Cross-reactive antibodies after SARS-CoV-2 infection and vaccination

Elife. 2021 Nov 23:10:e70330. doi: 10.7554/eLife.70330.

Abstract

Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11- to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2- to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 vaccination in macaques and humans, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.

Keywords: COVID-19; SARS-CoV-2; antibodies; coronavirus; cross-reactivity; human; immunology; infectious disease; inflammation; microbiology; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • COVID-19 Vaccines / immunology*
  • Coronavirus / immunology
  • Cross Reactions / immunology
  • Healthy Volunteers
  • Humans
  • Immunoglobulin G / immunology
  • Macaca
  • Middle East Respiratory Syndrome Coronavirus / immunology
  • Principal Component Analysis
  • Protein Domains / immunology
  • SARS-CoV-2 / immunology*
  • Serum / immunology
  • Serum / virology
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Tetanus Toxoid / immunology
  • mRNA Vaccines / immunology

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • Tetanus Toxoid
  • mRNA Vaccines
  • spike glycoprotein, SARS-CoV

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.