Effectiveness of JN.1-adapted COVID-19 vaccine against medically attended SARS-CoV-2 infection and COVID-19 hospitalization in adults in Japan, from October 2024 to April 2025: VERSUS

BACKGROUND: Evaluating COVID-19 vaccine effectiveness (VE) is essential to guide vaccine policy as SARS-CoV-2 continues evolving. This study evaluated the effectiveness of JN.1-adapted COVID-19 vaccine (JN.1 vaccine) against medically attended symptomatic SARS-CoV-2 infection and COVID-19 hospitalization among adults in Japan. METHODS: We conducted a multicenter test-negative case-control study in Japan, from October 1, 2024-April 30, 2025. Adults aged ≥18 years with ≥1 sign or symptom of acute respiratory illness were included in symptomatic infection analysis, and adults aged ≥60 years hospitalized with ≥2 signs or symptoms of acute respiratory illness and/or radiographically confirmed pneumonia were included in hospitalization analysis. VE of JN.1 vaccine was estimated by comparing those who received with those who did not receive JN.1 vaccine, regardless of prior COVID-19 vaccination, using mixed-effects logistic regression models. RESULTS: Among 5413 episodes, VE of JN.1 vaccine against symptomatic infection was 55.1% (95% confidence interval [CI]: 35.0-69.0) at ≥7 days, 52.7% (95% CI: 22.4-71.2) at 7-60 days, and 57.6% (95% CI: 28.2-75.0) at >60 days after vaccination. VE was 61.0% (95% CI: 30.2-78.2) in adults aged 18-64 and 44.3% (95% CI: 8.4-66.1) in those aged ≥65. Among 1106 hospitalizations, VE against COVID-19 hospitalization in adults aged ≥60 was 61.8% (95% CI, 21.5-81.4) at ≥7 days after vaccination. VE against more severe disease was similar: 60.1% (95% CI: 4.0-83.4) against hospitalization with respiratory failure, 55.7% (95% CI: 8.3-78.6) against hospitalization with moderate-to-severe diseases defined by the CURB-65 score, and 66.4% (95% CI: 19.9-86.0) against hospitalization with radiographically confirmed pneumonia. CONCLUSION: JN.1 vaccines provided additional protection against both mild and severe outcomes among adults in Japan during circulation of KP.3 and XEC variants. These findings support continued vaccination of adults, particularly older adults, to mitigate the disease burden.