Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies
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...
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Published in | Nature medicine Vol. 27; no. 4; pp. 717 - 726 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.04.2021
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
A comprehensive analysis of antibody neutralization activity against a panel of authentic isolates and chimeric SARS-CoV-2 variants shows markedly diminished neutralizing activity against the variant B.1.351, first identified in South Africa. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 R.E.C. and J.B.C. performed and analyzed neutralization assays. D.P. carried out pseudovirus neutralization and flow cytometry assays. X.X., Y.L., J.L., and X.Z. designed and generated the isogenic SARS-CoV-2 variant viruses. S.T. L.D., and D.W. performed the deep sequencing analysis. A.H.E., R.M.P., J.A.O., A.K.J.K, and P.D. designed and supervised the clinical studies and J.S.T., W.K., M.T. and A.J.S. obtained and characterized clinical samples. A.C.M.B. provided hamster immune sera. D.C., N.S., P.G., S.J.Z., J.E.C., A.E., and H.W.V. provided mAbs and performed analysis. P.Y.S., A.H.E., D.C., and M.S.D. obtained funding and supervised the research. R.E.C, J.B.C., E.S.W., H.W.V., and M.S.D. wrote the initial draft, with the other authors providing editorial comments. AUTHOR CONTRIBUTIONS |
ISSN: | 1078-8956 1546-170X 1546-170X |
DOI: | 10.1038/s41591-021-01294-w |