Reduction of adverse reactions and correlation between post-vaccination fever and specific antibody response across successive SARS-CoV-2 mRNA vaccinations

Background: SARS-CoV-2 mRNA vaccination, recognized for high immunogenicity, frequently induces adverse reactions, especially fever. We previously reported a correlation between post-vaccination fever and specific antibody responses to the primary series and first booster. We herein report changes in adverse reactions and the correlation between post-vaccination fever and antibody responses across successive vaccinations, from monovalent to bivalent mRNA vaccines. Methods: This cohort study was conducted at a Japanese hospital to investigate adverse reactions to the monovalent primary, first booster, and BA.4/5 bivalent BNT162b2 vaccinations. Local and systemic reactions were reported through a self-reporting diary after each dose. The spike-specific IgG titers were measured following each vaccination. Results: Across 727 vaccinations in the vaccine series, the bivalent booster induced fewer adverse reactions than earlier doses. Fever ≥ 38.0 °C was significantly less frequent in the bivalent booster (12.3 %) compared to the primary series and monovalent booster (22.0 %, 26.2 %, p