NIH/NIAID Funding Opportunity: Fc-Dependent Mechanisms of Antibody-Mediated Killing

Funding Opportunity Number: RFA-AI-23-054

Deadline: January 26, 2024


The purpose of this funding opportunity is to support basic research that will elucidate mechanisms of Fc-mediated antibody (Ab) functions, including but not limited to antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP). The goal of the program is to understand the parameters that influence Fc-mediated Ab functional efficiencies to inform the development of therapeutic monoclonal antibodies and prediction of epitopes that induce antibodies with Fc-dependent killing functions for incorporation into candidate vaccines. The latter would be particularly relevant for pathogens/vaccines that fail to consistently induce durable and protective neutralizing antibody responses.

Research Objectives and Scope

Projects should focus on, but are not limited to, the study of either the antigen-binding or Fc regions of antibodies. Studies may include examination of antibody post-translational modifications; anatomical locations and the maturation and activation status of effector cell types; expression patterns and genetic variation of effector cell FcRs; and antibody epitope characteristics that mediate efficient Fc-mediated killing activities.

Studies supported by this NOFO are expected to include one of the following, but are not limited to:

    • Defining the molecular mechanisms of protection mediated by non-neutralizing antibodies.
    • Evaluating contributions of effector cell types in human tissues – taking into account their availability, anatomical distribution, and phenotypic characteristics — to in vivo killing and therapeutic antibody efficacy.
    • Developing/refining ex vivo and in vivo models that accurately measure or serve as surrogates of human in vivo activity.
    • Fostering development and application of computational models to integrate prediction of FcR function/killing with epitope immunogenicity.
    • Informing design of vaccines that elicit both protective neutralizing and non-neutralizing antibody activities.


For more information, please see the funding opportunity website.