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Rapid selection of a human monoclonal antibody that potently neutralizes SARS-CoV-2 in two animal models

By Wei Li, Aleksandra Drelich, David R. Martinez, Lisa Gralinski, Chuan Chen, Zehua Sun, Alexandra Schäfer, Sarah R. Leist, Xianglei Liu, Doncho Zhelev, Liyong Zhang, Eric C. Peterson, Alex Conard, John W. Mellors, Chien-Te Tseng, Ralph S Baric, Dimiter S Dimitrov

Posted 14 May 2020
bioRxiv DOI: 10.1101/2020.05.13.093088

Effective therapies are urgently needed for the SARS-CoV-2/COVID19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from eight large phage-displayed Fab, scFv and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. One high affinity mAb, IgG1 ab1, specifically neutralized replication competent SARS-CoV-2 with exceptional potency as measured by two different assays. There was no enhancement of pseudovirus infection in cells expressing Fcγ receptors at any concentration. It competed with human angiotensin-converting enzyme 2 (hACE2) for binding to RBD suggesting a competitive mechanism of virus neutralization. IgG1 ab1 potently neutralized mouse ACE2 adapted SARS-CoV-2 in wild type BALB/c mice and native virus in hACE2 expressing transgenic mice. The ab1 sequence has relatively low number of somatic mutations indicating that ab1-like antibodies could be quickly elicited during natural SARS-CoV-2 infection or by RBD-based vaccines. IgG1 ab1 does not have developability liabilities, and thus has potential for therapy and prophylaxis of SARS-CoV-2 infections. The rapid identification (within 6 days) of potent mAbs shows the value of large antibody libraries for response to public health threats from emerging microbes. ### Competing Interest Statement Wei Li, Chuan Chen, Zehua Sun, Doncho Zhelev, John W. Mellors and Dimiter S. Dimitrov are coinventors of a patent, filed in the beginning of March by the University of Pittsburgh concerning the SARS-CoV-2 specific antibodies described in this paper.

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