UM1AI164556

I4C 2.0: Immunotherapy for Cure - Summary

The goals of I4C 2.0 are to advance our scientific understanding of the viral reservoir and to develop immunologic strategies for HIV-1 remission and eradication. This will be achieved through a highly collaborative and multifaceted research program involving partnerships among academia, industry, government, and the community. Our overall hypothesis is that multiple immunologic strategies will need to be explored and combined to achieve long-term, ART-free virologic control or complete virus eradication. The goal is to select combination regimens to advance into clinical development by the end of the proposed period of support.

We propose three research foci, a management and operations section, and a community engagement section.

Focus 1: Mechanistic Basis of Reservoir Targeting and Viral Persistence
Aim 1: To define a virologic, immunologic, and transcriptomic signature of viral persistence and rebound and to determine how immunologic strategies target the viral reservoir in NHPS and humans.
Aim 2: To define drivers of clonal expansion and persistence of the replication-competent viral reservoir in NHPS and humans to enhance reservoir control and elimination.

Focus 2: Novel Strategies for Sustained Virus Remission
Aim 1: To evaluate innovative immune engineering strategies that provide long-term T cell or Env-directed immune control, including therapeutic vaccines, CAR-T cells, and engineered B cells.
Aim 2: To combine approaches that augment humoral and cellular immune responses to achieve sustained immunosurveillance and long-term ART-free virologic control.

Focus 3: Novel Strategies for Virus Eradication
Aim 1: To evaluate innovative strategies for rapid elimination of the majority of the viral reservoir, including improved latency-reversing agents (LRAs) combined with broadly neutralizing antibodies (BNABs), activated NK cells, and CAR-T cells.
Aim 2: To combine the most effective approach to rapidly eliminate the majority of the viral reservoir with sustained immunosurveillance to eliminate the residual viral reservoir.

Management and Operations (MO) Section

Community Engagement (CE) Section

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

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 18563% from $125,000 to $23,329,181.