Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity
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 w...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1056525/full |
| _version_ | 1797938686650744832 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Larissa Henze |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T19:04:41Z |
| format | Article |
| id | doaj.art-8d30110c924e4be5beac3a8eb0a4da1f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T19:04:41Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8d30110c924e4be5beac3a8eb0a4da1f2023-01-31T05:41:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.10565251056525Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunityLarissa Henze0Larissa Henze1Julian Braun2Julian Braun3Lil Meyer-Arndt4Lil Meyer-Arndt5Lil Meyer-Arndt6Lil Meyer-Arndt7Karsten Jürchott8Karsten Jürchott9Maike Schlotz10Janine Michel11Marica Grossegesse12Maike Mangold13Maike Mangold14Manuela Dingeldey15Manuela Dingeldey16Beate Kruse17Beate Kruse18Pavlo Holenya19Norbert Mages20Norbert Mages21Norbert Mages22Ulf Reimer23Maren Eckey24Karsten Schnatbaum25Holger Wenschuh26Bernd Timmermann27Florian Klein28Florian Klein29Florian Klein30Andreas Nitsche31Claudia Giesecke-Thiel32Lucie Loyal33Lucie Loyal34Andreas Thiel35Andreas Thiel36Si-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, GermanyRegenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, GermanySi-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, GermanyRegenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, GermanySi-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, GermanyRegenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, GermanyNeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Neurology with Experimental Neurology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanySi-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, GermanyRegenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, GermanyLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyHighly 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, GermanyHighly 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, GermanySi-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, GermanyRegenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, GermanySi-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, GermanyRegenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, GermanySi-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, GermanyRegenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, GermanyJPT Peptide Technologies GmbH, Berlin, GermanySi-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, GermanyRegenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, GermanyMax Planck Institute for Molecular Genetics, Berlin, GermanyJPT Peptide Technologies GmbH, Berlin, GermanyJPT Peptide Technologies GmbH, Berlin, GermanyJPT Peptide Technologies GmbH, Berlin, GermanyJPT Peptide Technologies GmbH, Berlin, GermanyMax Planck Institute for Molecular Genetics, Berlin, GermanyLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyGerman Center for Infection Research (DZIF), Partner site Bonn-Cologne, Cologne, Germany0Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, GermanyHighly 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, GermanyMax Planck Institute for Molecular Genetics, Berlin, GermanySi-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, GermanyRegenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, GermanySi-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, GermanyRegenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, GermanyCurrently 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1056525/fullSARS-CoV-2antigen-specific T-cellscross-reactivityheterologous vaccinationhumoral response |
| spellingShingle | 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 Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity Frontiers in Immunology SARS-CoV-2 antigen-specific T-cells cross-reactivity heterologous vaccination humoral response |
| title | Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity |
| title_full | Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity |
| title_fullStr | Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity |
| title_full_unstemmed | Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity |
| title_short | Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity |
| title_sort | primary chadox1 vaccination does not reactivate pre existing cross reactive immunity |
| topic | SARS-CoV-2 antigen-specific T-cells cross-reactivity heterologous vaccination humoral response |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1056525/full |
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