Immune Response and Clinical Outcomes of BNT162b2 and mRNA1273 Fourth Dose COVID-19 Vaccines; Three Months Follow-up

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. Waning of the immune response was evident during follow-up, with an 11% (ß=0.89, 95% CI, 0.88–0.9) and 21% (ß=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% (ß=0.86, 95% CI, 0.86–0.87) and 26% (ß=0.74, 95% CI, 0.72–0.76), respectively, in the BNT162b2 group. Direct neutralization of Omicron variants was low relative to ancestral strains. Cumulatively over the study period, both vaccines showed little efficacy against infection but were highly efficacious against substantial 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.