The effect of spike mutations on SARS-CoV-2 neutralization

TY - JOUR

T1 - The effect of spike mutations on SARS-CoV-2 neutralization

AU - SAFER Investigators

AU - Rees-Spear, Chloe

AU - Muir, Luke

AU - Griffith, Sarah A

AU - Heaney, Judith

AU - Aldon, Yoann

AU - Snitselaar, Jonne L

AU - Thomas, Peter

AU - Graham, Carl

AU - Seow, Jeffrey

AU - Lee, Nayung

AU - Rosa, Annachiara

AU - Roustan, Chloe

AU - Houlihan, Catherine F

AU - Sanders, Rogier W

AU - Gupta, Ravindra K

AU - Cherepanov, Peter

AU - Stauss, Hans J

AU - Nastouli, Eleni

AU - Doores, Katie J

AU - van Gils, Marit J

AU - McCoy, Laura E

N1 - Funding Information: The authors would like to thank James E. Voss for the gift of HeLa ACE2-expressing cells and George Kassiotis, Dan Frampton, Ann-Kathrin Reuschl, and Joe Grove for critical feedback. We are indebted to the Biobank staff and study participants and their families at the Royal Free Hospital and the UCLH SAFER study recruitment team and study participants. L.E.M. is supported by a Medical Research Council career development award (MR/R008698/1). M.J.v.G. is a recipient of an AMC fellowship, and R.W.S. is a recipient of a Vici grant from the Netherlands Organization for Scientific Research (NWO). C.G. is supported by the MRC-KCL Doctoral Training Partnership in Biomedical Sciences (MR/N013700/1). This study was also funded by the UCL Coronavirus Response Fund, made possible through generous donations from UCL's supporters, alumni, and friends (to L.E.M.); the King's Together Rapid COVID-19 Call award (to K.J.D.); the Huo Family Foundation (to K.J.D.); the Royal Free Charity; and the UK Coronavirus Immunology Consortium. This work was also supported by National Institutes of Health grant P01 AI110657 and Bill and Melinda Gates Foundation grant INV-002022 (to R.W.S.). The work in laboratory of P.C. was supported by the Francis Crick Institute (FC001061), which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust. The SAFER study was funded by MRC UKRI (MC_PC_19082) and supported by the UCLH/UCL NIHR BRC. K.J.D. L.E.M. L.M. S.A.G. P.T. N.L. and C.R.-S. characterized monoclonal antibodies and sera. A.R. C.R. and P.C. expressed and purified proteins. J.H. C.F.H. H.J.S. and E.N. assembled the panels of human serum samples. M.J.v.G. R.W.S. Y.A. and J.L.S. isolated and provided monoclonal antibodies. R.K.G. generated and provided mutated spike plasmids. M.J.v.G. K.J.D. and L.E.M. wrote the paper with contributions from all authors. Amsterdam UMC submitted a patent application on SARS-CoV-2 monoclonal antibodies, some of which were used in this study. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/3/23

Y1 - 2021/3/23

N2 - Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines show protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, spike. Because new SARS-CoV-2 variants are emerging rapidly, as exemplified by the B.1.1.7, B.1.351, and P.1 lineages, it is critical to understand whether antibody responses induced by infection with the original SARS-CoV-2 virus or current vaccines remain effective. In this study, we evaluate neutralization of a series of mutated spike pseudotypes based on divergence from SARS-CoV and then compare neutralization of the B.1.1.7 spike pseudotype and individual mutations. Spike-specific monoclonal antibody neutralization is reduced dramatically; in contrast, polyclonal antibodies from individuals infected in early 2020 remain active against most mutated spike pseudotypes, but potency is reduced in a minority of samples. This work highlights that changes in SARS-CoV-2 spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their effect on vaccine efficacy.

AB - Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines show protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, spike. Because new SARS-CoV-2 variants are emerging rapidly, as exemplified by the B.1.1.7, B.1.351, and P.1 lineages, it is critical to understand whether antibody responses induced by infection with the original SARS-CoV-2 virus or current vaccines remain effective. In this study, we evaluate neutralization of a series of mutated spike pseudotypes based on divergence from SARS-CoV and then compare neutralization of the B.1.1.7 spike pseudotype and individual mutations. Spike-specific monoclonal antibody neutralization is reduced dramatically; in contrast, polyclonal antibodies from individuals infected in early 2020 remain active against most mutated spike pseudotypes, but potency is reduced in a minority of samples. This work highlights that changes in SARS-CoV-2 spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their effect on vaccine efficacy.

UR - http://www.scopus.com/inward/record.url?scp=85102441962&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.108890

DO - 10.1016/j.celrep.2021.108890

M3 - Article

C2 - 33713594

SN - 2211-1247

VL - 34

SP - 108890

JO - Cell Reports

JF - Cell Reports

IS - 12

M1 - 108890

ER -