The National Institutes of Health (NIH), through the National Institute of Allergy and Infectious Diseases (NIAID), has reissued the funding opportunity titled “Innovation for HIV Vaccine Discovery (R01 Clinical Trial Not Allowed)” under Notice of Funding Opportunity (NOFO) Number PAR-23-169. The purpose of this opportunity is to support high-risk, high-impact early discovery research on novel HIV vaccine approaches, which focus on preventing HIV acquisition or reducing ongoing infection. This FOA encourages exploratory strategies that have not been previously tested, aiming to stimulate innovative and transformative advances in HIV vaccine research. Importantly, the funding mechanism uses a “Go/No-Go” evaluation criterion, which determines if the project progresses beyond the first two years based on achieving specific, pre-negotiated milestones.

This NOFO specifically targets early-stage vaccine development research, with an emphasis on leveraging scientific advances from COVID-19 vaccine research to address the unique challenges in HIV vaccine development. The ultimate goal is to improve understanding of immune responses, such as broad T-cell and B-cell activation, as well as innate immunity, to either prevent initial infection or control established infection and eliminate latent reservoirs. Preliminary data are not required, making this funding opportunity particularly suitable for projects at a conceptual stage that aim to push the boundaries of current HIV vaccine research paradigms.

Proposals should include novel approaches, such as developing innovative immunogens or immunization strategies that focus on inducing durable cellular and humoral immune responses against HIV. Research may include investigating new delivery platforms, novel antigen processing mechanisms, and immune responses targeting relevant anatomical sites like mucosal tissues. Studies using preclinical models, such as simian-tropic HIV, SIV, or SHIV, are strongly encouraged, as are projects that utilize advanced functional -omics technologies or machine learning tools. Importantly, research proposals must include specific "Go/No-Go" decision criteria that define measurable, quantitative milestones to be achieved by the end of Year 2, which will dictate continued funding for the latter two years.

The anticipated number of awards is two to four, with a total funding amount of $2 million available for fiscal year 2024. The project period is up to four years, with a maximum budget of $350,000 per year in direct costs. However, applicants can request an additional $150,000 in years involving research with nonhuman primates (NHPs) or humanized mice, with appropriate justification.

Eligible applicants include U.S. and non-U.S. institutions, including higher education institutions, non-profit organizations, and for-profit organizations such as small businesses. Foreign institutions and non-domestic components of U.S. organizations are also eligible to apply. Applications must conform to the NIH SF424 (R&R) application guidelines, including specific instructions for Go/No-Go decision criteria, and applicants are encouraged to submit proposals before the deadline to ensure timely corrections.

The application deadlines are August 2 of each year through 2025. Applicants are expected to include a detailed research strategy with clear Go/No-Go milestones, collaboration letters of support, and a comprehensive data management plan. Importantly, applications proposing clinical trials or incremental improvements of existing vaccine platforms will not be considered responsive and will not be reviewed.

For more detailed guidance on preparing and submitting applications, potential applicants are encouraged to contact NIAID program officials and review the application requirements on the NIH’s submission platforms such as ASSIST and Grants.gov.