Epitope focusing by molecular grafting of subdominant epitopes to achieve a universal-influenza vaccine

There is urgent need for the development of effective countermeasures against the newly emerged novelcoronavirus 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 novelimmunogens that elicit broadly neutralizing antibodies to conserved viral epitopes, such as the receptorbinding site (RBS). Here we leverage our structure-based, "resurfacing" and glycan engineeringimmunogen design approaches for a universal influenza vaccine and extend it to COVID-19. Our ongoingstudies for influenza demonstrate that our resurfaced, heterochimeric immunogen approach substantiallyincreased the overall frequency of elicited RBS-directed responses and our glycan engineering approachcould effectively focus the immune response to a novel, conserved influenza hemagglutinin epitope; weenvision that implementing comparable immunogen design approaches for COVID-19 specificallyfocusing to its receptor-binding interface epitope would yield similar results. We intend to use thisAdministrative Supplement to generate preliminary data to show the efficacy of our approach for aCOVID-19 vaccine, and to optimize the vaccine regimen in the murine model; the data generated herewill form the basis for future studies for a universal CoV vaccine.