Core C: Viral Evolution

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Principal Investigator: Jesse D Bloom
Organization: UNIVERSITY OF WASHINGTON
Fiscal Year: 2022
Award: $1,225,278
Funding agency: National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY – CORE C: VIRAL EVOLUTION
The Viral Evolution Core will develop tools to inform the engineering of vaccines that broadly target
coronaviruses that pose a pandemic risk. To do this, the core will use deep mutational scanning to define the
biochemical and functional properties of RBDs and spikes across the full evolutionary span of sarbecoviruses
and merbecoviruses, and systematically map how these proteins are targeted by vaccine-elicited antibody
immunity. In the first aim, we will measure the receptor-binding properties of all known sarbecovirus and
merbecovirus RBDs to identify key strains of interest and inform the development of animal models (Core B:
Virology, Baric). In the second aim, we will develop a system to measure how all mutations to the spikes from
key strains affect cell entry, thereby identifying functionally constrained epitopes to target with vaccines. In the
third aim, we will use the RBD and spike libraries to quantify the binding breadth and robustness to mutations
of vaccine elicited monoclonal and polyclonal antibodies, thereby providing direct functional readouts to rapidly
assess candidate vaccines and inform their further engineering.

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