Comparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2

Eduardo Hermosilla; Ermengol Coma; Junqing Xie; Shuo Feng; Carmen Cabezas; Leonardo Méndez-Boo; Francesc Fina; Elisabet Ballo; Montserrat Martínez; Manuel Medina-Peralta; Josep Maria Argimon; Daniel Prieto-Alhambra

doi:10.1038/s41467-022-29301-9

Comparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2

Eduardo Hermosilla, Ermengol Coma, Junqing Xie, Shuo Feng, Carmen Cabezas, Leonardo Méndez-Boo, Francesc Fina, Elisabet Ballo, Montserrat Martínez, Manuel Medina-Peralta, Josep Maria Argimon, Daniel Prieto-Alhambra^*

^*Corresponding author for this work

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Abstract

Small trials have suggested that heterologous vaccination with first-dose ChAdOx1 and second-dose BNT162b2 may generate a better immune response than homologous vaccination with two doses of ChAdOx1. In this cohort analysis, we use linked data from Catalonia (Spain), where those aged <60 who received a first dose of ChAdOx1 could choose between ChAdOx1 and BNT162b2 for their second dose. Comparable cohorts were obtained after exact-matching 14,325/17,849 (80.3%) people receiving heterologous vaccination to 14,325/149,386 (9.6%) receiving homologous vaccination by age, sex, region, and date of second dose. Of these, 464 (3.2%) in the heterologous and 694 (4.8%) in the homologous groups developed COVID-19 between 1st June 2021 and 5th December 2021. The resulting hazard ratio (95% confidence interval) is 0.66 [0.59–0.74], favouring heterologous vaccination. The two groups had similar testing rates and safety outcomes. Sensitivity and negative control outcome analyses confirm these findings. In conclusion, we demonstrate that a heterologous vaccination schedule with ChAdOx1 followed by BNT162b2 was more efficacious than and similarly safe to homologous vaccination with two doses of ChAdOx1. Most of the infections in our study occurred when Delta was the predominant SARS-CoV-2 variant in Spain. These data agree with previous phase 2 randomised trials.

Original language	English
Article number	1639
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-29301-9
Publication status	Published - 23 Mar 2022

Bibliographical note

Funding Information:
D.P.A.’s research group has received research grants from the European Medicines Agency, from the Innovative Medicines Initiative, from Amgen, Chiesi and from UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, Astra Zeneca and UCB Biopharma. The remaining authors declare no competing interests.

Publisher Copyright:
© 2022, The Author(s).

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Comparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2Final published version, 786 KBLicence: CC BY

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Hermosilla, E., Coma, E., Xie, J., Feng, S., Cabezas, C., Méndez-Boo, L., Fina, F., Ballo, E., Martínez, M., Medina-Peralta, M., Argimon, J. M., & Prieto-Alhambra, D. (2022). Comparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2. Nature Communications, 13(1), Article 1639. https://doi.org/10.1038/s41467-022-29301-9

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title = "Comparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2",

abstract = "Small trials have suggested that heterologous vaccination with first-dose ChAdOx1 and second-dose BNT162b2 may generate a better immune response than homologous vaccination with two doses of ChAdOx1. In this cohort analysis, we use linked data from Catalonia (Spain), where those aged <60 who received a first dose of ChAdOx1 could choose between ChAdOx1 and BNT162b2 for their second dose. Comparable cohorts were obtained after exact-matching 14,325/17,849 (80.3%) people receiving heterologous vaccination to 14,325/149,386 (9.6%) receiving homologous vaccination by age, sex, region, and date of second dose. Of these, 464 (3.2%) in the heterologous and 694 (4.8%) in the homologous groups developed COVID-19 between 1st June 2021 and 5th December 2021. The resulting hazard ratio (95% confidence interval) is 0.66 [0.59–0.74], favouring heterologous vaccination. The two groups had similar testing rates and safety outcomes. Sensitivity and negative control outcome analyses confirm these findings. In conclusion, we demonstrate that a heterologous vaccination schedule with ChAdOx1 followed by BNT162b2 was more efficacious than and similarly safe to homologous vaccination with two doses of ChAdOx1. Most of the infections in our study occurred when Delta was the predominant SARS-CoV-2 variant in Spain. These data agree with previous phase 2 randomised trials.",

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note = "Funding Information: D.P.A.{\textquoteright}s research group has received research grants from the European Medicines Agency, from the Innovative Medicines Initiative, from Amgen, Chiesi and from UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, Astra Zeneca and UCB Biopharma. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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Hermosilla, E, Coma, E, Xie, J, Feng, S, Cabezas, C, Méndez-Boo, L, Fina, F, Ballo, E, Martínez, M, Medina-Peralta, M, Argimon, JM & Prieto-Alhambra, D 2022, 'Comparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2', Nature Communications, vol. 13, no. 1, 1639. https://doi.org/10.1038/s41467-022-29301-9

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AU - Hermosilla, Eduardo

AU - Coma, Ermengol

AU - Xie, Junqing

AU - Feng, Shuo

AU - Cabezas, Carmen

AU - Méndez-Boo, Leonardo

AU - Fina, Francesc

AU - Ballo, Elisabet

AU - Martínez, Montserrat

AU - Medina-Peralta, Manuel

AU - Argimon, Josep Maria

AU - Prieto-Alhambra, Daniel

N1 - Funding Information: D.P.A.’s research group has received research grants from the European Medicines Agency, from the Innovative Medicines Initiative, from Amgen, Chiesi and from UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, Astra Zeneca and UCB Biopharma. The remaining authors declare no competing interests. Publisher Copyright: © 2022, The Author(s).

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Comparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2

Abstract

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