A prematurely terminated phase 2, randomised trial to evaluate immunogenicity and reactogenicity of a single versus two-dose primary vaccination regimen of the mRNA vaccine BNT162b2 in previously SARS-CoV-2 infected children 5–11 years old (CoVacc tr

BACKGROUND: This open-label randomised phase 2 study aimed to determine whether a single versus two-dose BNT162b2 primary vaccination regimen in children 5 to 11 years old with prior SARS-CoV-2 infection was non-inferior in terms of immunogenicity and superior in terms of safety and reactogenicity. METHODS: Participants were randomly assigned (1:1) to receive either one or two doses, spaced 3 to 12-weeks. The primary endpoint was geometric mean ratio (GMR) of neutralizing antibodies against wild-type SARS-CoV-2 at 28 days post-vaccination with non-inferiority margin defined as a 1.5-fold change in geometric mean titers (GMT). Secondary endpoints included safety and reactogenicity profile and immunogenicity up to 12 months against wild-type and Variants of Concern (VOCs). RESULTS: In total 31 participants from 3 European countries (median age 9, IQR7-10) were enrolled from May 2022 to January 2024, when the trial was prematurely terminated due to declining interest in COVID-19 vaccination among age-eligible children. Of these, 15 received two doses, and 16 received one. At day 28, GMT of neutralizing antibodies against wild-type SARS-CoV-2 was 1801.1 IU/mL(95%CI:1357.9-2388.9) in the two-dose arm and 1715.5 IU/mL(95%CI:1064.2-2765.4) in the single-dose arm. However, the non-inferiority of the single-dose could not be demonstrated (GMR:0.9; 95%CI:0.5-1.6). Titers remained above 100 IU/mL in both groups at 6 and 12 months. Both schedules elicited high anti-RBD IgG titers against wild-type and neutralizing titers against BA.5 variant at day 28. Eight participants (53%) in the two-dose arm and five (31%) in the single-dose reported a systemic adverse event grade ≥ 2 (P = 0.18) within 7 days of vaccination. CONCLUSIONS: Both regimens induced robust and sustained immune responses consistent with the possibility that, in children with prior infection, a single dose functions immunologically as a booster of the humoral response. However, the premature termination renders the primary non-inferiority comparison statistically underpowered. The vaccine was well tolerated in both groups. EudraCT registration: 2021-005043-71.