Frontiers in Immunology (Dec 2023)

Contribution of SARS-CoV-2 infection preceding COVID-19 mRNA vaccination to generation of cellular and humoral immune responses in children

  • Marije K. Verheul,
  • Martijn Vos,
  • Lia de Rond,
  • Mary-Lène De Zeeuw-Brouwer,
  • Kim H. Nijhof,
  • Debbie Smit,
  • Debbie Oomen,
  • Petra Molenaar,
  • Marjan Bogaard,
  • Rianne van Bergen,
  • Irene Middelhof,
  • Lisa Beckers,
  • Alienke J. Wijmenga-Monsuur,
  • Anne-Marie Buisman,
  • Mardi C. Boer,
  • Rob van Binnendijk,
  • Jelle de Wit,
  • Teun Guichelaar

DOI
https://doi.org/10.3389/fimmu.2023.1327875
Journal volume & issue
Vol. 14

Abstract

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Primary COVID-19 vaccination for children, 5-17 years of age, was offered in the Netherlands at a time when a substantial part of this population had already experienced a SARS-CoV-2 infection. While vaccination has been shown effective, underlying immune responses have not been extensively studied. We studied immune responsiveness to one and/or two doses of primary BNT162b2 mRNA vaccination and compared the humoral and cellular immune response in children with and without a preceding infection. Antibodies targeting the original SARS-CoV-2 Spike or Omicron Spike were measured by multiplex immunoassay. B-cell and T-cell responses were investigated using enzyme-linked immunosorbent spot (ELISpot) assays. The activation of CD4+ and CD8+ T cells was studied by flowcytometry. Primary vaccination induced both a humoral and cellular adaptive response in naive children. These responses were stronger in those with a history of infection prior to vaccination. A second vaccine dose did not further boost antibody levels in those who previously experienced an infection. Infection-induced responsiveness prior to vaccination was mainly detected in CD8+ T cells, while vaccine-induced T-cell responses were mostly by CD4+ T cells. Thus, SARS-CoV-2 infection prior to vaccination enhances adaptive cellular and humoral immune responses to primary COVID-19 vaccination in children. As most children are now expected to contract infection before the age of five, the impact of infection-induced immunity in children is of high relevance. Therefore, considering natural infection as a priming immunogen that enhances subsequent vaccine-responsiveness may help decision-making on the number and timing of vaccine doses.

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