIVERSITY","value":3143795,"savings":734515,"link":null,"description":"Overall Project Summary Stemming the spread of COVID-19 will require research that cross-cuts basic, translational, and applied sciences. The Center for Serological Testing to Improve Outcomes from Pandemic COVID-19 (STOP- COVID) is proposed as a transdisciplinary entity to understand the interface between exposure risk, transmission, immune responses, disease severity, protection, and barriers to testing/vaccination, with the goal of improving population health and clinical outcomes. The Center will utilize state-of-the-art serological and molecular tests, developed at OSU, in a longitudinal study of first responders, a group at continual high risk of SARS-CoV-2 exposure, as well as their household contacts. Through the proposed work, STOP-COVID investigators will understand critical aspects of: (i) transmission in both asymptomatic and symptomatic individuals, (ii) immune, host, and viral determinants of disease outcome, and (iii) factors associated with immune protection. Center investigators will also identify best practices for communication of test results and information about COVID-19 to improve understanding of risk, transmission, and protection, while reducing access barriers to testing. The Center to STOP-COVID will: Aim 1 Develop Institute Infrastructure through three shared resource cores: 1. An Administrative Core that provides overall direction and leadership, coordinating all Center activities as well as Project–Core–SeroNet interactions; 2. A Testing and Biorepository Core, whose role is to perform first-tier serologic and viral testing during our longitudinal study using high throughput ELISA and neutralization assays developed at OSU, and cost-shared by OSU; and 3. A Data Management and Analysis Core that will provide project investigators with a centralized resource for biostatistics, bioinformatics, epidemiology, and psychometrics expertise. Aim 2: Conduct three innovative research projects to address: Project 1: Parallel serological and viral testing to determine COVID-19 prevalence, transmission, and protection in extended first responder cohorts. This project will also generate serology data for vaccines or mAbs, once available to this presumably high-priority group; Project 2: Serologic and molecular determinants of COVID-19 severity and immune protection. This project will evaluate COVID-19 serological responses in the context of SARS-CoV-2 and common cold CoV (CCCoV) antibodies, using novel assays specific for a panel of antigens. Project 2 also will employ transcriptomics to understand how host genetics, CCCoV, other respiratory viruses, and immune responses contribute to pathogenesis; and Project 3: Responding to changing serological and viral information around COVID-19. This project will incorporate results from Projects 1 & 2 and SeroNet to inform best practices in risk communication, provide behavioral guidance to decrease transmission, and enhance protection from disease. Aim 3: SeroNet Participation and Sharing of Data and Best Practices. We will leverage STOP-COVID infrastructure to share data, results, reagents, and best practices with SeroNet, which will drive new discoveries and their translation into actionable strategies for implementation across all groups affected by COVID-19."},{"date":"3/23/2025","agency":"Department of Health and Human Services","recipient":"OREGON HEALTH & SCIENCE UNIVERSITY","value":1286550,"savings":264685,"link":null,"description":"EFFECT OF OBESITY ON HIV PATHOGENESIS, ANTIRETROVIRAL THERAPY, AND METABOLIC COMORBIDITIES"}]},"meta":{"total_results":15887,"pages":159}}