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

Seth J. Zost, P. Gilchuk, Rita E. Chen, J. Case, Joseph X. Reidy, Andrew Trivette, Rachel S. Nargi, Rachel E. Sutton, Naveenchandra Suryadevara, Elaine C. Chen, E. Binshtein, Swathi Shrihari, M. Ostrowski, H. Chu, Jonathan E. Didier, K. Macrenaris, Taylor Jones, Samuel B. Day, Luke Myers, F. Eun-Hyung Lee, D. Nguyen, I. Sanz, D. R. Martinez, P. W. Rothlauf, Louis-Marie Bloyet, S. Whelan, R. Baric, L. Thackray, M. Diamond, R. Carnahan, J. Crowe

Nature Medicine, 2020

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 date 1 , 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. A platform for rapid antibody discovery enabled the isolation of hundreds of human monoclonal antibodies against SARS-CoV-2 and the prioritization of potent antibody candidates for clinical trials in patients with COVID-19.

Cited by 117 publications.

Field of study: Medicine

10.1038/s41591-020-0998-x