Epitope focusing to the receptor binding motif for a universal coronavirus vaccine

Project Summary There is urgent need for the development of effective countermeasures against the newly emerged novel coronavirus or "nCoV" (also known as COVID-19). The development of a "universal" coronavirus (CoV) vaccine would not only be effective against COVID-19 but, in theory, would protect against future, potential pandemic CoV strains. The pathway to such a vaccine will likely focus on the design of novel immunogens that elicit broadly neutralizing antibodies to conserved viral epitopes, such as the receptor binding site (RBS). Here we leverage our structure-based, "resurfacing" and glycan engineering immunogen design approaches for a universal influenza vaccine and extend it to COVID-19. Our ongoing studies for influenza demonstrate that our resurfaced, heterochimeric immunogen approach substantially increased the overall frequency of elicited RBS-directed responses and our glycan engineering approach could effectively focus the immune response to a novel, conserved influenza hemagglutinin epitope; we envision that implementing comparable immunogen design approaches for COVID-19 specifically focusing to its receptor-binding interface epitope would yield similar results. We intend to use this Administrative Supplement to generate preliminary data to show the efficacy of our approach for a COVID-19 vaccine, and to optimize the vaccine regimen in the murine model; the data generated here will form the basis for future studies for a universal CoV vaccine.