Influenza Vaccination Effectiveness Against Influenza-Associated Hospitalization in Children and the Effects of Repeated Vaccination

BACKGROUND: Given concerns that influenza vaccine effectiveness (VE) might differ with repeated annual vaccination, we estimated VE against influenza-associated hospitalization and assessed repeat vaccination effects. METHODS: We analyzed a test-negative design study conducted in 3 Hong Kong hospitals (October 2015 - July 2025), excluding the 2020/21 and 2021/22 seasons due to the absence of influenza circulation during the COVID-19 pandemic. Polymerase chain reaction testing was used to identify influenza virus infections. We used conditional logistic regression to estimate influenza VE overall, by influenza type/subtype, and by influenza vaccination status in the preceding year (repeat vaccination status). RESULTS: We analyzed data on 34 237 children, among whom 5245 (15.3%) tested positive for influenza. VE against influenza-associated hospitalization was 57.2% (95% confidence interval [CI]: 52.3%, 61.6%), with subtype-specific VE estimates of 67.7% (95% CI: 61.8%, 72.7%) for A(H1N1)pdm09, 60.6% (95% CI: 50.8%, 68.5%) for influenza B, and 37.2% (95% CI: 24.7%, 47.6%) for A(H3N2). The overall ΔVE (repeated VE - current only VE) was -13.6% (95% CI: -33.2%, 3.2%), indicating lower VE among repeatedly vaccinated children. CONCLUSIONS: Current influenza vaccination programs provide substantial protection, but could be further improved by strategies that mitigate repeat vaccination effects, and further research is needed to identify such strategies.