Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2

EBioMedicine. 2021 Dec:74:103700. doi: 10.1016/j.ebiom.2021.103700. Epub 2021 Nov 30.

Abstract

Background: Antibodies raised against human seasonal coronaviruses (sCoVs), which are responsible for the common cold, are known to cross-react with SARS-CoV-2 antigens. This prompts questions about their protective role against SARS-CoV-2 infections and COVID-19 severity. However, the relationship between sCoVs exposure and SARS-CoV-2 correlates of protection are not clearly identified.

Methods: We performed a cross-sectional analysis of cross-reactivity and cross-neutralization to SARS-CoV-2 antigens (S-RBD, S-trimer, N) using pre-pandemic sera from four different groups: pediatrics and adolescents, individuals 21 to 70 years of age, older than 70 years of age, and individuals living with HCV or HIV. Data was then further analysed using machine learning to identify predictive patterns of neutralization based on sCoVs serology.

Findings: Antibody cross-reactivity to SARS-CoV-2 antigens varied between 1.6% and 15.3% depending on the cohort and the isotype-antigen pair analyzed. We also show a range of neutralizing activity (0-45%) with median inhibition ranging from 17.6 % to 23.3 % in serum that interferes with SARS-CoV-2 spike attachment to ACE2 independently of age group. While the abundance of sCoV antibodies did not directly correlate with neutralization, we show that neutralizing activity is rather dependent on relative ratios of IgGs in sera directed to all four sCoV spike proteins. More specifically, we identified antibodies to NL63 and OC43 as being the most important predictors of neutralization.

Interpretation: Our data support the concept that exposure to sCoVs triggers antibody responses that influence the efficiency of SARS-CoV-2 spike binding to ACE2, which may potentially impact COVID-19 disease severity through other latent variables.

Funding: This study was supported by a grant by the CIHR (VR2 -172722) and by a grant supplement by the CITF, and by a NRC Collaborative R&D Initiative Grant (PR031-1).

Keywords: 229E; COVID-19; HKU1; NL63; OC43; SARS-CoV-2; human coronaviruses; pre-existing immunity; seasonal coronavirus.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood*
  • COVID-19 / immunology
  • COVID-19 / pathology
  • Common Cold / virology
  • Coronavirus 229E, Human / immunology*
  • Coronavirus NL63, Human / immunology*
  • Coronavirus OC43, Human / immunology*
  • Cross Reactions / immunology
  • Cross-Sectional Studies
  • Humans
  • Middle Aged
  • SARS-CoV-2 / immunology*
  • Seroepidemiologic Studies
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2