Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants

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 ce...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:EBioMedicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352396421005557
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author 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
author_facet 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
author_sort Rüdiger Groß
collection DOAJ
description 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.
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spelling doaj.art-fcd33430a2d842e9bd5f10ff02995e222022-12-21T18:13:15ZengElsevierEBioMedicine2352-39642022-01-0175103761Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variantsRüdiger Groß0Michelle Zanoni1Alina Seidel2Carina Conzelmann3Andrea Gilg4Daniela Krnavek5Sümeyye Erdemci-Evin6Benjamin Mayer7Markus Hoffmann8Stefan Pöhlmann9Weimin Liu10Beatrice H. Hahn11Alexandra Beil12Joris Kroschel13Bernd Jahrsdörfer14Hubert Schrezenmeier15Frank Kirchhoff16Jan Münch17Janis A. Müller18Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, GermanyInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, GermanyInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, GermanyInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, GermanyInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, GermanyInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, GermanyInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, GermanyInstitute for Epidemiology and Medical Biometry, Ulm University, Ulm, GermanyInfection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, GermanyInfection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, GermanyDepartment of Microbiology and Department of Medicine, University of Pennsylvania, Philadelphia, USADepartment of Microbiology and Department of Medicine, University of Pennsylvania, Philadelphia, USACentral Department for Clinical Chemistry, University Hospital Ulm, 89081, Ulm, GermanyCentral Department for Clinical Chemistry, University Hospital Ulm, 89081, Ulm, GermanyInstitute 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, GermanyInstitute 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, GermanyInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, GermanyInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany; Core Facility Functional Peptidomics, Ulm University Medical Center, 89081, Ulm, GermanyInstitute 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.http://www.sciencedirect.com/science/article/pii/S2352396421005557COVID-19DeltaB.1.617.2immunityheterologous vaccination
spellingShingle 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
Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants
EBioMedicine
COVID-19
Delta
B.1.617.2
immunity
heterologous vaccination
title Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants
title_full Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants
title_fullStr Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants
title_full_unstemmed Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants
title_short Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants
title_sort heterologous chadox1 ncov 19 and bnt162b2 prime boost vaccination elicits potent neutralizing antibody responses and t cell reactivity against prevalent sars cov 2 variants
topic COVID-19
Delta
B.1.617.2
immunity
heterologous vaccination
url http://www.sciencedirect.com/science/article/pii/S2352396421005557
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