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The effect of spike mutations on SARS-CoV-2 neutralization.
Cell Rep. 2021 03 23; 34(12):108890.CR

Abstract

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.

Authors+Show Affiliations

Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK.Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK.Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK.Advanced Pathogens Diagnostic Unit, Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London W1T 4EU, UK.Amsterdam University Medical Centers, Amsterdam Institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.Amsterdam University Medical Centers, Amsterdam Institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK.School of Immunology and Microbial Sciences, King's College London, London SE1 9RT, UK.School of Immunology and Microbial Sciences, King's College London, London SE1 9RT, UK.Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK.The Francis Crick Institute, London NW1 1AT, UK.The Francis Crick Institute, London NW1 1AT, UK.Advanced Pathogens Diagnostic Unit, Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London W1T 4EU, UK; Research Department of Infection, Division of Infection and Immunity, University College London, London WC1 6BT, UK.Amsterdam University Medical Centers, Amsterdam Institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.The Francis Crick Institute, London NW1 1AT, UK.Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK.Advanced Pathogens Diagnostic Unit, Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London W1T 4EU, UK; The Francis Crick Institute, London NW1 1AT, UK; Great Ormond Street Institute for Child Health, Infection, Immunity and Inflammation, University College London, London WC1N 1EH, UK.No affiliation info availableSchool of Immunology and Microbial Sciences, King's College London, London SE1 9RT, UK.Amsterdam University Medical Centers, Amsterdam Institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London NW3 2PF, UK. Electronic address: l.mccoy@ucl.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33713594

Citation

Rees-Spear, Chloe, et al. "The Effect of Spike Mutations On SARS-CoV-2 Neutralization." Cell Reports, vol. 34, no. 12, 2021, p. 108890.
Rees-Spear C, Muir L, Griffith SA, et al. The effect of spike mutations on SARS-CoV-2 neutralization. Cell Rep. 2021;34(12):108890.
Rees-Spear, C., Muir, L., Griffith, S. A., Heaney, J., Aldon, Y., Snitselaar, J. L., Thomas, P., Graham, C., Seow, J., Lee, N., Rosa, A., Roustan, C., Houlihan, C. F., Sanders, R. W., Gupta, R. K., Cherepanov, P., Stauss, H. J., Nastouli, E., Doores, K. J., ... McCoy, L. E. (2021). The effect of spike mutations on SARS-CoV-2 neutralization. Cell Reports, 34(12), 108890. https://doi.org/10.1016/j.celrep.2021.108890
Rees-Spear C, et al. The Effect of Spike Mutations On SARS-CoV-2 Neutralization. Cell Rep. 2021 03 23;34(12):108890. PubMed PMID: 33713594.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of spike mutations on SARS-CoV-2 neutralization. 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 - ,, AU - Doores,Katie J, AU - van Gils,Marit J, AU - McCoy,Laura E, Y1 - 2021/03/06/ PY - 2021/01/15/received PY - 2021/02/17/revised PY - 2021/03/01/accepted PY - 2021/3/14/pubmed PY - 2021/4/7/medline PY - 2021/3/13/entrez KW - B.1.1.7 KW - SARS-CoV-2 KW - antibodies KW - immune escape KW - neutralization KW - serology KW - variant SP - 108890 EP - 108890 JF - Cell reports JO - Cell Rep VL - 34 IS - 12 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. SN - 2211-1247 UR - https://www.unboundmedicine.com/medline/citation/33713594/The_effect_of_spike_mutations_on_SARS_CoV_2_neutralization_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(21)00204-7 DB - PRIME DP - Unbound Medicine ER -