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Immunogenicity and efficacy of heterologous ChAdOx1-BNT162b2 vaccination.
Nature. 2021 12; 600(7890):701-706.Nat

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.

Authors+Show Affiliations

CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France. Immunology laboratory, CIC1408, CHU Saint-Etienne, Saint-Etienne, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France. Campus Vétérinaire de Lyon, VetAgro Sup, Université de Lyon, Marcy-l'Etoile, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France.Occupational Health and Medicine Department, Hospices Civils de Lyon, Université Claude Bernard Lyon1, Ifsttar, UMRESTTE, UMR T_9405, Université de Lyon, Lyon, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France.Occupational Health and Medicine Department, Hospices Civils de Lyon, Université Claude Bernard Lyon1, Ifsttar, UMRESTTE, UMR T_9405, Université de Lyon, Lyon, France.Occupational Health and Medicine Department, Hospices Civils de Lyon, Université Claude Bernard Lyon1, Ifsttar, UMRESTTE, UMR T_9405, Université de Lyon, Lyon, France.Joint Research Unit Civils Hospices of Lyon-bioMérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France. Virology Laboratory, Institute of Infectious Agents, Laboratory Associated with the National Reference Centre for Respiratory Viruses, Hospices Civils de Lyon, Lyon, France.Virology Laboratory, Institute of Infectious Agents, Laboratory Associated with the National Reference Centre for Respiratory Viruses, Hospices Civils de Lyon, Lyon, France.Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS UMR5286, Université de Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, Lyon, France.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France. Virology Laboratory, Institute of Infectious Agents, Laboratory Associated with the National Reference Centre for Respiratory Viruses, Hospices Civils de Lyon, Lyon, France.No affiliation info availableCIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France. flcosset@ens-lyon.fr.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France. stephane.paul@chu-st-etienne.fr.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France. thierry.defrance@inserm.fr.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France. jacqueline.marvel@inserm.fr.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France. thierry.walzer@inserm.fr.CIRI (Centre International de Recherche en Infectiologie), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France. sophie.assant@chu-lyon.fr. Joint Research Unit Civils Hospices of Lyon-bioMérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France. sophie.assant@chu-lyon.fr.

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34673755

Citation

Pozzetto, Bruno, et al. "Immunogenicity and Efficacy of Heterologous ChAdOx1-BNT162b2 Vaccination." Nature, vol. 600, no. 7890, 2021, pp. 701-706.
Pozzetto B, Legros V, Djebali S, et al. Immunogenicity and efficacy of heterologous ChAdOx1-BNT162b2 vaccination. Nature. 2021;600(7890):701-706.
Pozzetto, B., Legros, V., Djebali, S., Barateau, V., Guibert, N., Villard, M., Peyrot, L., Allatif, O., Fassier, J. B., Massardier-Pilonchéry, A., Brengel-Pesce, K., Yaugel-Novoa, M., Denolly, S., Boson, B., Bourlet, T., Bal, A., Valette, M., Andrieu, T., Lina, B., ... Trouillet-Assant, S. (2021). Immunogenicity and efficacy of heterologous ChAdOx1-BNT162b2 vaccination. Nature, 600(7890), 701-706. https://doi.org/10.1038/s41586-021-04120-y
Pozzetto B, et al. Immunogenicity and Efficacy of Heterologous ChAdOx1-BNT162b2 Vaccination. Nature. 2021;600(7890):701-706. PubMed PMID: 34673755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunogenicity and efficacy of heterologous ChAdOx1-BNT162b2 vaccination. AU - Pozzetto,Bruno, AU - Legros,Vincent, AU - Djebali,Sophia, AU - Barateau,Véronique, AU - Guibert,Nicolas, AU - Villard,Marine, AU - Peyrot,Loïc, AU - Allatif,Omran, AU - Fassier,Jean-Baptiste, AU - Massardier-Pilonchéry,Amélie, AU - Brengel-Pesce,Karen, AU - Yaugel-Novoa,Melyssa, AU - Denolly,Solène, AU - Boson,Bertrand, AU - Bourlet,Thomas, AU - Bal,Antonin, AU - Valette,Martine, AU - Andrieu,Thibault, AU - Lina,Bruno, AU - ,, AU - Cosset,François-Loïc, AU - Paul,Stéphane, AU - Defrance,Thierry, AU - Marvel,Jacqueline, AU - Walzer,Thierry, AU - Trouillet-Assant,Sophie, Y1 - 2021/10/21/ PY - 2021/07/19/received PY - 2021/10/10/accepted PY - 2021/10/22/pubmed PY - 2022/1/11/medline PY - 2021/10/21/entrez SP - 701 EP - 706 JF - Nature JO - Nature VL - 600 IS - 7890 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/34673755/Immunogenicity_and_efficacy_of_heterologous_ChAdOx1_BNT162b2_vaccination_ DB - PRIME DP - Unbound Medicine ER -