Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants
Rüdiger Groß,
Michelle Zanoni,
Alina Seidel,
Carina Conzelmann,
Andrea Gilg,
Daniela Krnavek,
Sümeyye Erdemci-Evin,
Benjamin Mayer,
Markus Hoffmann,
Stefan Pöhlmann,
Weimin Liu,
Beatrice H. Hahn,
Alexandra Beil,
Joris Kroschel,
Bernd Jahrsdörfer,
Hubert Schrezenmeier,
Frank Kirchhoff,
Jan Münch,
Janis A. Müller
Affiliations
Rüdiger Groß
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany
Michelle Zanoni
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany
Alina Seidel
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany
Carina Conzelmann
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany
Andrea Gilg
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany
Daniela Krnavek
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany
Sümeyye Erdemci-Evin
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany
Benjamin Mayer
Institute for Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
Markus Hoffmann
Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany
Stefan Pöhlmann
Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany
Weimin Liu
Department of Microbiology and Department of Medicine, University of Pennsylvania, Philadelphia, USA
Beatrice H. Hahn
Department of Microbiology and Department of Medicine, University of Pennsylvania, Philadelphia, USA
Alexandra Beil
Central Department for Clinical Chemistry, University Hospital Ulm, 89081, Ulm, Germany
Joris Kroschel
Central Department for Clinical Chemistry, University Hospital Ulm, 89081, Ulm, Germany
Bernd Jahrsdörfer
Institute for Transfusion Medicine, Ulm University, 89081, Ulm, Germany; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Services Baden-Württemberg-Hessen and University Hospital Ulm, 89081, Ulm, Germany
Hubert Schrezenmeier
Institute for Transfusion Medicine, Ulm University, 89081, Ulm, Germany; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Services Baden-Württemberg-Hessen and University Hospital Ulm, 89081, Ulm, Germany
Frank Kirchhoff
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany
Jan Münch
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany; Core Facility Functional Peptidomics, Ulm University Medical Center, 89081, Ulm, Germany
Janis A. Müller
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany; Correspondence: Janis A. Müller, Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany; phone: +49 731 500 65170.
Summary: Background: Heterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited. Methods: To evaluate the reactogenicity and humoral as well as cellular immune responses towards most prevalent SARS-CoV-2 variants after a heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, we analysed a cohort of 26 clinic employees aged 25-46 (median 30.5) years who received a ChAdOx1 nCoV-19 prime followed by a BNT162b2 boost after an 8-week interval. Serological data were compared to a cohort which received homologous BNT162b2 vaccination with a 3-week interval (14 individuals aged 25-65, median 42). Findings: Self-reported solicited symptoms after ChAdOx1 nCoV-19 prime were in line with previous reports and more severe than after the BNT162b2 boost. Antibody titres increased significantly over time resulting in strong neutralization titres two weeks after the BNT162b2 boost and subsequently slightly decreased over the course of 17 weeks. At the latest time point measured, all analysed sera retained neutralizing activity against the currently dominant Delta (B.1.617.2) variant. Two weeks post boost, neutralizing activity against the Alpha (B.1.1.7) and immune-evading Beta (B.1.351) variant was ∼4-fold higher than in individuals receiving homologous BNT162b2 vaccination. No difference was observed in neutralization of Kappa (B.1.617.1). In addition, heterologous vaccination induced CD4+ and CD8+ T cells reactive to SARS-CoV-2 spike peptides of all analysed variants; Wuhan-Hu-1, Alpha, Beta, Gamma (P.1), and Delta. Interpretation: In conclusion, heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination is not associated with serious adverse events and induces potent humoral and cellular immune responses. The Alpha, Beta, Delta, and Kappa variants of spike are potently neutralized by sera from all participants and reactive T cells recognize spike peptides of all tested variants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations and also offers protection against current variants of concern. Funding: This project has received funding from the European Union's Horizon 2020 research and innovation programme, the German Research Foundation, the BMBF, the Robert Koch Institute (RKI), the Baden-Württemberg Stiftung, the county of Lower Saxony, the Ministry for Science, Research and the Arts of Baden-Württemberg, Germany, and the National Institutes of Health.
