Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2
Emanuel Vogel,
Katharina Kocher,
Alina Priller,
Cho-Chin Cheng,
Philipp Steininger,
Bo-Hung Liao,
Nina Körber,
Annika Willmann,
Pascal Irrgang,
Jürgen Held,
Carolin Moosmann,
Viviane Schmidt,
Stephanie Beileke,
Monika Wytopil,
Sarah Heringer,
Tanja Bauer,
Ronja Brockhoff,
Samuel Jeske,
Hrvoje Mijocevic,
Catharina Christa,
Jon Salmanton-García,
Kathrin Tinnefeld,
Christian Bogdan,
Sarah Yazici,
Percy Knolle,
Oliver A. Cornely,
Klaus Überla,
Ulrike Protzer,
Kilian Schober,
Matthias Tenbusch
Affiliations
Emanuel Vogel
Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany
Katharina Kocher
Mikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Wasserturmstr. 3/5, 91054 Erlangen, Germany
Alina Priller
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
Cho-Chin Cheng
Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany
Philipp Steininger
Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany
Bo-Hung Liao
Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany
Nina Körber
Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany
Annika Willmann
Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany
Pascal Irrgang
Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany
Jürgen Held
Mikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Wasserturmstr. 3/5, 91054 Erlangen, Germany
Carolin Moosmann
Mikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Wasserturmstr. 3/5, 91054 Erlangen, Germany
Viviane Schmidt
Mikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Wasserturmstr. 3/5, 91054 Erlangen, Germany
Stephanie Beileke
Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany
Monika Wytopil
Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany
Sarah Heringer
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
Tanja Bauer
Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany
Ronja Brockhoff
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
Samuel Jeske
Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany
Hrvoje Mijocevic
Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany
Catharina Christa
Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany
Jon Salmanton-García
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
Kathrin Tinnefeld
Institute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany
Christian Bogdan
Mikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Wasserturmstr. 3/5, 91054 Erlangen, Germany
Sarah Yazici
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
Percy Knolle
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
Oliver A. Cornely
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
Klaus Überla
Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany
Ulrike Protzer
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; Corresponding authors.
Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany; Corresponding authors.
Summary: 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).
