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
Affiliations
- Larissa Henze
- 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
- Larissa Henze
- Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany
- Julian Braun
- 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
- Julian Braun
- Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany
- Lil Meyer-Arndt
- 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
- Lil Meyer-Arndt
- Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany
- Lil Meyer-Arndt
- NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
- Lil Meyer-Arndt
- 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
- Karsten Jürchott
- 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
- Karsten Jürchott
- Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany
- Maike Schlotz
- Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Janine Michel
- 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
- Marica Grossegesse
- 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
- Maike Mangold
- 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
- Maike Mangold
- Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany
- Manuela Dingeldey
- 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
- Manuela Dingeldey
- Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany
- Beate Kruse
- 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
- Beate Kruse
- Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany
- Pavlo Holenya
- JPT Peptide Technologies GmbH, Berlin, Germany
- Norbert Mages
- 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
- Norbert Mages
- Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany
- Norbert Mages
- Max Planck Institute for Molecular Genetics, Berlin, Germany
- Ulf Reimer
- JPT Peptide Technologies GmbH, Berlin, Germany
- Maren Eckey
- JPT Peptide Technologies GmbH, Berlin, Germany
- Karsten Schnatbaum
- JPT Peptide Technologies GmbH, Berlin, Germany
- Holger Wenschuh
- JPT Peptide Technologies GmbH, Berlin, Germany
- Bernd Timmermann
- Max Planck Institute for Molecular Genetics, Berlin, Germany
- Florian Klein
- Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Florian Klein
- German Center for Infection Research (DZIF), Partner site Bonn-Cologne, Cologne, Germany
- Florian Klein
- 0Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
- Andreas Nitsche
- 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
- Claudia Giesecke-Thiel
- Max Planck Institute for Molecular Genetics, Berlin, Germany
- Lucie Loyal
- 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
- Lucie Loyal
- Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany
- Andreas Thiel
- 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
- Andreas Thiel
- Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany
- DOI
- https://doi.org/10.3389/fimmu.2023.1056525
- Journal volume & issue
-
Vol. 14
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