Background and objectives: Quadrivalent live attenuated influenza vaccines (LAIV-4) offer an alternative to inactivated influenza vaccines (IIV) for children aged 2-17 years, but data on their comparative effectiveness are limited. This study assessed vaccination rates and real-world effectiveness of LAIV-4 and IIV in preventing influenza and influenza-like illness (ILI) in Italian children during the 2022-2023 and 2023-2024 seasons. Methods: We conducted a population-based cohort study of children aged 2-14 years from September 2022 to April 2024, using data from Pedianet, a pediatric primary care database of anonymized records from family pediatricians. Children vaccinated with LAIV-4 or IIV were compared to unvaccinated children. The primary outcome was any first influenza or ILI episode. Monthly vaccination incidence rates per 1,000 person-months were calculated for each vaccine type. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for vaccine effectiveness (VE) were estimated using adjusted mixed-effects Cox models. Results: A total of 65,545 (472,173 person-months) and 72,377 (527,348 person-months) children were included for the 2022-2023 and 2023-2024 seasons, respectively. Vaccination rates were 12.71 and 12.85 per 1,000 person-months, respectively. Compared to unvaccinated children, LAIV-4 had an overall effectiveness of 43% (95% CI, 32%-53%), while IIV effectiveness was 54% (95% CI, 46%-61%). In 2022-2023, LAIV-4 (38% [95% CI, 12%-56%]) and IIV (49% [95% CI, 37%-58%]) had comparable effectiveness. In 2023-2024, LAIV-4 (40% [95% CI, 25%-52%]) was slightly less effective than IIV (58% [95% CI, 44%-68%])(p=0.048). Conclusions: An overall moderate, comparable effectiveness of LAIV-4 and IIV in preventing influenza/ILI among Italian children was observed.

The authors have declared no competing interest.

This work is partially supported by CARICE (COVID-19 and Acute Respiratory Infections: the Clinical and Epidemiological changes in the pediatric population) project, which is funded by the Ministry of University and Research within the PRIN 2022 PNRR.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Inclusion in the Pedianet database is voluntary, and parents/legal guardians must provide general consent for their children's anonymized data to be stored and used for research purposes. The Internal Scientific Committee of Societa' Serivizi Telematici Srl, the legal owner of Pedianet granted ethical approval of the study and access to the database.

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Data produced in the present study are available upon reasonable request to the corresponding author