Fc-Dependent Mechanisms of Antibody-Mediated Killing (U01 Clinical Trial Not Allowed) | RFA AI 18 042

Opportunity Information: Apply for RFA AI 18 042

This opportunity, titled "Fc-Dependent Mechanisms of Antibody-Mediated Killing (U01 Clinical Trial Not Allowed)" (RFA AI 18 042), is a National Institutes of Health program run through NIAID that funds mechanistic immunology research on how antibodies eliminate target cells through their Fc regions. The central focus is not on testing an intervention in people, but on building a clearer, evidence-based understanding of how Fc-driven effector functions work when antibodies tag infected cells, malignant or otherwise aberrant cells, or immune cells that are contributing to disease in conditions like autoimmunity and allergy. The broader aim is to generate knowledge that can be used to design better antibody therapies that intentionally deplete harmful cell populations and to guide vaccine strategies toward antibody responses that are especially good at recruiting Fc-dependent killing.

The science emphasis is on antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP), evaluated both in vitro and in vivo. Projects are expected to identify and define the variables that control how efficiently these processes occur. In practical terms, that means studies that disentangle how factors such as antibody isotype and subclass, Fc glycosylation patterns, Fc receptor engagement, target antigen density and distribution, immune cell type and activation state, tissue environment, cytokine milieu, and other host or pathogen variables change the outcome. The FOA is oriented toward rigorous mechanistic models rather than purely descriptive findings, with the expectation that funded teams will contribute results that can be integrated into predictive frameworks for Fc-mediated killing and clearance.

The award mechanism is a U01 cooperative agreement, which signals a more active programmatic role for NIH compared to a standard research grant. Investigators funded under this FOA are expected to participate in annual Program Progress and Steering Committee meetings, present their progress to other awardees and NIAID staff, and engage in cross-project coordination. A key purpose of these meetings is to accelerate the field by encouraging collaboration, sharing insights and methods, and building mechanistic models that reflect the combined findings across the program rather than isolated results from a single lab. The cooperative structure is intended to move the science forward faster by aligning efforts and reducing duplication, especially in an area where assay design, comparability, and interpretation can vary widely across groups.

From an outcomes perspective, NIAID is looking for work that will directly inform the next generation of ablative antibody therapeutics, meaning antibodies deliberately engineered or selected to remove specific cell populations through Fc-driven effector functions. At the same time, the program highlights vaccine relevance: if researchers can clarify what makes antibodies particularly effective at ADCC or ADCP, vaccine developers may be able to design immunogens or regimens that preferentially elicit those kinds of functional antibody responses. In short, the opportunity sits at the intersection of basic mechanism, translational antibody engineering, and immune-response shaping for vaccines, while still remaining non-clinical in terms of human trials.

Administratively, the FOA is categorized as discretionary funding and uses the cooperative agreement instrument under the health activity category, with CFDA number 93.855. The listed award ceiling is $300,000. The original closing date provided is 2019-02-01, and the FOA was created on 2018-10-05. It is also explicitly paired with a companion announcement that uses the R21 mechanism (PA-19-xxx), positioned for higher-risk or higher-reward projects that may have less preliminary data or that rely heavily on existing datasets, whereas the U01 mechanism is typically better suited to more developed projects that fit the cooperative, coordinated program structure.

Eligibility is broad and includes many types of domestic applicants such as state, county, and local governments; public and private institutions of higher education; independent school districts; special district governments; federally recognized tribal governments; tribal organizations; public housing authorities; nonprofit organizations with or without 501(c)(3) status; for-profit organizations (including small businesses); and other categories. The FOA also explicitly calls out additional eligible applicant types, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISISs, Hispanic-serving Institutions, HBCUs, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, and non-U.S. entities such as foreign organizations and regional organizations. Overall, the opportunity is designed to pull in a diverse set of research performers capable of contributing strong mechanistic immunology and antibody effector-function science within a coordinated NIAID program.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Fc-Dependent Mechanisms of Antibody-Mediated Killing (U01 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 2018-10-05.
• Applicants must submit their applications by 2019-02-01. (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 18 042

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