학술논문
Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2.
Document Type
Academic Journal
Author
Vogel E; Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.; Kocher K; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Wasserturmstr. 3/5, 91054 Erlangen, Germany.; Priller A; Institute of Molecular Immunology and Experimental Oncology, School of Medicine, University Hospital rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 München, Germany.; Cheng CC; Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.; Steininger P; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany.; Liao BH; Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.; Körber N; Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.; Willmann A; Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.; Irrgang P; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany.; Held J; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Wasserturmstr. 3/5, 91054 Erlangen, Germany.; Moosmann C; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Wasserturmstr. 3/5, 91054 Erlangen, Germany.; Schmidt V; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Wasserturmstr. 3/5, 91054 Erlangen, Germany.; Beileke S; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany.; Wytopil M; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany.; Heringer S; University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany.; Bauer T; Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.; Brockhoff R; University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany.; Jeske S; Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.; Mijocevic H; Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.; Christa C; Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.; Salmanton-García J; University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany.; Tinnefeld K; Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.; Bogdan C; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Wasserturmstr. 3/5, 91054 Erlangen, Germany.; Yazici S; Institute of Molecular Immunology and Experimental Oncology, School of Medicine, University Hospital rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 München, Germany.; Knolle P; Institute of Molecular Immunology and Experimental Oncology, School of Medicine, University Hospital rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 München, Germany; German Center for Infection Research (DZIF), partner sites Munich and Cologne.; Cornely OA; University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany; German Center for Infection Research (DZIF), partner sites Munich and Cologne; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Kerpener Str. 62, 50937 Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS Köln), Cologne, Germany.; Überla K; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany.; Protzer U; Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany; German Center for Infection Research (DZIF), partner sites Munich and Cologne. Electronic address: protzer@tum.de.; Schober K; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Wasserturmstr. 3/5, 91054 Erlangen, Germany. Electronic address: kilian.schober@uk-erlangen.de.; Tenbusch M; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany. Electronic address: matthias.tenbusch@fau.de.
Source
Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101647039 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-3964 (Electronic) Linking ISSN: 23523964 NLM ISO Abbreviation: EBioMedicine Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Vaccines are an important means to overcome the SARS-CoV-2 pandemic. They induce specific antibody and T-cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 180 days after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both.
Methods: Various tests were used to determine the humoral and cellular immune response. To quantify the antibody levels, we used the surrogate neutralization (sVNT) assay from YHLO, which we augmented with pseudo- and real virus neutralization tests (pVNT and rVNT). Antibody avidity was measured by a modified ELISA. To determine cellular reactivity, we used an IFN-γ Elispot, IFN-γ/IL Flurospot, and intracellular cytokine staining.
Findings: Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize SARS-CoV-2 - including variants of concern such as Delta or Omicron - was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homologous ChAd immunization. All vaccination regimens induced stable, polyfunctional T-cell responses.
Interpretation: These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent alternative to induce humoral and cellular immune protection in comparison to the homologous vaccination regimens.
Funding: The study was funded by the German Centre for Infection Research (DZIF), the European Union's "Horizon 2020 Research and Innovation Programme" under grant agreement No. 101037867 (VACCELERATE), the "Bayerisches Staatsministerium für Wissenschaft und Kunst" for the CoVaKo-2021 and the For-COVID projects and the Helmholtz Association via the collaborative research program "CoViPa". Further support was obtained from the Federal Ministry of Education and Science (BMBF) through the "Netzwerk Universitätsmedizin", project "B-Fast" and "Cov-Immune". KS is supported by the German Federal Ministry of Education and Research (BMBF, 01KI2013) and the Else Kröner-Stiftung (2020_EKEA.127).
Competing Interests: Declaration of interests J.H. reports grants and speaker honoraria from Pfizer, outside the study. JSG received speaker honoraria from Gilead Nordica and Pfizer Ireland, outside the study. P.K. reports to serve as scientific adviser to Avexis and Freeline and a grant from Roche outside from this study. U.P. reports grants from ALiOS and VirBio, and personal fees from AbbVie, Arbutus, Gilead, GSK, Johnson & Johnson, Roche, Sobi, and Vaccitech, outside the study. U.P. is co-founder and shareholder of SCG Cell Therapy O.A.C. reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Pfizer; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Jannsen, MedPace, Paratek, PSI, Shionogi; A patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Other interests from DGHO, DGI, ECMM, ISHAM, MSG-ERC, Wiley, outside the submitted work. All other authors declare no competing interests.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Methods: Various tests were used to determine the humoral and cellular immune response. To quantify the antibody levels, we used the surrogate neutralization (sVNT) assay from YHLO, which we augmented with pseudo- and real virus neutralization tests (pVNT and rVNT). Antibody avidity was measured by a modified ELISA. To determine cellular reactivity, we used an IFN-γ Elispot, IFN-γ/IL Flurospot, and intracellular cytokine staining.
Findings: Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize SARS-CoV-2 - including variants of concern such as Delta or Omicron - was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homologous ChAd immunization. All vaccination regimens induced stable, polyfunctional T-cell responses.
Interpretation: These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent alternative to induce humoral and cellular immune protection in comparison to the homologous vaccination regimens.
Funding: The study was funded by the German Centre for Infection Research (DZIF), the European Union's "Horizon 2020 Research and Innovation Programme" under grant agreement No. 101037867 (VACCELERATE), the "Bayerisches Staatsministerium für Wissenschaft und Kunst" for the CoVaKo-2021 and the For-COVID projects and the Helmholtz Association via the collaborative research program "CoViPa". Further support was obtained from the Federal Ministry of Education and Science (BMBF) through the "Netzwerk Universitätsmedizin", project "B-Fast" and "Cov-Immune". KS is supported by the German Federal Ministry of Education and Research (BMBF, 01KI2013) and the Else Kröner-Stiftung (2020_EKEA.127).
Competing Interests: Declaration of interests J.H. reports grants and speaker honoraria from Pfizer, outside the study. JSG received speaker honoraria from Gilead Nordica and Pfizer Ireland, outside the study. P.K. reports to serve as scientific adviser to Avexis and Freeline and a grant from Roche outside from this study. U.P. reports grants from ALiOS and VirBio, and personal fees from AbbVie, Arbutus, Gilead, GSK, Johnson & Johnson, Roche, Sobi, and Vaccitech, outside the study. U.P. is co-founder and shareholder of SCG Cell Therapy O.A.C. reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Pfizer; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Jannsen, MedPace, Paratek, PSI, Shionogi; A patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Other interests from DGHO, DGI, ECMM, ISHAM, MSG-ERC, Wiley, outside the submitted work. All other authors declare no competing interests.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)