Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection

Nat Immunol. 2022 Jan;23(1):40-49. doi: 10.1038/s41590-021-01089-8. Epub 2021 Dec 22.

Abstract

SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3-11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology
  • Adult
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • COVID-19 / immunology
  • COVID-19 Vaccines / immunology
  • Child
  • Child, Preschool
  • Coronavirus 229E, Human / immunology*
  • Coronavirus OC43, Human / immunology*
  • Cross Protection / immunology*
  • Cross Reactions / immunology
  • Humans
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology*

Substances

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

Supplementary concepts

  • SARS-CoV-2 variants