SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies

Science. 2022 Feb 18;375(6582):782-787. doi: 10.1126/science.abm5835. Epub 2022 Jan 25.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. In this study, serum of Beta-infected patients revealed reduced cross-neutralization of wild-type virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wild type-elicited antibodies, including a public VH1-58 clonotype that targets the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift, with implications for design of next-generation vaccines and therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / genetics
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / genetics
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / metabolism
  • Antigenic Drift and Shift
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Cross Reactions*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neutralization Tests
  • Protein Binding
  • Protein Domains
  • Protein Interaction Domains and Motifs
  • SARS-CoV-2 / chemistry
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants