Abstract

BACKGROUND: The emergence of SARS-CoV2 variants combined with waning vaccine-induced immunity and breakthrough infections has highlighted the need for booster doses to maintain protection against SARS-CoV2 infection and disease. METHODS: Com-COV3 was a phase II, multicentre, randomised controlled trial, recruiting across 11 UK sites from June 2022 to June 2023, with follow-up visits to February 2024. Healthy 12-15-year-olds who had received a two-30 μg dose BNT162b2 primary regimen at least 90 days previously were randomised 1:1:1:1:1 to receive either BNT162b2 30 μg, BNT162b2 10 μg (adult vaccine formulation), BNT162b2 10 μg (paediatric formulation), NVXCoV2373, or Meningococcal B vaccine (control). The primary objective was to determine if SARS-CoV-2 anti-spike antibody following a 10 μg dose of the adult formulation of BNT162b2 was non-inferior to the paediatric formulation at 28 days post-third vaccination. The last five participants were randomised using a 1:3:3:1:1 ratio to prioritise recruitment to the study groups required for the co-primary endpoint. Although recruitment ceased early, the sample size required to fulfil the primary objective was met. FINDINGS: 281 participants were recruited (mean age 14 years old, 57% female). Adverse reactions were mostly mild-to-moderate. Local reactogenicity was mildest following NVXCoV2373. Frequency of adverse events was similar for both full dose and fractional dose BNT162b2 groups. Four serious adverse events occurred: three in the paediatric and one in the adult 10 μg BNT162b2 group. Immunogenicity of 10 μg BNT162b2 (adult) was both non-inferior and superior to that of 10 μg BNT162b2 (paediatric); adjusted geometric mean ratio (aGMR) anti-spike IgG 1.50 (one-sided 95% CI 1.25 to ∞). Compared with 30 μg BNT162b2, anti-spike IgG at day 28 post-third dose were similar in the 10 μg BNT162b2 (adult) group [aGMR 0.93 (95% CI 0.75-1.14)] and significantly lower in the 10 μg BNT162b2 (paediatric) [aGMR 0.64 (95% CI 0.52-0.78)] and NVXCoV2373 [aGMR 0.77 (95% CI 0.63-0.95)] groups. Compared with 30 μg BNT162b2, levels of neutralising antibodies against Omicron BA.5 and XBB.15 were similar across vaccine groups. INTERPRETATION: All booster regimens evaluated elicited a robust immune response. 10 μg fractional adult BNT162b2 vaccine demonstrated similar immunogenicity compared with 30 μg BNT162b2 and superior immunogenicity compared with 10 μg paediatric BNT162b2 vaccine. Fractional doses of the adult BNT162b2 vaccine are an alternative to the paediatric formulation for booster campaigns in adolescents.