P01AI177687

Multi-omics analysis of broadly neutralizing antibodies and therapeutic vaccination - Summary

The goal of this P01 program is to define mechanisms of efficacy of broadly neutralizing antibodies (BNABs) and therapeutic vaccines for HIV-1 in a highly collaborative and multifaceted research program. Our overall hypothesis is that immunologic strategies for HIV-1 cure delay viral rebound both by targeting the viral reservoir and by increasing host antiviral immunity.

We will evaluate mechanisms of therapeutic efficacy in both humans and nonhuman primates (NHPS) using coordinated virologic, immunologic, and multi-omic approaches with the goal of developing improved next generation HIV-1 cure strategies. We will apply cutting-edge, high-throughput, multi-omic profiling platforms and integrate these data sets to generate a comprehensive tissue landscape and regulatory network of the viral reservoir and host immune responses.

This program builds on our existing studies over the past several years in both humans and NHPS evaluating the ability of BNABs and therapeutic vaccines to delay viral rebound following discontinuation of antiretroviral therapy (ART). We will first utilize existing samples from these studies to generate hypotheses regarding correlates of delayed viral rebound. We will then perform new interventional studies in NHPS with spatial multi-omic analyses in lymph nodes and gastrointestinal mucosal tissues to test hypotheses in order to define mechanisms of reservoir targeting by BNABs and therapeutic vaccines.

The significance of this program is the potential to define the biologic pathways that lead to delayed viral rebound following ART discontinuation. An improved understanding of partially effective BNABs and therapeutic vaccines in humans and NHPS will lead to basic research advances that will allow the development of improved next generation HIV-1 cure approaches.

To accomplish the goals of this P01 program, we propose the following projects and cores:

Project 1. Multi-omics correlates of broadly neutralizing antibody efficacy
Project 2. Multi-omics correlates of therapeutic vaccine efficacy
Core A. Administrative Core
Core B. Multi-omics Core
Core C. Computational Analysis Core
Core D. NHP Core

Beth Israel Deaconess Medical Center

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]

Boston, Massachusetts 022155400 United States

Single Zip Code

A Multi-omics Approach to Immune Responses in HIV Vaccination and Intervention (P01 Clinical Trial Not Allowed) (RFA-AI-22-038)

Amendment Since initial award the total obligations have increased 214% from $1,412,696 to $4,429,179.