SARS-CoV-2 variants, spike mutations and immune escape

Harvey, W. T. et al. (2021) SARS-CoV-2 variants, spike mutations and immune escape. Nature Reviews Microbiology, 19(7), pp. 409-424. (doi: 10.1038/s41579-021-00573-0) (PMID:34075212) (PMCID:PMC8167834)

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Abstract

Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

Item Type:Articles
Additional Information:The COVID-19 Genomics UK (COG-UK) Consortium is supported by funding from the UK Medical Research Council (MRC), part of UK Research and Innovation, the UK National Institute of Health Research and Genome Research Limited, operating as the Wellcome Sanger Institute. W.T.H. is funded by the MRC (MR/R024758/1). R.R. is funded by the UK Biotechnology and Biological Sciences Research Council (BB/R012679/1). D.L.R. and E.C.T. are funded by the MRC (MC_UU_12014/12) and acknowledge the support of the G2P-UK National Virology Consortium (MR/W005611/1) funded by UK Research and Innovation. D.LR. also acknowledges support of the Wellcome Trust (220977/Z/20/Z). A.R. acknowledges the support of the Wellcome Trust (Collaborators Award 206298/Z/17/Z — ARTIC network) and the European Research Council (grant agreement no. 725422 — ReservoirDOCS).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Thomson, Professor Emma and Robertson, Professor David and Reeve, Professor Richard and Harvey, Dr William
Authors: Harvey, W. T., Carabelli, A. M., Jackson, B., Gupta, R. K., Thomson, E. C., Harrison, E. M., Ludden, C., Reeve, R., Rambaut, A., COVID-19 Genomics UK (COG-UK) Consortium, ., Peacock, S. J., and Robertson, D. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Reviews Microbiology
Publisher:Nature Research
ISSN:1740-1526
ISSN (Online):1740-1534
Published Online:01 June 2021
Copyright Holders:Copyright © 2021 Springer Nature Limited
First Published:First published in Nature Reviews Microbiology 19(7): 409-424
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
302632Using a comparative One Health approach to investigate the structural basis of antigenic variation among human and avian influenza virusesJill PellMedical Research Council (MRC)MR/R024758/1Institute of Biodiversity, Animal Health and Comparative Medicine
Viral Genomics and BioinformaticsAndrew DavisonMedical Research Council (MRC)MC_UU_12014/12III-MRC-GU Centre for Virus Research