Immunogenicity, Tolerability, and Safety of BA.1-Adapted BNT162b2 Vaccine in 18- to 55-Year-Olds Previously Vaccinated with BNT162b2 or Who Were COVID-19 Vaccine-Naive

INTRODUCTION: Variant-adapted COVID-19 vaccines can induce more robust immune responses against closely matched circulating variants than original vaccines. METHODS: Within a phase 3 master study, monovalent Omicron BA.1-adapted BNT162b2 (BNT162b2-BA.1) was evaluated in healthy BNT162b2-experienced (cohorts 1-2) or COVID-19 vaccine-naive (cohort 3) 18 to 55 year-olds. Primary immunogenicity endpoints in cohort 1 were geometric mean ratios (GMRs) of Omicron BA.1 neutralizing titers 1 month after BNT162b2-BA.1 to those after one BNT162b2 dose and differences in percentages of participants with Omicron BA.1 seroresponse between BNT162b2-BA.1 and BNT162b2. In cohort 2, primary immunogenicity objectives (participants without evidence of previous SARS-CoV-2 infection) were to demonstrate superiority (GMR two-sided 95% CI lower limit > 1) with respect to neutralizing titer levels and noninferiority with respect to seroresponse difference (difference two-sided 95% CI lower limit > - 5%) for BNT162b2-BA.1 versus BNT162b2. In cohort 3, primary immunogenicity objectives were to demonstrate superiority with respect to neutralizing titer levels and noninferiority with respect to seroresponse after two BNT162b2-BA.1 doses compared with participants receiving BNT162b2 in an efficacy trial. Reactogenicity and adverse event frequencies were determined. RESULTS: A total of 1471 participants were included. In cohort 1 (BNT162b2-experienced), GMRs compared with one BNT162b2 dose were 2.87 and 2.64 after one or two BNT162b2-BA.1 doses, respectively, and differences in percentages of participants with seroresponse between BNT162b2-BA.1 and BNT162b2 were 29.0% and 21.0% for one or two BNT162b2-BA.1 doses. In cohort 2 (BNT162b2-experienced), one BNT162b2-BA.1 dose met prespecified superiority and noninferiority criteria with respect to GMR and difference in percentage of participants achieving seroresponse, respectively, compared with BNT162b2. In cohort 3 (COVID-19 vaccine-naive), superiority with respect to GMR and noninferiority with respect to difference in percentage of participants achieving seroresponse of BNT162b2-BA.1 to BNT162b2 were met. BNT162b2-BA.1 and BNT162b2 safety and tolerability profiles were similar. CONCLUSIONS: Omicron BA.1-adapted COVID-19 vaccines can broaden immune responses against Omicron BA.1 SARS-CoV-2 variants. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04955626.