Real-World Effectiveness of Egg-Based Inactivated Influenza Vaccines Against Influenza Among Children Aged 6-59 Months During the 2025/26 Season in Shenzhen Area, China: A Retrospective Cohort Study.

Background: Young children are at high risk of influenza and its complications, yet evidence on the real-world effectiveness of egg-based inactivated influenza vaccines in children aged 6-59 months remains limited during antigenically drifted seasons. Methods: We conducted a population-based retrospective cohort study using linked immunization and influenza surveillance records from 4 August 2025 to 8 February 2026. Vaccinated and unvaccinated children aged 6-59 months were matched 1:1 using propensity scores based on demographic characteristics, routine and non-routine vaccination history, prior seasonal influenza vaccination (SIV), and prior influenza infection. For vaccinated children, the index date was defined as the date of the last SIV received during the study period; matched unvaccinated children were assigned the corresponding index date. Follow-up began 14 days later and continued until influenza onset or 8 February 2026. Adjusted vaccine effectiveness (aVE) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Sensitivity analyses included a negative control outcome analysis using varicella infection, a multivariable logistic regression analysis with influenza infection as the outcome, and a time-dependent exposure Cox regression analysis in the full eligible cohort. Results: A total of 26,444 children were included in the final cohort (13,239 vaccinated and 13,205 unvaccinated). Influenza incidence rates were 28.70 and 40.21 per 100 person-years in vaccinated and unvaccinated groups, respectively. The aVE was 28.82% (95% CI: 23.07-34.14%). aVE was generally consistent across most subgroups, but was lower in children vaccinated in the previous season than in those without prior-season vaccination (20.41% vs. 34.28%; p for interaction = 0.016). Sensitivity analyses yielded comparable VE estimates. Conclusions: Egg-based inactivated influenza vaccination conferred moderate real-world protection against influenza in children aged 6-59 months during the 2025/26 season. Continued monitoring of vaccine effectiveness is needed to inform vaccination strategies in young children.