4.8 Article

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

Journal

CELL REPORTS
Volume 34, Issue 12, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2021.108890

Keywords

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Funding

  1. Medical Research Council [MR/R008698/1]
  2. AMC fellowship
  3. Vici grant from the Netherlands Organization for Scientific Research (NWO)
  4. MRC-KCL Doctoral Training Partnership in Biomedical Sciences [MR/N013700/1]
  5. UCL
  6. King's Together RapidKing's Together Rapid COVID-19 Call award
  7. Huo Family Foundation
  8. Royal Free Charity
  9. UK Coronavirus Immunology Consortium
  10. National Institutes of Health [P01 AI110657]
  11. Bill and Melinda Gates Foundation [INV-002022]
  12. Francis Crick Institute from Cancer Research UK [FC001061]
  13. UK Medical Research Council
  14. Wellcome Trust
  15. MRC UKRI [MC_PC_19082]
  16. UCLH/UCL NIHR BRC
  17. MRC [MC_PC_19082, MR/R008698/1] Funding Source: UKRI
  18. Bill and Melinda Gates Foundation [INV-002022] Funding Source: Bill and Melinda Gates Foundation

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The study found that emerging variants of the coronavirus may lead to reduced neutralization by antibodies induced by vaccines or previous infection, but some samples still retain effectiveness. This highlights the importance of real-time monitoring of emerging mutations and their impact on vaccine efficacy.
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 realtime monitoring of emerging mutations and their effect on vaccine efficacy.

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