Targeting Cell Surface HIV Envelope for Cell Elimination (R01 Clinical Trial Not Allowed) | PAR 25 300

Opportunity Information: Apply for PAR 25 300

This funding opportunity, titled "Targeting Cell Surface HIV Envelope for Cell Elimination (R01 Clinical Trial Not Allowed)" (PAR 25-300), is a National Institutes of Health discretionary research grant that supports basic and translational studies focused on HIV-1 Envelope (Env) as a vulnerable, targetable feature on the surface of infected cells. The central idea is to better understand when and how Env appears on the cell surface during HIV infection, how immune or engineered biologics can recognize Env in its native membrane context, and how that recognition can be converted into efficient killing or clearance of infected cells. The ultimate goal is to generate knowledge and tools that push forward next-generation immunotherapies and targeted vaccine concepts aimed at HIV-1 prevention and, especially, durable cure strategies that require eliminating infected cells that persist despite therapy.

Scientifically, the NOFO emphasizes three linked themes. First is investigation of HIV-1 Env cell surface expression: what controls its presence, density, conformation, and exposure on infected cells, including how viral and host factors influence whether Env is visible to immune effectors or shielded from them. Second is the structural mechanism of biologic-mediated cell killing, meaning the opportunity is looking for mechanistic work that connects the structure and presentation of Env (and Env-antibody or Env-biologic interactions) to downstream immune effector functions that actually eliminate cells. This can include understanding how different binding angles, epitopes, conformational states, or glycan patterns influence the ability of antibodies or other biologics to trigger cytotoxic processes. Third is the development of novel approaches to enhance recognition and elimination of Env-expressing infected cells, which points to engineering and strategy development that improves targeting, potency, breadth across HIV variants, or effectiveness in relevant biological contexts.

In practical terms, the research supported here is meant to close the gap between simply knowing that Env exists and being able to consistently use it as a handle to find and remove infected cells. The solicitation frames Env-targeted killing as a path to immunotherapies and targeted vaccines, implying interest in approaches that could complement or extend antiretroviral therapy by addressing reservoirs or by preventing establishment of infection through more effective immune engagement. Because this is an R01 and explicitly "Clinical Trial Not Allowed," supported projects should be preclinical or non-trial human studies (for example, laboratory, computational, or ex vivo work) rather than interventional clinical studies that test an outcome in human participants.

Eligibility is broad and includes many types of U.S. and non-U.S. organizations. Eligible applicants span state, county, city/township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; Native American tribal organizations other than federally recognized tribal governments; public housing authorities and Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those categories); for-profit organizations other than small businesses; and small businesses. The NOFO also highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), eligible federal agencies, faith-based or community-based organizations, regional organizations, non-domestic (non-U.S.) entities/foreign organizations, U.S. territories or possessions, and Indian/Native American tribal governments that are not federally recognized.

Key administrative details from the source information include the funding activity category of Health, CFDA number 93.855, the sponsoring agency being the National Institutes of Health, and the original closing date listed as 2028-01-07. The opportunity was created on 2024-12-02. An award ceiling and expected number of awards are not specified in the provided source data, which typically means applicants should consult the full announcement for budget guidance, project period expectations, and any institute- or program-specific limits or priorities.

Overall, this NOFO is aimed at strengthening the scientific foundation for Env-directed clearance strategies by funding work that maps how Env is presented on infected cells, clarifies the mechanistic and structural basis for biologic-triggered killing, and invents or improves targeting approaches that make elimination of Env-expressing cells more reliable. The intended payoff is actionable insight and enabling technologies that can be translated into HIV immunotherapies and vaccine concepts designed to prevent infection or contribute to cure by reducing or eradicating infected cell populations.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Targeting Cell Surface HIV Envelope for Cell Elimination (R01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855.
• This funding opportunity was created on 2024-12-02.
• Applicants must submit their applications by 2028-01-07.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 25 300

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