B-Cell Epitope Discovery and Mechanisms of Antibody Protection: Genetic and Structural Basis for Influenza Neutralization

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This contract supports the identification of human B cell epitopes derived from influenza hemagglutinin, coupled with basic studies to understand protective immunity mediated by antibodies and, when applicable, pathological consequences of antibody responses. Milestones include 1) epitope identification; 2) epitope validation that must include in vitro evaluation using human samples; 3) submission of epitope data, computer software, and structural data to the Immune Epitope Database and Analysis Resource; and 4) studies to help understand the mechanisms of protection or pathogenesis elicited by antibodies associated with the newly identified epitopes. The goal of this contract is to comprehensively map the epitopes of human protective antibodies that bind to the neuraminidase protein and to broadly protective sites of influenza hemagglutinin. The purpose is to identify protective antigens and epitopes, with the long-term goal of translating the data for monitoring epitope-specific responses in experimental vaccine studies, rational design of structure-based epitope vaccines, and use of isolated human monoclonal antibodies (mAb) isolated as developmental tools for development future as prophylactic and therapeutic molecules in humans.