Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein

Zost, Seth J.; Gilchuk, Pavlo; Chen, Rita E.; Case, James Brett; Reidy, Joseph X.; Trivette, Andrew; Nargi, Rachel S.; Sutton, Rachel E.; Suryadevara, Naveenchandra; Chen, Elaine C.; Binshtein, Elad; Shrihari, Swathi; Ostrowski, Mario; Chu, Helen Y.; Didier, Jonathan E.; MacRenaris, Keith W.; Jones, Taylor; Day, Samuel; Myers, Luke; Lee, F. Eun-Hyung; Nguyen, Doan C.; Sanz, Ignacio; Martinez, David R.; Baric, Ralph S.; Thackray, Larissa B.; Diamond, Michael S.; Carnahan, Robert H.; Crowe, James E.

Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes based on their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of new antibody discovery methodologies.