UM1AI164565

Reach: Research Enterprise to Advance a Cure for HIV - Project Summary/Abstract

Despite the success of standard antiretroviral therapy (ART), the need for an HIV cure remains compelling, both to improve the lives of people living with HIV (PWH) and to bring about the end of the pandemic. Strategies for an HIV cure fall under two categories: those that seek ART-free 'remission', and those targeting a classical cure or 'eradication'. While precedents exist for both scenarios, the latter have only been achieved with bone marrow transplantation.

In contrast, although naturally occurring immune-mediated control of HIV (remission) is relatively rare, many such cases have been described. Our proposed "Martin Delaney Collaboratory for HIV Cure Research" program is entitled "Reach" - Research Enterprise to Advance a Cure for HIV. The central theme of Reach is that cellular immune responses (NK and T-cells), combined with next-generation virus-neutralizing biologics, can be harnessed to achieve durable remission and eradication of HIV reservoirs.

The proposed research focuses on closing gaps in our understanding of the fundamentals of the system that we are trying to perturb, i.e.: the HIV reservoir in relation to cellular immunity, as the means to achieve real progress towards effective and viable HIV cure strategies. Our approach centers around three research foci, which emphasize back to basics science, but connect this with discovery to translational pipelines directed towards both remission and eradication.

The proposed objectives, broadly defined, aim to:
(1) Redefine the three-way relationship between the persistent HIV reservoir, CD8+ T-cells, and rebound virus at the levels of: single cells, individuals, and diverse populations.
(2) Harness conventional and unconventional (BNAB-induced) CD8+ T-cell responses, in combination with BNABs and 'next generation' biologics, to achieve durable control of HIV replication.
(3) Develop a discovery-to-translational pipeline to overcome multiple barriers to the eradication of HIV reservoirs by CTL/NK cells.

These studies will be rooted in a strong basic science program that will contextualize results with novel insights into barriers to immune-mediated reservoir elimination, including the role of the proviral integration site and of viral and host factors influencing immune susceptibility. Our program prioritizes the study of diverse populations, including African populations infected with non-B subtype virus, and women - both to advance towards a cure for all, and to benefit from diverse perspectives as a source of fundamental insights.

These objectives will be realized by a group of accomplished investigators of diverse expertise and with strong collaborative histories, along with community and industry partners.

Weill Medical College Of Cornell 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]

New York, New York 100654805 United States

Single Zip Code

Martin Delaney Collaboratories for HIV Cure Research (UM1 Clinical Trial Not Allowed) (RFA-AI-20-035)

Amendment Since initial award the total obligations have increased 21926% from $125,000 to $27,533,114.