Effect of BNT162b2 antigen dosage on protection against SARS-CoV-2 omicron infection

Background: Coronavirus Disease 2019 (COVID-19) vaccine antigen dosage may affect protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but direct evidence to quantify this effect is lacking. Methods: A matched, retrospective, cohort study that emulated a randomized control trial was conducted in Qatar between February 3, 2022 and November 8, 2022, to provide a head-to-head, controlled comparison of protection induced by two antigen dosages of the BNT162b2 vaccine. The study compared incidence of omicron infection in the national cohort of adolescents 12 years of age who received the two-dose primary-series of the 30-g BNT162b2 vaccine to that in the national cohort of adolescents 11 years of age who received the two-dose primary-series of the pediatric 10-g BNT162b2 vaccine. Associations were estimated using Cox proportional-hazard regression models. Results: Among adolescents with no record of prior infection, cumulative incidence of infection was 6.0% (95% CI: 4.9-7.3%) for the 30-g cohort and 7.2% (95% CI: 6.1-8.5%) for the 10-g cohort, 210 days after the start of follow-up. Incidence during follow-up was dominated by omicron subvariants including, consecutively, BA.1/BA.2, BA.4/BA.5, BA.2.75*, and XBB. The adjusted hazard ratio comparing incidence of infection in the 30-g cohort to the 10-g cohort was 0.77 (95% CI: 0.60-0.98). Corresponding relative effectiveness was 23.4% (95% CI: 1.6-40.4%). Relative effectiveness was -3.3% (95% CI: -68.0-27.5%) among adolescents with a record of prior infection. Conclusions: Three-fold higher BNT162b2 dosage was associated with ~25% higher protection against infection in infection-naive adolescents of similar age. These findings may inform design of future COVID-19 vaccines and boosters for persons of different age groups.