Potent neutralization of SARS-CoV-2 in vitro and in an animal model by a human monoclonal antibody

Li, W.; Drelich, A.; Martinez, D. R.; Gralinski, L. E.; Chen, C.; Sun, Z.; Liu, X.; Zhelev, D. V.; Zhang, L.; Peterson, E. L.; Conard, A.; Mellors, J. W.; Tseng, C.-T.; Baric, R. S.; Dimitrov, D. S.

doi:10.1101/2020.05.13.093088

bioRxiv · 10.1101/2020.05.13.093088

Potent neutralization of SARS-CoV-2 in vitro and in an animal model by a human monoclonal antibody

Li, W.·Drelich, A.·Martinez, D. R.·Gralinski, L. E.·Chen, C.·Sun, Z.·Liu, X.·Zhelev, D. V.·Zhang, L.·Peterson, E. L.·Conard, A.·Mellors, J. W.·Tseng, C.-T.·Baric, R. S.·Dimitrov, D. S.

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Abstract

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 Fc{gamma} 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.

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Li, W., Drelich, A., Martinez, D. R., Gralinski, L. E., Chen, C., Sun, Z., Liu, X., Zhelev, D. V., Zhang, L., Peterson, E. L., Conard, A., Mellors, J. W., Tseng, C.-T., Baric, R. S., Dimitrov, D. S.. 2020-05-14. Potent neutralization of SARS-CoV-2 in vitro and in an animal model by a human monoclonal antibody. https://doi.org/10.1101/2020.05.13.093088

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