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 andmRNA1273, administered
fourmonths 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 ofOmicron 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.