Core C: Viral Evolution

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.