Immunogen Design for SARS-CoV-2

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The SARS-CoV-2 spike is the basis of the majority of 1st-generation COVID-19 vaccines, which are currently in Phase III testing or just receiving FDA approval. We anticipate the immunogenicity from wild-type or "2P"-stabilized spikes may not be optimal, and are currently working to improve. In specific, we and others are working to define spike-based mechanisms by which SARS-CoV-2 evades the humoral immune response as well as to identify antibodies that are effective at preventing SARS-CoV-2 infection. Based on this developing insight, we are using antibody-guided structure-based design to develop spike-based immunogens with these immune-evading mechanisms disabled so as to preferentially elicit potently neutralizing antibodies. We have also begun to couple these spike-based immunogens to highly immunogenic carrier proteins or self-assembling nanoparticles, as multivalent display often yields substantially higher immunogenicity than that of a single spike trimer.