Effectiveness of primary series, first, and second booster vaccination of monovalent mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections and severe diseases during the SARS-CoV-2 omicron BA.5 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

Background: This study aimed to evaluate VE of primary, first, and second booster ancestral-strain monovalent mRNA COVID-19 vaccination against symptomatic infections and severe diseases in Japan.

Methods: We conducted a test-negative case-control study. We included medically attended episodes and hospitalizations involving individuals aged $\ge$16 with signs and symptoms from July to November 2022, when Omicron BA.5 was dominant nationwide. To evaluate VE, we calculated adjusted ORs of vaccination among test-positive versus test-negative individuals using a mixed-effects logistic regression.

Results: For VE against symptomatic infections among individuals aged 16 to 59, VE of primary vaccination at > 180 days was 26.1% (95% CI: 10.6-38.8%); VE of the first booster was 58.5% (48.4-66.7%) at $\le$90 days, decreasing to 41.1% (29.5-50.8%) at 91 to 180 days. For individuals aged $\ge$60, VE of the first booster was 42.8% (1.7-66.7%) at $\le$90 days, dropping to 15.4% (-25.9-43.2%) at 91 to 180 days, and then increasing to 44.0% (16.4-62.5%) after the second booster. For VE against severe diseases, VE of the first and second booster was 77.3% (61.2-86.7%) at $\le$90 days and 55.9% (23.4-74.6%) afterward.

Conclusion: mRNA booster vaccination provided moderate protection against symptomatic infections and high-level protection against severe diseases during the BA.5 epidemic in Japan.