Targeting Cell Surface HIV Envelope for Cell Elimination (R01 Clinical Trial Not Allowed)

The National Institutes of Health (NIH), under the Department of Health and Human Services, through its sub-agency, the National Institute of Allergy and Infectious Diseases (NIAID), has released a Notice of Funding Opportunity (NOFO) titled "Targeting Cell Surface HIV Envelope for Cell Elimination (R01 Clinical Trial Not Allowed)". This initiative seeks to advance research in the area of HIV-1, specifically focusing on the envelope glycoprotein (Env), which is the only viral protein expressed on the surface of infected cells. The funder supports investigations into Env cell surface expression, the structural mechanisms of biologic-mediated cell killing, and strategies to improve immune system targeting and elimination of Env-expressing cells. The ultimate goal is to inform the development of new immunotherapies and vaccines aimed at HIV-1 prevention and cure. The research funded under this opportunity will explore both fundamental and translational science. Areas of emphasis include characterization of Env density and distribution on primary infected cells, the effect of stimulants like cytokines on surface Env levels, and the host cell pathways involved in Env expression and trafficking. Investigators are encouraged to identify small molecules that manipulate Env surface expression and study host factors influencing these mechanisms. Proposals may also focus on developing or improving biologics such as antibodies, T/NK cell engagers, and CAR T/NK cells to increase the efficacy of killing HIV-infected cells. Importantly, the structural mechanisms underpinning biologic-mediated cell killing must be considered, particularly for cells exhibiting low-level surface Env expression. This grant opportunity supports R01 mechanisms and does not allow clinical trials. Application budgets are not capped but must reflect actual project needs, and projects may span up to five years. Applicants requesting $500,000 or more in direct costs in any year must contact the relevant NIH Scientific/Research contact at least six weeks prior to application. The number of awards will depend on the availability of NIH appropriations and the volume of meritorious applications. While the program does not mandate cost sharing, all applications must include a Data Management and Sharing Plan. This reflects NIH’s ongoing commitment to transparency and responsible stewardship of federally funded research data. Eligible applicants include a broad spectrum of institutions such as higher education institutions (both public and private), nonprofits, for-profit organizations, tribal governments, and foreign entities. Specifically, the eligibility list includes state, county, city, and special district governments, as well as U.S. territories, housing authorities, and faith-based or community-based organizations. There are no stated geographic limitations; non-domestic organizations and foreign components of U.S. institutions are eligible to apply. However, all applicants must complete specific registrations, including with SAM.gov, eRA Commons, and Grants.gov, prior to submission. Applications for this NOFO are accepted according to the NIH standard AIDS due dates, beginning May 7, 2025. Additional due dates recur every four months (May, September, January) through January 2028. Each cycle includes merit review, advisory council review, and anticipated award dates. For instance, the May 7, 2025 deadline will result in December 2025 start dates, while subsequent rounds follow similar timelines. While there are no required pre-application steps such as letters of intent, applicants are encouraged to submit early to allow for error correction and application review through NIH’s eRA Commons. Applications must follow the SF424 (R&R) and PHS 398 formats, as specified in the NIH Application Guide. This includes sections on the research strategy, environment, letters of support, and appendices. Specific emphasis is placed on demonstrating how the research will increase understanding of Env surface dynamics and improve the structural design of therapeutic biologics. All applications will be peer-reviewed based on significance, innovation, approach, investigator qualifications, and environment. Contact information for submission includes Dr. Yan Zhou (Scientific/Research Contact) and Robert Kirker (Grants Management Contact) at NIAID.

Focus on the structural basis for biologic-mediated cell killing and Env density. Use complementary methods and validate in primary models. No clinical trials.