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Epitope-Paratope Characteristics and IgG1 Allostery in Fc-mediated Effector Function

$463,676R01FY2025AINIH

University Of Maryland Baltimore, Baltimore MD

Investigators

Abstract

Project Summary This project seeks to enhance our understanding of the mechanisms underpinning Fc-mediated effector functions in the context of infectious diseases. Despite the role of Fc-mediated effector functions in bridging adaptive and innate immunity to combat various pathogens, certain infectious agents have evolved to evade these immune responses, potentially exacerbating disease progression. To counter this, our research aims to dissect the intricacies of Fc-mediated effector functions specifically targeting a viral surface protein. Our proposal sets forth a comprehensive analysis of the factors influencing Fc-mediated effector mechanisms for a viral surface protein by leveraging our novel assays for Fc-mediated effector functions. This assay has been instrumental in establishing a correlation between immune protection in a number of immunization and antibody therapy studies. Through a detailed exploration of how antibodies that recognize this viral protein enhance Fc- mediated effector functions, we aim to elucidate the structural and functional parameters that can be “tuned” to develop new antibody-based preventions and therapies. Further, this project will provide new insights on how the human immune system protects against infections as well as maintaining immune balance to prevent autoimmune diseases. .

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