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Abstract
Influenza A viruses (IAVs) pose a significant challenge worldwide, causing respiratory disease for 9 to 41 million individuals every year within the United States. The current seasonal vaccine targets the hemagglutinin (HA) glycoprotein to elicit an antibody response, and is the current countermeasure against this pathogen. However, the antibody response elicited by seasonal vaccination is only protective for a single season due to viral antigenic variation through mechanisms of antigenic drift and antigenic shift. Therefore, to expand antibody protection, a universal influenza vaccine called COBRA, for computationally optimized broadly reactive antigen, has been investigated. This approach combines wild-type HAs into a single COBRA HA immunogen through computational consensus building to expand antibody breadth to multiple strains.
Despite multiple reports showing the efficacy of the COBRA approach, the epitopes targeted by this vaccine have not been fully characterized in humans or animal models. This gap in knowledge could inform further vaccine optimization efforts to elicit antibodies against highly conserved epitopes. Therefore, to characterize this aspect of the COBRA approach, we evaluated the pre-existing monoclonal antibody (mAb) response to COBRA HA immunogens after seasonalvaccination. We further assessed the epitopes targeted by adjuvanted and multimeric COBRA HA vaccination. Finally, we also defined the structural features of historic as well as lead COBRA vaccine candidates in the context of epitope elucidation. Through these studies, we found novel mAb epitopes which could then be used to characterize vaccine-elicited antibody breadth in animal models. In summary, this work provides a foundation to further advance the COBRA vaccine from an epitope-focused perspective.
Despite multiple reports showing the efficacy of the COBRA approach, the epitopes targeted by this vaccine have not been fully characterized in humans or animal models. This gap in knowledge could inform further vaccine optimization efforts to elicit antibodies against highly conserved epitopes. Therefore, to characterize this aspect of the COBRA approach, we evaluated the pre-existing monoclonal antibody (mAb) response to COBRA HA immunogens after seasonalvaccination. We further assessed the epitopes targeted by adjuvanted and multimeric COBRA HA vaccination. Finally, we also defined the structural features of historic as well as lead COBRA vaccine candidates in the context of epitope elucidation. Through these studies, we found novel mAb epitopes which could then be used to characterize vaccine-elicited antibody breadth in animal models. In summary, this work provides a foundation to further advance the COBRA vaccine from an epitope-focused perspective.