NIH R01: Engineering Durable HIV Vaccine Responses

Funding Opportunity Number: RFA-AI-24-025

Deadline: October 9, 2024


HIV vaccines will ultimately require broad and durable immunity. Durability of vaccine responses varies widely, with estimated half-lives ranging from months to decades. Yellow fever and smallpox vaccines confer life-long protection, while vaccines for influenza and SARS-CoV-2, mutation-prone viruses, require frequent boosting. Multiple properties of the vaccine and target virus influence the durability of a vaccine response: viral diversity, incubation period, antigen valence, vaccine platform, adjuvant, route of administration, and others. For example, a 60-mer nanoparticle of an engineered outer domain HIV Env immunogen induced larger germinal centers and more sustained antigen-specific antibody responses than a 4-mer nanoparticle in a murine model. To engineer or induce a durable vaccine response, we must clarify factors generating durable immunity, immune responses associated with durable immunity, and methods for measuring durable immunity. This Notice of Funding Opportunity (NOFO) solicits applications addressing these areas through basic or applied research.

Research Objectives

The scientific objective of this NOFO is to support hypothesis-driven research to investigate and improve the durability of immune responses to candidate vaccines for HIV prevention. NIAID’s Division of AIDS seeks applications that propose research to 1) understand and define durable vaccine responses; 2) develop or improve methods to measure durable vaccine responses; and/or 3) engineer more durable vaccine responses. While vaccine durability is ideally defined in terms of protection from disease, for the purposes of this NOFO, durability consists of persistent immune responses, recall responses, and/or adaptive immune memory. Applications may include basic and applied research using human samples, and/or appropriate animal models.

Though clinical trials are not allowed, use of samples from clinical trials funded through other mechanisms and/or collaborations with groups performing clinical trials is highly encouraged. Studies in appropriate animal models, including small animals and NHPs, with HIV, SIV, and/or SHIV are allowed. Benchmarking durability using vaccines for infectious diseases other than HIV is allowed as appropriately justified. Applicants are encouraged to incorporate bioengineering approaches.

For more information, please see the opportunity webpage.