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Principal Investigator: Ali Hassan Ellebedy
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2024
Award: $5,212,836
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
Core D: Antibody Core
Washington University (Ellebedy, Ali)
Respiroviruses, Rubulaviruses, Peribunyaviruses, and Phenuiviruses present major health burdens and have
pandemic potential. There are no preventative or therapeutic measures against most of the viruses in these
families. Infection with these families of viruses induces neutralizing antibodies against the viral surface envelope
glycoproteins, but key knowledge gaps remain with respect to the epitopes targeted by these antibody
responses. Dissecting protective antibody responses to identify the components that confer protection and the
components that are specific to particular viruses, virus families, or that recognize viruses across families is
critical to understanding how to most effectively target viruses that may emerge from these families in the future.
The central goal of the Antibody Core (Core D) is to generate large panels of recombinant monoclonal
antibodies (mAbs) targeting the surface envelope glycoproteins of two candidate prototype viruses from each of
these families. Structural and functional analyses of these mAbs will be carried out in collaboration with the four
Projects and Cores C-Structure and E-Correlates, and will aid in understanding the specificity of the human
B cell response against these viruses and inform rational immunogen design against their viral families.
Furthermore, Core D-Antibody will generate and identify combinations of potently neutralizing mAbs with
intrinsically high barriers to resistance in collaboration with each of the four Projects and Cores C-Structure
and E-Correlates for potential therapeutic use. Core D-Antibody will use both conventional single-cell sorting
and single-cell RNA sequencing-based approaches to generate the mAbs. Our core will adapt its B cell sorting
strategies to accommodate targeting new epitopes or utilizing altered antigen probes that are identified in the
structural and functional analyses. In summary, state-of-the-art technologies will be used to generate novel
human mAbs targeting each of the candidate prototype viruses, and their functional and structural
characterization will generate new insights for the development of rationally designed vaccine candidates and
potentially identify therapeutically useful mAb candidates to protect against these potentially emerging viral
families.
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