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

Cell Rep. 2021 Mar 23;34(12):108890. doi: 10.1016/j.celrep.2021.108890. Epub 2021 Mar 6.

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.

Keywords: B.1.1.7; SARS-CoV-2; antibodies; immune escape; neutralization; serology; variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology
  • Antibody Formation
  • COVID-19 / immunology
  • COVID-19 / metabolism
  • COVID-19 / virology*
  • COVID-19 Vaccines / immunology
  • HEK293 Cells
  • Humans
  • Neutralization Tests / methods
  • Point Mutation
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants