Frontiers in Immunology (Jan 2023)

Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity

  • Larissa Henze,
  • Larissa Henze,
  • Julian Braun,
  • Julian Braun,
  • Lil Meyer-Arndt,
  • Lil Meyer-Arndt,
  • Lil Meyer-Arndt,
  • Lil Meyer-Arndt,
  • Karsten Jürchott,
  • Karsten Jürchott,
  • Maike Schlotz,
  • Janine Michel,
  • Marica Grossegesse,
  • Maike Mangold,
  • Maike Mangold,
  • Manuela Dingeldey,
  • Manuela Dingeldey,
  • Beate Kruse,
  • Beate Kruse,
  • Pavlo Holenya,
  • Norbert Mages,
  • Norbert Mages,
  • Norbert Mages,
  • Ulf Reimer,
  • Maren Eckey,
  • Karsten Schnatbaum,
  • Holger Wenschuh,
  • Bernd Timmermann,
  • Florian Klein,
  • Florian Klein,
  • Florian Klein,
  • Andreas Nitsche,
  • Claudia Giesecke-Thiel,
  • Lucie Loyal,
  • Lucie Loyal,
  • Andreas Thiel,
  • Andreas Thiel

DOI
https://doi.org/10.3389/fimmu.2023.1056525
Journal volume & issue
Vol. 14

Abstract

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Currently available COVID-19 vaccines include inactivated virus, live attenuated virus, mRNA-based, viral vectored and adjuvanted protein-subunit-based vaccines. All of them contain the spike glycoprotein as the main immunogen and result in reduced disease severity upon SARS-CoV-2 infection. While we and others have shown that mRNA-based vaccination reactivates pre-existing, cross-reactive immunity, the effect of vector vaccines in this regard is unknown. Here, we studied cellular and humoral responses in heterologous adenovirus-vector-based ChAdOx1 nCOV-19 (AZ; Vaxzeria, AstraZeneca) and mRNA-based BNT162b2 (BNT; Comirnaty, BioNTech/Pfizer) vaccination and compared it to a homologous BNT vaccination regimen. AZ primary vaccination did not lead to measurable reactivation of cross-reactive cellular and humoral immunity compared to BNT primary vaccination. Moreover, humoral immunity induced by primary vaccination with AZ displayed differences in linear spike peptide epitope coverage and a lack of anti-S2 IgG antibodies. Contrary to primary AZ vaccination, secondary vaccination with BNT reactivated pre-existing, cross-reactive immunity, comparable to homologous primary and secondary mRNA vaccination. While induced anti-S1 IgG antibody titers were higher after heterologous vaccination, induced CD4+ T cell responses were highest in homologous vaccinated. However, the overall TCR repertoire breadth was comparable between heterologous AZ-BNT-vaccinated and homologous BNT-BNT-vaccinated individuals, matching TCR repertoire breadths after SARS-CoV-2 infection, too. The reasons why AZ and BNT primary vaccination elicits different immune response patterns to essentially the same antigen, and the associated benefits and risks, need further investigation to inform vaccine and vaccination schedule development.

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