A phase 2/3 trial to investigate the safety and immunogenicity of monovalent Omicron JN.1-adapted BNT162b2 COVID-19 vaccine in adults ≥18 years old

Background: COVID-19 remains a substantial burden in vulnerable populations, including older adults and immunocompromised individuals. It was recommended that 2024–2025 COVID-19 vaccine formulations should target a monovalent JN.1 lineage. Here we provide preliminary data on the safety, tolerability, and immunogenicity of a monovalent Omicron JN.1-adapted BNT162b2 vaccine. Methods: Fifty-three healthy adults ≥18 years old (18–55 years, n = 27; >55 years, n = 26) were vaccinated with Omicron JN.1-adapted BNT162b2. Primary safety endpoints were local reactions and systemic events through 7 days, adverse events (AEs) through 1 month, and serious AEs through 6 months; safety data through 1 month are presented here. Serum 50 % neutralizing titers against Omicron JN.1, KP.2, and KP.3, as well as XBB.1.5 were measured at baseline and 1 month after vaccination. Immunogenicity was also compared to a group who received monovalent XBB.1.5-adapted BNT162b2 in a previous substudy of this trial matched by age and baseline SARS-CoV-2 infection status to current substudy participants. Results: There were no new safety signals; local reactions and systemic events through 7 days of vaccination were generally mild to moderate in severity, and AEs were infrequent. One month after vaccination, JN.1-adapted BNT162b2 induced neutralizing titers against Omicron JN.1, KP.2, and KP.3 that were higher than those induced by XBB.1.5-adapted BNT162b2. In the JN.1-adapted BNT162b2 group, GMTs were generally similar for the 18–55- and >55-year-old age groups. Conclusion: Collectively, these safety and immunogenicity data support administration of JN.1 lineage-adapted vaccines for the 2024–2025 season. ClinicalTrials.gov