UM1AI164566

Pediatric Adolescent Virus Elimination (PAVE) Martin Delaney Collaboratory - Abstract

The immediate establishment of the latent HIV-1 reservoir in resting memory CD4+ T cells precludes HIV-1 cure, compelling ART for a lifetime in children. The mission of the PAVE Collaboratory is to use cutting-edge science to establish a deep and broad understanding of the immunopathogenesis of pediatric HIV-1 reservoirs, across the age spectrum, and to demonstrate preclinical safety and efficacy of novel therapeutics to eradicate reservoirs and control rebound that will pave the way for future interventional human studies toward a lifetime of sustained HIV-1 control off ART.

We hypothesize that the unique features of the infant immune system at the time of reservoir establishment impact the characteristics of long-term virus persistence, susceptibility to immune-mediated clearance, and reactivation that are distinct from adult infections, warranting in-depth investigation to inform cure therapeutics suitable for children. We will test this hypothesis and execute the PAVE scientific agenda through accomplishment of the following specific aims:

1. Define the establishment and evolution of the HIV latent reservoir in perinatal infection.
2. Enhance pediatric immunity and broadly neutralizing antibody (BNAB) delivery to achieve post-treatment control of HIV-1 off ART.
3. Deploy immune-targeted strategies to eliminate virus reservoirs.
4. Optimize virologic, immunologic, and imaging methods to assess efficacy of HIV-1/S(H)IV cure interventions.
5. Foster community engagement in pediatric HIV cure research.

The PAVE program is multidisciplinary, multicultural, and iterative with a nimble structure encompassed by four highly synergistic research foci and a domestic and international community program that will rapidly incorporate new scientific directions and feedback from our stakeholders. The PAVE leadership team spans diverse scientific expertise and exhibits additional diversity in terms of gender, academic rank, and country of origin. Each of the research foci also includes junior faculty co-investigators to facilitate their career development within the HIV-1 research space.

Through the collective efforts of our scientific leadership, executive committee, scientific advisory board, investigators, industry partners, network collaborations, and domestic and international community program, PAVE anticipates meeting the following overall milestones:

1) Understanding early life immunity and early antiretroviral treatment on the composition and stability of the latent reservoir, including in naïve T cells, and potential for HIV-1 remission.
2) Eliminating these reservoirs in pre-clinical studies of immune-targeted strategies.
3) Defining the role of myeloid cells in HIV-1 persistence and rebound, including in the CNS.
4) Establishing novel approaches to enhance pediatric immunity through active and passive immunization.
5) Developing cutting-edge approaches to quantify and monitor proviral reservoirs to measure clinical trial efficacy.
6) Promoting active community engagement in pediatric HIV-1 cure research.

These milestones will help achieve the vision of sustained ART-free control of HIV-1 replication in pediatric populations.

The Johns Hopkins University

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS; TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Baltimore, Maryland 212051832 United States

Single Zip Code

Martin Delaney Collaboratory for Pediatric HIV Cure Research (UM1 Clinical Trial Not Allowed) (RFA-AI-20-036)

Amendment Since initial award the End Date has been extended from 04/30/26 to 04/30/27 and the total obligations have increased 1405% from $2,000,000 to $30,092,882.