Core D: Antibody Core

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.