Title: Modeling the population impact of rotavirus vaccination in Shanghai: An age-structured transmission analysis, 2015–2024

Background Rotavirus is a principal etiological agent of severe acute gastroenteritis in young children, for which vaccination constitutes the cornerstone of prophylactic intervention. However, to our knowledge, few studies have comprehensively assessed the differential population impacts of alternative rotavirus vaccination strategies within China. This study was therefore conducted to quantify the effect of vaccination on the epidemiological dynamics of rotavirus-associated gastroenteritis in Shanghai. Methods An age-structured Susceptible-Infected-Recovered-Susceptible (SIRS-type) compartmental model incorporating the effects of vaccine interventions was developed. Epidemiological data on reported cases were sourced from the infectious disease surveillance system. Scenario-based simulations were employed to evaluate vaccine efficacy and the prospective outcomes of strategic adjustments to the vaccination program. Results The model demonstrated a high degree of fit with observed epidemiological data over the calibration period from July 2015 to April 2024 (R 2 = 0.747, RMSE = 58.55 cases/month; LOO R 2 = 0.423). The implementation of the RotaTeq vaccination program resulted in an estimated cumulative reduction of 20.0% (95% CI : 18.9–21.6%) in the whole population and 24.6% (95% CI : 23.0–26.5%) among children under 5 years, relative to a no-RotaTeq counterfactual. Simulations indicated that optimizing the vaccination schedule of the Lanzhou lamb rotavirus vaccine (LLR) and augmenting coverage rates are effective strategies for outbreak mitigation. The introduction of Lanzhou lamb reassortant rotavirus vaccine, live, oral, trivalent (LLR3) and oral hexavalent reassortant rotavirus vaccine (WH-HRV) would further reduce the disease burden across all age groups, potentially controlling the epidemic to a minimal endemic level post-2029. Conclusions The incidence of rotavirus-associated gastroenteritis in Shanghai exhibited a discernible downward trend between 2015 and 2024, a decline associated with substantial contribution from the introduction of the RotaTeq vaccine. The optimization of existing vaccination protocols, in conjunction with the deployment of novel vaccines, is anticipated to be crucial for achieving more comprehensive and sustained control of rotavirus transmission in Shanghai.