P01AI189362

Translating germline-targeting HIV Env SOSIP immunization of infants: Targeting bnAbs in early life - Abstract – Overall despite decades of research and millions of global infections and deaths, we remain without an effective vaccine against HIV.

Traditional vaccine approaches have failed to induce broadly neutralizing antibodies (bnAbs), crucial for protection against diverse HIV strains.

The primary goal of next-generation HIV vaccines is to stimulate B cell lineages capable of producing bnAbs.

Recent successes in this realm involve structurally designed immunogens, such as the BG505 germline-targeting (GT1.1) HIV envelope SOSIP trimer, which mimics native viral envelope structures and engages bnAb precursor lineages.

While promising, achieving bnAb responses in plasma, even at low levels, remains unachieved in the adult populations where it has been tested.

Children living with HIV exhibit faster development and more polyclonal bnAb responses compared to adults, suggesting the potential success of early-life vaccination strategies targeting bnAb responses.

Our preclinical studies in nonhuman primates have indicated that infant rhesus macaques more frequently develop bnAb precursor responses following BG505 GT1.1 SOSIP trimer immunization, with robust autologous virus neutralization and early evidence of heterologous virus neutralization in plasma.

This vaccine has also shown promise in adult human clinical trials in eliciting “on target” vaccine responses, without any safety concerns.

While the early life immune system may offer benefits to this vaccine regimen for achieving its immunologic goals, the dosing, intervals, and potential interactions with pre-existing antibodies and other childhood vaccines is unknown, limiting the development of an optimal infant phase 1 trial.

Thus, this program aims to design and systematically test the optimal regimen of BG505 GT1.1 SOSIP trimer vaccine series as a safe and effective pediatric immunogen for eliciting lifelong bnAb responses.

Specific aims include: Aim 1: Determining the optimal pediatric formulation and dose, Aim 2: Aligning immunization intervals with childhood vaccine schedules and assessment of persistence of responses into adolescence, and Aim 3: Assessing the impact of maternal antibodies and passive immunization with bnAbs on vaccine immunogenicity and efficacy.

By leveraging preclinical models to assess safety, regimen, and persistence into adulthood, this program seeks to overcome regulatory hurdles that will pave the way for optimized infant HIV vaccine trials.

Successful induction of bnAbs via early-life vaccination could revolutionize HIV prevention efforts, offering hope for a future without the burden of the HIV epidemic.

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 United States

State-Wide

NIAID Investigator Initiated Program Project Applications (P01 Clinical Trial Not Allowed) (PAR-22-225)