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[Preprint]. 2020 May 13:2020.05.12.091462. [Version 1] doi: 10.1101/2020.05.12.091462

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

Seth J Zost, Pavlo Gilchuk, Rita E Chen, James Brett Case, Joseph X Reidy, Andrew Trivette, Rachel S Nargi, Rachel E Sutton, Naveenchandra Suryadevara, Elaine C Chen, Elad Binshtein, Swathi Shrihari, Mario Ostrowski, Helen Y Chu, Jonathan E Didier, Keith W MacRenaris, Taylor Jones, Samuel Day, Luke Myers, F Eun-Hyung Lee, Doan C Nguyen, Ignacio Sanz, David R Martinez, Ralph S Baric, Larissa B Thackray, Michael S Diamond, Robert H Carnahan, James E Crowe
PMCID: PMC7263562  PMID: 32511414

Abstract

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 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.

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