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

• Published in: Nature Medicine Vol. 26; no. 9; pp. 1422 - 1427
• Main Authors: 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.
• Format: Journal Article Magazine Article
• Language: English
• Published: New York Nature Publishing Group US 01-09-2020; Nature Publishing Group
• Subjects: 631/250/2152/2153/1291; 631/326/596/4130; Antibodies; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - isolation & purification; Antibodies, Monoclonal - therapeutic use; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - isolation & purification; Betacoronavirus - drug effects; Betacoronavirus - immunology; Betacoronavirus - pathogenicity; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical trials; Coronavirus Infections - drug therapy; Coronavirus Infections - immunology; Coronavirus Infections - virology; Coronaviruses; COVID-19; Cross-reactivity; Humans; Identification and classification; Immunological research; Infectious Diseases; Letter; Life Sciences; Metabolic Diseases; Microbiology and Parasitology; Molecular Medicine; Monoclonal antibodies; Neurosciences; Pandemics; Pneumonia, Viral - drug therapy; Pneumonia, Viral - immunology; Pneumonia, Viral - virology; Protein Binding; Proteins; RNA viruses; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - antagonists & inhibitors; Spike Glycoprotein, Coronavirus - immunology; Spike protein; Viral diseases; Viral proteins; Virology; Viruses; United States; Spike Glycoprotein; Antibody; SARS - CoV - 2
• ISSN: 1078-8956; 1546-170X; 1546-170X; 1744-7933
• DOI: 10.1038/s41591-020-0998-x

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
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. 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.