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

NIH Pandemic-Era Grants

Pandemic Era Grants

2021

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Principal Investigator: Aaron Gregory Schmidt
Organization: MASSACHUSETTS GENERAL HOSPITAL
Fiscal Year: 2021
Award: $239,867
Funding agency: National Institute of Allergy and Infectious Diseases

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.

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