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; Paul W. Rothlauf; Louis Marie Bloyet; Sean P.J. Whelan; Ralph S. Baric; Larissa B. Thackray; Michael S. Diamond; Robert H. Carnahan; James E. Crowe

doi:10.1038/s41591-020-0998-x

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 LeeDoan C. Nguyen, Ignacio Sanz, David R. Martinez, Paul W. Rothlauf, Louis Marie Bloyet, Sean P.J. Whelan, Ralph S. Baric, Larissa B. Thackray, Michael S. Diamond, Robert H. Carnahan, James E. Crowe

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323 Scopus citations

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 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.

Original language	English
Pages (from-to)	1422-1427
Number of pages	6
Journal	Nature medicine
Volume	26
Issue number	9
DOIs	https://doi.org/10.1038/s41591-020-0998-x
State	Published - Sep 1 2020

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Zost, S. J., Gilchuk, P., Chen, R. E., Case, J. B., Reidy, J. X., Trivette, A., Nargi, R. S., Sutton, R. E., Suryadevara, N., Chen, E. C., Binshtein, E., Shrihari, S., Ostrowski, M., Chu, H. Y., Didier, J. E., MacRenaris, K. W., Jones, T., Day, S., Myers, L., ... Crowe, J. E. (2020). Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein. Nature medicine, 26(9), 1422-1427. https://doi.org/10.1038/s41591-020-0998-x

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

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 date1,2. 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.",

author = "Zost, {Seth J.} and Pavlo Gilchuk and Chen, {Rita E.} and Case, {James Brett} and Reidy, {Joseph X.} and Andrew Trivette and Nargi, {Rachel S.} and Sutton, {Rachel E.} and Naveenchandra Suryadevara and Chen, {Elaine C.} and Elad Binshtein and Swathi Shrihari and Mario Ostrowski and Chu, {Helen Y.} and Didier, {Jonathan E.} and MacRenaris, {Keith W.} and Taylor Jones and Samuel Day and Luke Myers and {Eun-Hyung Lee}, F. and Nguyen, {Doan C.} and Ignacio Sanz and Martinez, {David R.} and Rothlauf, {Paul W.} and Bloyet, {Louis Marie} and Whelan, {Sean P.J.} and Baric, {Ralph S.} and Thackray, {Larissa B.} and Diamond, {Michael S.} and Carnahan, {Robert H.} and Crowe, {James E.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2020",

month = sep,

day = "1",

doi = "10.1038/s41591-020-0998-x",

language = "English",

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Zost, SJ, Gilchuk, P, Chen, RE, Case, JB, Reidy, JX, Trivette, A, Nargi, RS, Sutton, RE, Suryadevara, N, Chen, EC, Binshtein, E, Shrihari, S, Ostrowski, M, Chu, HY, Didier, JE, MacRenaris, KW, Jones, T, Day, S, Myers, L, Eun-Hyung Lee, F, Nguyen, DC, Sanz, I, Martinez, DR, Rothlauf, PW, Bloyet, LM, Whelan, SPJ, Baric, RS, Thackray, LB , Diamond, MS, Carnahan, RH & Crowe, JE 2020, 'Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein', Nature medicine, vol. 26, no. 9, pp. 1422-1427. https://doi.org/10.1038/s41591-020-0998-x

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T1 - Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein

AU - Zost, Seth J.

AU - Gilchuk, Pavlo

AU - Chen, Rita E.

AU - Case, James Brett

AU - Reidy, Joseph X.

AU - Trivette, Andrew

AU - Nargi, Rachel S.

AU - Sutton, Rachel E.

AU - Suryadevara, Naveenchandra

AU - Chen, Elaine C.

AU - Binshtein, Elad

AU - Shrihari, Swathi

AU - Ostrowski, Mario

AU - Chu, Helen Y.

AU - Didier, Jonathan E.

AU - MacRenaris, Keith W.

AU - Jones, Taylor

AU - Day, Samuel

AU - Myers, Luke

AU - Eun-Hyung Lee, F.

AU - Nguyen, Doan C.

AU - Sanz, Ignacio

AU - Martinez, David R.

AU - Rothlauf, Paul W.

AU - Bloyet, Louis Marie

AU - Whelan, Sean P.J.

AU - Baric, Ralph S.

AU - Thackray, Larissa B.

AU - Diamond, Michael S.

AU - Carnahan, Robert H.

AU - Crowe, James E.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - 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 date1,2. 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.

AB - 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 date1,2. 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.

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U2 - 10.1038/s41591-020-0998-x

DO - 10.1038/s41591-020-0998-x

M3 - Article

C2 - 32651581

AN - SCOPUS:85087684502

SN - 1078-8956

VL - 26

SP - 1422

EP - 1427

JO - Nature medicine

JF - Nature medicine

IS - 9

ER -

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

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