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Immunogenicity and efficacy of fourth BNT162b2 and mRNA1273 COVID-19 vaccine doses; three months follow-up

Author

Listed:
  • Michal Canetti

    (The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer
    Tel-Aviv University)

  • Noam Barda

    (ARC Innovation Center, Sheba Medical Center, Tel Hashomer
    Software and Information Systems Engineering, Ben-Gurion University of the Negev
    Harvard Medical School)

  • Mayan Gilboa

    (The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer
    Tel-Aviv University)

  • Victoria Indenbaum

    (Tel-Aviv University
    Central Virology Laboratory, Public Health Services, Ministry of Health, Tel-Hashomer)

  • Michal Mandelboim

    (Tel-Aviv University
    Central Virology Laboratory, Public Health Services, Ministry of Health, Tel-Hashomer)

  • Tal Gonen

    (The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer
    Tel-Aviv University)

  • Keren Asraf

    (Tel-Aviv University
    The Dworman Automated-Mega Laboratory, Sheba Medical Center, Tel-Hashomer)

  • Yael Weiss-Ottolenghi

    (The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer
    Tel-Aviv University)

  • Sharon Amit

    (Tel-Aviv University
    Clinical Microbiology, Sheba Medical Center, Tel Hashomer)

  • Ram Doolman

    (Tel-Aviv University
    The Dworman Automated-Mega Laboratory, Sheba Medical Center, Tel-Hashomer)

  • Ella Mendelson

    (Tel-Aviv University
    Central Virology Laboratory, Public Health Services, Ministry of Health, Tel-Hashomer)

  • Dror Harats

    (General Management, Sheba Medical Center, Tel Hashomer)

  • Laurence S. Freedman

    (Biostatistics and Biomathematics Unit, Gertner Institute of Epidemiology and Health Policy Research, Sheba Medical Center)

  • Yitshak Kreiss

    (Tel-Aviv University
    General Management, Sheba Medical Center, Tel Hashomer)

  • Yaniv Lustig

    (Tel-Aviv University
    Central Virology Laboratory, Public Health Services, Ministry of Health, Tel-Hashomer
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Gili Regev-Yochay

    (The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer
    Tel-Aviv University)

Abstract

Booster doses for the ongoing COVID-19 pandemic are under consideration in many countries. We report a three-month follow-up of 700 participants in a fourth vaccine dose study, comparing BNT162b2 and mRNA1273, administered four months after a third BNT162b2 dose. The primary outcomes are the levels of IgG, neutralizing antibodies, and microneutralization and the secondary outcomes are the levels of IgA and T cell activation, and clinical outcomes of SARS-CoV-2 infection and substantial symptomatic disease. Waning of the immune response is evident during follow-up, with an 11% (β = 0.89, 95% CI, 0.88–0.9) and 21% (β = 0.79, 95% CI, 0.76–0.82) multiplicative decay per week of IgG and neutralizing antibodies, respectively, in the mRNA1273 group, and of 14% (β = 0.86, 95% CI, 0.86–0.87) and 26% (β = 0.74, 95% CI, 0.72–0.76), respectively, in the BNT162b2 group. Direct neutralization of Omicron variants is low relative to ancestral strains. Cumulatively over the study period, both vaccines show little efficacy against infection but were highly efficacious against substantial symptomatic disease [89% [(IRR 0.11, 95% CI, 0.02–0.37) and 71% (IRR 0.29, 95% CI, 0.13–0.57) for mRNA1273 and BNT162b2, respectively]. These results are informative for further boosting policy-making. Trial registration numbers (clinicaltrials.gov): NCT05231005 and NCT05230953.

Suggested Citation

  • Michal Canetti & Noam Barda & Mayan Gilboa & Victoria Indenbaum & Michal Mandelboim & Tal Gonen & Keren Asraf & Yael Weiss-Ottolenghi & Sharon Amit & Ram Doolman & Ella Mendelson & Dror Harats & Laure, 2022. "Immunogenicity and efficacy of fourth BNT162b2 and mRNA1273 COVID-19 vaccine doses; three months follow-up," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35480-2
    DOI: 10.1038/s41467-022-35480-2
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    References listed on IDEAS

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    1. Tal Patalon & Yaki Saciuk & Asaf Peretz & Galit Perez & Yoav Lurie & Yasmin Maor & Sivan Gazit, 2022. "Waning effectiveness of the third dose of the BNT162b2 mRNA COVID-19 vaccine," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    2. Sandile Cele & Laurelle Jackson & David S. Khoury & Khadija Khan & Thandeka Moyo-Gwete & Houriiyah Tegally & James Emmanuel San & Deborah Cromer & Cathrine Scheepers & Daniel G. Amoako & Farina Karim , 2022. "Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization," Nature, Nature, vol. 602(7898), pages 654-656, February.
    3. Hiam Chemaitelly & Houssein H. Ayoub & Sawsan AlMukdad & Peter Coyle & Patrick Tang & Hadi M. Yassine & Hebah A. Al-Khatib & Maria K. Smatti & Mohammad R. Hasan & Zaina Al-Kanaani & Einas Al-Kuwari & , 2022. "Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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