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Immunogenicity and efficacy of heterologous ChAdOx1–BNT162b2 vaccination

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  • Bruno Pozzetto

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne
    CIC1408, CHU Saint-Etienne)

  • Vincent Legros

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne
    Université de Lyon)

  • Sophia Djebali

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Véronique Barateau

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Nicolas Guibert

    (Université de Lyon)

  • Marine Villard

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Loïc Peyrot

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Omran Allatif

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Jean-Baptiste Fassier

    (Université de Lyon)

  • Amélie Massardier-Pilonchéry

    (Université de Lyon)

  • Karen Brengel-Pesce

    (Hospices Civils de Lyon, Lyon Sud Hospital)

  • Melyssa Yaugel-Novoa

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Solène Denolly

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Bertrand Boson

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Thomas Bourlet

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Antonin Bal

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne
    Laboratory Associated with the National Reference Centre for Respiratory Viruses, Hospices Civils de Lyon)

  • Martine Valette

    (Laboratory Associated with the National Reference Centre for Respiratory Viruses, Hospices Civils de Lyon)

  • Thibault Andrieu

    (INSERM U1052, CNRS UMR5286, Université de Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard)

  • Bruno Lina

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne
    Laboratory Associated with the National Reference Centre for Respiratory Viruses, Hospices Civils de Lyon)

  • François-Loïc Cosset

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Stéphane Paul

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Thierry Defrance

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Jacqueline Marvel

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Thierry Walzer

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne)

  • Sophie Trouillet-Assant

    (Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne
    Hospices Civils de Lyon, Lyon Sud Hospital)

Abstract

Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine1,2, European health authorities recommended that patients under the age of 55 years who received one dose of ChAdOx1-S-nCoV-19 receive a second dose of the Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here we show that the heterologous ChAdOx1-S-nCoV-19 and BNT162b2 combination confers better protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the homologous BNT162b2 and BNT162b2 combination in a real-world observational study of healthcare workers (n = 13,121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody responses, but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential correlated with increased frequencies of switched and activated memory B cells that recognize the SARS-CoV-2 receptor binding domain. The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immunocompromised individuals.

Suggested Citation

  • Bruno Pozzetto & Vincent Legros & Sophia Djebali & Véronique Barateau & Nicolas Guibert & Marine Villard & Loïc Peyrot & Omran Allatif & Jean-Baptiste Fassier & Amélie Massardier-Pilonchéry & Karen Br, 2021. "Immunogenicity and efficacy of heterologous ChAdOx1–BNT162b2 vaccination," Nature, Nature, vol. 600(7890), pages 701-706, December.
  • Handle: RePEc:nat:nature:v:600:y:2021:i:7890:d:10.1038_s41586-021-04120-y
    DOI: 10.1038/s41586-021-04120-y
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    Cited by:

    1. Gudmundur L. Norddahl & Pall Melsted & Kristbjorg Gunnarsdottir & Gisli H. Halldorsson & Thorunn A. Olafsdottir & Arnaldur Gylfason & Mar Kristjansson & Olafur T. Magnusson & Patrick Sulem & Daniel F., 2022. "Effect of booster vaccination against Delta and Omicron SARS-CoV-2 variants in Iceland," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Milja Belik & Pinja Jalkanen & Rickard Lundberg & Arttu Reinholm & Larissa Laine & Elina Väisänen & Marika Skön & Paula A. Tähtinen & Lauri Ivaska & Sari H. Pakkanen & Hanni K. Häkkinen & Eeva Ortamo , 2022. "Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    3. Verena Klemis & Tina Schmidt & David Schub & Janine Mihm & Stefanie Marx & Amina Abu-Omar & Laura Ziegler & Franziska Hielscher & Candida Guckelmus & Rebecca Urschel & Stefan Wagenpfeil & Sophie Schne, 2022. "Comparative immunogenicity and reactogenicity of heterologous ChAdOx1-nCoV-19-priming and BNT162b2 or mRNA-1273-boosting with homologous COVID-19 vaccine regimens," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Georg M. N. Behrens & Joana Barros-Martins & Anne Cossmann & Gema Morillas Ramos & Metodi V. Stankov & Ivan Odak & Alexandra Dopfer-Jablonka & Laura Hetzel & Miriam Köhler & Gwendolyn Patzer & Christo, 2022. "BNT162b2-boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Laura Pérez-Alós & Jose Juan Almagro Armenteros & Johannes Roth Madsen & Cecilie Bo Hansen & Ida Jarlhelt & Sebastian Rask Hamm & Line Dam Heftdal & Mia Marie Pries-Heje & Dina Leth Møller & Kamille F, 2022. "Modeling of waning immunity after SARS-CoV-2 vaccination and influencing factors," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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