Immunogenicity and efficacy of heterologous ChAdOx1–BNT162b2 vaccination

Bruno Pozzetto, Vincent Legros, Sophia Djebali, Véronique Barateau, Nicolas Guibert, Marine Villard, Loïc Peyrot, Omran Allatif, Jean-Baptiste Fassier, Amélie Massardier-Pilonchéry, Karen Brengel-Pesce, Melyssa Yaugel-Novoa, Solène Denolly, Bertrand Boson, Thomas Bourlet, Antonin Bal, Martine Valette, Thibault Andrieu, Bruno Lina, François-Loïc Cosset (), Stéphane Paul (), Thierry Defrance (), Jacqueline Marvel (), Thierry Walzer () and Sophie Trouillet-Assant ()
Additional contact information
Bruno Pozzetto: Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne
Vincent Legros: Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne
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
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
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

Nature, 2021, vol. 600, issue 7890, 701-706

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41586-021-04120-y

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