Fc-Dependent Mechanisms of Antibody-Mediated Killing (R01 Clinical Trial Not Allowed) | RFA AI 23 054

Opportunity Information: Apply for RFA AI 23 054

The National Institutes of Health (NIH) is offering an R01 grant opportunity titled "Fc-Dependent Mechanisms of Antibody-Mediated Killing (R01 Clinical Trial Not Allowed)" under Funding Opportunity Number RFA-AI-23-054 (CFDA 93.855). This is a discretionary health research grant focused on basic, non-clinical trial research aimed at clarifying how antibodies eliminate infected cells through Fc-dependent effector functions. In practical terms, the program is centered on what antibodies can do beyond neutralization, especially in situations where neutralizing antibodies are weak, hard to induce, or simply not enough to clear an infection.

The scientific emphasis is on Fc-mediated mechanisms of antibody function, particularly antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP). ADCC generally refers to immune cells recognizing antibody-coated target cells and killing them, while ADCP refers to immune cells engulfing and clearing antibody-tagged targets. The NOFO is looking for studies that dig into the underlying biology of these processes: what molecular interactions matter, which immune cell types drive the effect, how Fc receptors and downstream signaling shape outcomes, and what antibody features (such as isotype/subclass, Fc glycosylation patterns, affinity/avidity, epitope specificity, and geometry of binding) influence killing or clearance.

A key deliverable NIH is signaling is the generation of foundational data sets and practical tools that help predict Fc-mediated killing activity by antibodies. That includes work that can lead to better assays, reference standards, or analytic frameworks that make Fc-effector performance more measurable and more comparable across studies. The larger goal is to make it easier to identify, design, and optimize antibodies or immune responses that reliably drive Fc-dependent clearance, thereby accelerating therapeutic monoclonal antibody development and informing vaccine or vaccine-adjuvant strategies that intentionally elicit these kinds of functional antibody responses.

This opportunity is explicitly "Clinical Trial Not Allowed," meaning the supported work should remain in the basic research domain (for example, mechanistic studies, preclinical models, in vitro systems, and method development) rather than testing interventions in human participants as a clinical trial. The intent is to strengthen the mechanistic foundation so later-stage translational efforts can be guided by clearer, predictive understanding of Fc-driven effector functions.

The applicant pool is broad. Eligible applicants include a wide range of U.S. public entities (state, county, city/township governments, special districts, independent school districts, and public housing authorities), tribal governments and tribal organizations, and higher education institutions (public/state-controlled and private). Nonprofits with or without 501(c)(3) status are eligible, as are for-profit organizations (other than small businesses) and small businesses. The NOFO also calls out additional eligible applicant categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, and non-U.S. entities (foreign organizations) as well as regional organizations.

Key administrative details provided include an original application closing date of 2024-01-26, with an award ceiling listed as $300,000. The opportunity was created on 2023-09-26. Overall, the NOFO is positioning Fc-effector biology as a critical piece of the immunology toolkit for infectious disease control, with an emphasis on generating broadly useful mechanistic insights and predictive capabilities that can be carried forward into antibody therapeutics and next-generation vaccine design.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Fc-Dependent Mechanisms of Antibody-Mediated Killing (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 2023-09-26.
• Applicants must submit their applications by 2024-01-26. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $300,000.00 in funding.
• 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 RFA AI 23 054

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: