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Age differentially impacts adaptive immune responses induced by adenoviral versus mRNA vaccines against COVID-19

  • Beatrice Dallan,
  • Davide Proietto,
  • Martina De Laurentis,
  • Eleonora Gallerani,
  • Mara Martino,
  • Sara Ghisellini,
  • Amedeo Zurlo,
  • Stefano Volpato,
  • Benedetta Govoni,
  • Michela Borghesi,
  • Valentina Albanese,
  • Victor Appay,
  • Stefano Bonnini,
  • Sian Llewellyn-Lacey,
  • Salvatore Pacifico,
  • Laura Grumiro,
  • Martina Brandolini,
  • Simona Semprini,
  • Vittorio Sambri,
  • Kristin Ladell,
  • Helen M. Parry,
  • Paul A. H. Moss,
  • David A. Price,
  • Elena Barbieri,
  • Tatiana Bernardi,
  • Michela Boni,
  • Linda Dall’Olio,
  • Martina De Laurentis,
  • Caterina Fiorini,
  • Michele Fiorini,
  • Maurizio Govoni,
  • Margherita Neri,
  • Fabio Palma,
  • Franco Romagnoni,
  • Antonella Caputo,
  • Riccardo Gavioli,
  • Francesco Nicoli

摘要

Adenoviral and mRNA vaccines encoding the viral spike (S) protein have been deployed globally to contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Older individuals are particularly vulnerable to severe infection, probably reflecting age-related changes in the immune system, which can also compromise vaccine efficacy. It is nonetheless unclear to what extent different vaccine platforms are impacted by immunosenescence. Here, we evaluated S protein-specific immune responses elicited by vaccination with two doses of BNT162b2 or ChAdOx1-S and subsequently boosted with a single dose of BNT162b2 or mRNA-1273, comparing age-stratified participants with no evidence of previous infection with SARS-CoV-2. We found that aging profoundly compromised S protein-specific IgG titers and further limited S protein-specific CD4+ and CD8+ T cell immunity as a probable function of progressive erosion of the naive lymphocyte pool in individuals vaccinated initially with BNT162b2. Our results demonstrate that primary vaccination with ChAdOx1-S and subsequent boosting with BNT162b2 or mRNA-1273 promotes sustained immunological memory in older adults and potentially confers optimal protection against coronavirus disease 2019.