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Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants.
Groß, Rüdiger; Zanoni, Michelle; Seidel, Alina; Conzelmann, Carina; Gilg, Andrea; Krnavek, Daniela; Erdemci-Evin, Sümeyye; Mayer, Benjamin; Hoffmann, Markus; Pöhlmann, Stefan; Liu, Weimin; Hahn, Beatrice H; Beil, Alexandra; Kroschel, Joris; Jahrsdörfer, Bernd; Schrezenmeier, Hubert; Kirchhoff, Frank; Münch, Jan; Müller, Janis A.
Afiliação
  • Groß R; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Zanoni M; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Seidel A; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Conzelmann C; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Gilg A; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Krnavek D; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Erdemci-Evin S; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Mayer B; Institute for Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
  • Hoffmann M; Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany.
  • Pöhlmann S; Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany.
  • Liu W; Department of Microbiology and Department of Medicine, University of Pennsylvania, Philadelphia, USA.
  • Hahn BH; Department of Microbiology and Department of Medicine, University of Pennsylvania, Philadelphia, USA.
  • Beil A; Central Department for Clinical Chemistry, University Hospital Ulm, 89081, Ulm, Germany.
  • Kroschel J; Central Department for Clinical Chemistry, University Hospital Ulm, 89081, Ulm, Germany.
  • Jahrsdörfer B; 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.
  • Schrezenmeier H; 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.
  • Kirchhoff F; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Münch J; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany; Core Facility Functional Peptidomics, Ulm University Medical Center, 89081, Ulm, Germany.
  • Müller JA; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. Electronic address: Janis.mueller@uni-ulm.de.
EBioMedicine ; 75: 103761, 2022 Jan.
Article em En | MEDLINE | ID: mdl-34929493
ABSTRACT

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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Imunização Secundária / Anticorpos Neutralizantes / SARS-CoV-2 / COVID-19 / Vacina BNT162 / ChAdOx1 nCoV-19 / Imunidade Celular Tipo de estudo: Prevalence_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: EBioMedicine Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Imunização Secundária / Anticorpos Neutralizantes / SARS-CoV-2 / COVID-19 / Vacina BNT162 / ChAdOx1 nCoV-19 / Imunidade Celular Tipo de estudo: Prevalence_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: EBioMedicine Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Alemanha