Twelve-month follow-up of immunogenicity and safety of fractional and standard booster doses of the Pfizer-BioNTech COVID-19 vaccine in adults primed with ChAdOx1, BBIBP-CorV, or GAM-CoV-Vac: a randomised controlled trial

Abstract Background COVID-19 vaccine booster doses counteract waning immunity and vaccine escape by emerging variants. We evaluated long-term immunogenicity and safety of fractional and standard BNT162b2 vaccine booster doses in Mongolia. Methods In this randomised, controlled, non-inferiority trial, adults primed with two doses of ChAdOx1-S, BBIBP-CorV, or Gam-COVID-Vac were randomised (1:1) to receive a 15μg (fractional dose) or 30μg (standard-dose) BNT162b2 booster. Geometric mean ratios (GMR) of IgG and surrogate virus neutralising test (sVNT) levels (Wuhan-Hu-1 and Omicron B.1.1.529) were compared over 12 months. SARS-CoV-2 infections, adverse and serious adverse events (SAEs) were documented. ClinicalTrials.gov Identifier: NCT05265065 . Results Of 601 participants randomised between May 27th and September 30th, 2022, 2 (0.3%) were lost to follow-up and 19 (3.2%) withdrew by 12 months. IgG levels declined from 28 days to six months, stabilising thereafter. At 12 months, IgG levels were lower in the fractional compared with standard arm for ChAdOx1-S primed participants (GMR 0.78 [95% CI 0.63 - 0.96], p=0.017). At six and 12 months, the median sVNT inhibition percentages were comparable by study arm and priming strata. Documented SARS-CoV-2 infections occurred in 25 participants (fractional dose arm n=12; standard dose arm n=13). From 28 days, 228 undocumented infections (> 1.2-fold IgG increase) occurred (fractional arms n=112; standard arm n=116). SAEs (n=41) were balanced between arms, with no severe vaccine-related AEs and SAEs were reported. Conclusions Fractional and standard dose BNT162b2 boosters demonstrated comparable immunogenicity and favourable safety. Fractional COVID-19 vaccine booster doses may improve vaccine acceptability due to lower reactogenicity.