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

Frequently Asked Questions (FAQs)

What is the title and number of this funding opportunity?

The opportunity is titled "Targeting Cell Surface HIV Envelope for Cell Elimination (R01 Clinical Trial Not Allowed)" and the opportunity number is PAR 25-300.

Which agency is sponsoring this grant?

The sponsoring agency is the National Institutes of Health (NIH).

What type of grant mechanism is being offered?

This is an NIH R01 discretionary research grant.

What is the overall goal of the funded research?

The goal is to support basic and translational studies that improve understanding and practical use of HIV-1 Envelope (Env) on the surface of infected cells as a target for recognition and elimination of infected cells. The intended payoff is knowledge and enabling tools that can support next-generation immunotherapies and targeted vaccine concepts for HIV-1 prevention and especially durable cure strategies that require eliminating infected cells that persist despite therapy.

What is the central scientific idea behind this opportunity?

The central idea is to better understand when and how HIV-1 Env appears on the cell surface during infection, how immune or engineered biologics recognize Env in its native membrane context, and how that recognition can be translated into efficient killing or clearance of infected cells.

Why is HIV-1 Env a focus of this program?

Env is treated as a vulnerable and targetable feature on the surface of infected cells. This funding opportunity is designed to close the gap between knowing Env exists and being able to consistently use it as a practical "handle" to identify and remove infected cells.

What research themes does the NOFO emphasize?

The NOFO emphasizes three linked themes: (1) investigation of HIV-1 Env cell surface expression, (2) structural mechanisms of biologic-mediated cell killing, and (3) development of novel approaches that enhance recognition and elimination of Env-expressing infected cells.

What does "investigation of HIV-1 Env cell surface expression" mean in this context?

It refers to studies on what controls Env 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.

What is meant by "structural mechanism of biologic-mediated cell killing"?

It means mechanistic work that links the structure and presentation of Env, and Env-antibody or Env-biologic interactions, to downstream immune effector functions that eliminate infected cells. Examples described in the opportunity include understanding how binding angles, epitopes, conformational states, or glycan patterns affect the ability of antibodies or other biologics to trigger cytotoxic processes.

What kinds of "biologics" are implied by the opportunity description?

Based on the description, biologics include immune or engineered biologics that can recognize Env in its native membrane context, including antibodies and other Env-targeting biologic modalities, with an emphasis on how binding translates into effector functions that clear or kill infected cells.

What does the NOFO mean by "development of novel approaches" to improve elimination of infected cells?

It points to engineering and strategy development aimed at improving targeting, potency, breadth across HIV variants, or effectiveness in relevant biological contexts for recognizing and eliminating Env-expressing infected cells.

Is this opportunity focused on HIV prevention, HIV cure, or both?

Both. The description links Env-targeted killing to immunotherapies and targeted vaccines, and highlights durable cure strategies that require eliminating infected cells that persist despite therapy. It also notes prevention concepts that could prevent establishment of infection through more effective immune engagement.

How does this research relate to antiretroviral therapy (ART)?

The solicitation frames Env-targeted killing as a potential complement or extension to ART by addressing infected cells that persist despite therapy (often described as reservoirs) and by improving immune engagement that could help prevent infection establishment.

Are clinical trials allowed under this R01 opportunity?

No. The opportunity is explicitly labeled "Clinical Trial Not Allowed."

If clinical trials are not allowed, what kinds of studies are appropriate?

Projects should be preclinical or non-trial human studies, such as laboratory, computational, or ex vivo work, rather than interventional clinical studies that test outcomes in human participants.

What is the funding activity category for this opportunity?

The funding activity category is Health.

What is the CFDA number listed for this opportunity?

The CFDA number provided is 93.855.

Who is eligible to apply?

Eligibility is broad and includes many types of U.S. and non-U.S. organizations, including various government entities, institutions of higher education (public and private), tribal governments and tribal organizations, housing authorities, nonprofits (with and without 501(c)(3) status, excluding institutions of higher education in those categories), for-profit organizations (including small businesses), and additional categories highlighted in the NOFO.

Can non-U.S. (foreign) organizations apply?

Yes. The NOFO includes non-domestic (non-U.S.) entities/foreign organizations among eligible applicants.

Are U.S. territories or possessions eligible to apply?

Yes. U.S. territories or possessions are included in the listed eligible applicant categories.

Are tribal entities eligible to apply?

Yes. The eligible applicant list includes federally recognized Native American tribal governments, Native American tribal organizations other than federally recognized tribal governments, and Indian/Native American tribal governments that are not federally recognized.

Are minority-serving institutions specifically called out as eligible?

Yes. The NOFO highlights Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, HBCUs, and TCCUs among additional eligible applicant categories.

Are faith-based or community-based organizations eligible?

Yes. Faith-based or community-based organizations are included in the additional eligible applicant categories.

Are federal agencies eligible to apply?

Yes. Eligible federal agencies are listed among additional eligible applicant categories.

Is there an award ceiling listed in the provided information?

No. An award ceiling is not specified in the provided source data.

Is the expected number of awards provided?

No. The expected number of awards is not specified in the provided source data.

What should applicants do if budget limits or project period expectations are not shown here?

The provided information indicates that when award ceilings, expected award counts, or other administrative constraints are not specified, applicants should consult the full announcement for budget guidance, project period expectations, and any institute- or program-specific limits or priorities.

What is the original closing date listed for this opportunity?

The original closing date listed is 2028-01-07.

When was this opportunity created?

The opportunity was created on 2024-12-02.

What does the program ultimately aim to produce?

It aims to strengthen the scientific foundation for Env-directed clearance strategies by mapping how Env is presented on infected cells, clarifying mechanistic and structural bases for biologic-triggered killing, and creating or improving targeting approaches that make elimination of Env-expressing cells more reliable, with the intent to enable translation into immunotherapies and vaccine concepts.