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; Eun-Hyung Lee, F; Nguyen, Doan C; Sanz, Ignacio; Martinez, David R; Rothlauf, Paul W; Bloyet, Louis-Marie; Whelan, Sean P J; 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 on the basis of 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 advanced antibody discovery platforms.