Pre-existing humoral immunity to human common cold coronaviruses negatively impacts the protective SARS-CoV-2 antibody response

Cell Host Microbe. 2022 Jan 12;30(1):83-96.e4. doi: 10.1016/j.chom.2021.12.005. Epub 2021 Dec 7.

Abstract

SARS-CoV-2 infection causes diverse outcomes ranging from asymptomatic infection to respiratory distress and death. A major unresolved question is whether prior immunity to endemic, human common cold coronaviruses (hCCCoVs) impacts susceptibility to SARS-CoV-2 infection or immunity following infection and vaccination. Therefore, we analyzed samples from the same individuals before and after SARS-CoV-2 infection or vaccination. We found hCCCoV antibody levels increase after SARS-CoV-2 exposure, demonstrating cross-reactivity. However, a case-control study indicates that baseline hCCCoV antibody levels are not associated with protection against SARS-CoV-2 infection. Rather, higher magnitudes of pre-existing betacoronavirus antibodies correlate with more SARS-CoV-2 antibodies following infection, an indicator of greater disease severity. Additionally, immunization with hCCCoV spike proteins before SARS-CoV-2 immunization impedes the generation of SARS-CoV-2-neutralizing antibodies in mice. Together, these data suggest that pre-existing hCCCoV antibodies hinder SARS-CoV-2 antibody-based immunity following infection and provide insight on how pre-existing coronavirus immunity impacts SARS-CoV-2 infection, which is critical considering emerging variants.

Keywords: 229E; COVID-19; HKU1; NL63; OC43; SARS-CoV-2; antibody; pre-existing immunity.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Antibody Formation / immunology*
  • Asymptomatic Infections
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Case-Control Studies
  • Cell Line
  • Common Cold / immunology*
  • Common Cold / virology
  • Cross Reactions / immunology
  • Female
  • HEK293 Cells
  • Humans
  • Immunity, Humoral / immunology*
  • Mice
  • Mice, Inbred C57BL
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus