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

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, Laurence S. Freedman, Yitshak Kreiss, Yaniv Lustig, Gili Regev-Yochay

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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 ( NCT05231005 and NCT05230953.

Original languageEnglish
Article number7711
JournalNature Communications
Issue number1
StatePublished - 13 Dec 2022
Externally publishedYes

Bibliographical note

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


Dive into the research topics of 'Immunogenicity and efficacy of fourth BNT162b2 and mRNA1273 COVID-19 vaccine doses; three months follow-up'. Together they form a unique fingerprint.

Cite this