Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies

Rita E. Chen; Xianwen Zhang; James Brett Case; Emma S. Winkler; Yang Liu; Laura A. VanBlargan; Jianying Liu; John M. Errico; Xuping Xie; Naveenchandra Suryadevara; Pavlo Gilchuk; Seth J. Zost; Stephen Tahan; Lindsay Droit; Jackson S. Turner; Wooseob Kim; Aaron J. Schmitz; Mahima Thapa; David Wang; Adrianus C.M. Boon; Rachel M. Presti; Jane A. O’Halloran; Alfred H.J. Kim; Parakkal Deepak; Dora Pinto; Daved H. Fremont; James E. Crowe; Davide Corti; Herbert W. Virgin; Ali H. Ellebedy; Pei Yong Shi; Michael S. Diamond

doi:10.1038/s41591-021-01294-w

Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies

Rita E. Chen, Xianwen Zhang, James Brett Case, Emma S. Winkler, Yang Liu, Laura A. VanBlargan, Jianying Liu, John M. Errico, Xuping Xie, Naveenchandra Suryadevara, Pavlo Gilchuk, Seth J. Zost, Stephen Tahan, Lindsay Droit, Jackson S. Turner, Wooseob Kim, Aaron J. Schmitz, Mahima Thapa, David Wang, Adrianus C.M. BoonRachel M. Presti, Jane A. O’Halloran, Alfred H.J. Kim, Parakkal Deepak, Dora Pinto, Daved H. Fremont, James E. Crowe, Davide Corti, Herbert W. Virgin, Ali H. Ellebedy, Pei Yong Shi, Michael S. Diamond

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650 Scopus citations

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.

Original language	English
Pages (from-to)	717-726
Number of pages	10
Journal	Nature medicine
Volume	27
Issue number	4
DOIs	https://doi.org/10.1038/s41591-021-01294-w
State	Published - Apr 2021

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Chen, R. E., Zhang, X., Case, J. B., Winkler, E. S., Liu, Y., VanBlargan, L. A., Liu, J., Errico, J. M., Xie, X., Suryadevara, N., Gilchuk, P., Zost, S. J., Tahan, S., Droit, L., Turner, J. S., Kim, W., Schmitz, A. J., Thapa, M., Wang, D., ... Diamond, M. S. (2021). Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nature medicine, 27(4), 717-726. https://doi.org/10.1038/s41591-021-01294-w

@article{c6624b1ba1e247a684fc5cd1b6450865,

title = "Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies",

abstract = "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.",

author = "Chen, {Rita E.} and Xianwen Zhang and Case, {James Brett} and Winkler, {Emma S.} and Yang Liu and VanBlargan, {Laura A.} and Jianying Liu and Errico, {John M.} and Xuping Xie and Naveenchandra Suryadevara and Pavlo Gilchuk and Zost, {Seth J.} and Stephen Tahan and Lindsay Droit and Turner, {Jackson S.} and Wooseob Kim and Schmitz, {Aaron J.} and Mahima Thapa and David Wang and Boon, {Adrianus C.M.} and Presti, {Rachel M.} and O{\textquoteright}Halloran, {Jane A.} and Kim, {Alfred H.J.} and Parakkal Deepak and Dora Pinto and Fremont, {Daved H.} and Crowe, {James E.} and Davide Corti and Virgin, {Herbert W.} and Ellebedy, {Ali H.} and Shi, {Pei Yong} and Diamond, {Michael S.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.",

year = "2021",

month = apr,

doi = "10.1038/s41591-021-01294-w",

language = "English",

volume = "27",

pages = "717--726",

journal = "Nature medicine",

issn = "1078-8956",

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Chen, RE, Zhang, X, Case, JB, Winkler, ES, Liu, Y, VanBlargan, LA, Liu, J, Errico, JM, Xie, X, Suryadevara, N, Gilchuk, P, Zost, SJ, Tahan, S, Droit, L, Turner, JS, Kim, W, Schmitz, AJ, Thapa, M, Wang, D , Boon, ACM , Presti, RM, O’Halloran, JA, Kim, AHJ , Deepak, P, Pinto, D, Fremont, DH, Crowe, JE, Corti, D, Virgin, HW, Ellebedy, AH, Shi, PY & Diamond, MS 2021, 'Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies', Nature medicine, vol. 27, no. 4, pp. 717-726. https://doi.org/10.1038/s41591-021-01294-w

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AU - Chen, Rita E.

AU - Zhang, Xianwen

AU - Case, James Brett

AU - Winkler, Emma S.

AU - Liu, Yang

AU - VanBlargan, Laura A.

AU - Liu, Jianying

AU - Errico, John M.

AU - Xie, Xuping

AU - Suryadevara, Naveenchandra

AU - Gilchuk, Pavlo

AU - Zost, Seth J.

AU - Tahan, Stephen

AU - Droit, Lindsay

AU - Turner, Jackson S.

AU - Kim, Wooseob

AU - Schmitz, Aaron J.

AU - Thapa, Mahima

AU - Wang, David

AU - Boon, Adrianus C.M.

AU - Presti, Rachel M.

AU - O’Halloran, Jane A.

AU - Kim, Alfred H.J.

AU - Deepak, Parakkal

AU - Pinto, Dora

AU - Fremont, Daved H.

AU - Crowe, James E.

AU - Corti, Davide

AU - Virgin, Herbert W.

AU - Ellebedy, Ali H.

AU - Shi, Pei Yong

AU - Diamond, Michael S.

PY - 2021/4

Y1 - 2021/4

N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.

AB - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.

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DO - 10.1038/s41591-021-01294-w

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ER -

Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies

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