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

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

doi:10.3389/fimmu.2023.1056525

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

Front Immunol. 2023 Jan 31:14:1056525. doi: 10.3389/fimmu.2023.1056525. eCollection 2023.

Authors

Larissa Henze^{1

2}, Julian Braun^{1

2}, Lil Meyer-Arndt^{1

2

3

4}, Karsten Jürchott^{1

2}, Maike Schlotz⁵, Janine Michel⁶, Marica Grossegesse⁶, Maike Mangold^{1

2}, Manuela Dingeldey^{1

2}, Beate Kruse^{1

2}, Pavlo Holenya⁷, Norbert Mages^{1

2

8}, Ulf Reimer⁷, Maren Eckey⁷, Karsten Schnatbaum⁷, Holger Wenschuh⁷, Bernd Timmermann⁸, Florian Klein^{5

9

10}, Andreas Nitsche⁶, Claudia Giesecke-Thiel⁸, Lucie Loyal^{1

2}, Andreas Thiel^{1

2}

Affiliations

¹ Si-M/"Der Simulierte Mensch" a science framework of Technische Universität Berlin and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
² Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany.
³ NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁴ Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁵ Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
⁶ Highly Pathogenic Viruses, Centre for Biological Threats and Special Pathogens, WHO Reference Laboratory for SARS-CoV-2 and WHO Collaborating Centre for Emerging Infections and Biological Threats, Robert Koch Institute, Berlin, Germany.
⁷ JPT Peptide Technologies GmbH, Berlin, Germany.
⁸ Max Planck Institute for Molecular Genetics, Berlin, Germany.
⁹ German Center for Infection Research (DZIF), Partner site Bonn-Cologne, Cologne, Germany.
¹⁰ Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

Abstract

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.

Keywords: SARS-CoV-2; antigen-specific T-cells; cross-reactivity; heterologous vaccination; humoral response.

Copyright © 2023 Henze, Braun, Meyer-Arndt, Jürchott, Schlotz, Michel, Grossegesse, Mangold, Dingeldey, Kruse, Holenya, Mages, Reimer, Eckey, Schnatbaum, Wenschuh, Timmermann, Klein, Nitsche, Giesecke-Thiel, Loyal and Thiel.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

BNT162 Vaccine* / immunology
COVID-19* / prevention & control
ChAdOx1 nCoV-19* / immunology
Cross Reactions*
Humans
Receptors, Antigen, T-Cell
SARS-CoV-2
Vaccination

Substances

BNT162 Vaccine
ChAdOx1 nCoV-19
Receptors, Antigen, T-Cell

Grants and funding

This work was funded by the Federal Ministry of Health through a resolution of the German Bundestag (Charité Corona Cross (CCC) 2.0 and 2.1 and Charité Corona Protect (CCP)).