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.