Real-world comparison of live attenuated and inactivated influenza vaccine effectiveness in Italian children

Background Live attenuated (LAIV) and inactivated (IIV) influenza vaccines provide comparable protection in children, but differences in the timing of protection during the influenza season remain poorly characterized in real-world settings. Methods Using data from a large Italian primary care database, we conducted a retrospective population-based comparative effectiveness study comparing quadrivalent LAIV (LAIV-4) and IIV among children aged 2–14 years vaccinated during the 2023–2024 and 2024–2025 influenza seasons. Clinically diagnosed influenza and influenza-like illness (ILI) episodes were identified from clinical records. Vaccine effectiveness was assessed using time-to-event analyses based on restricted mean survival time (RMST). Results Overall effectiveness against influenza/ILI was similar between LAIV-4 and IIV across both seasons. However, temporal patterns differed, with LAIV-4 showing a trend toward earlier protection and IIV greater effectiveness during the 2023–2024 seasonal-peak. Conclusions LAIV-4 and IIV showed comparable overall effectiveness, although temporal patterns of protection varied across influenza seasons.