Incremental Effectiveness of a Second Varicella Vaccine in Children: A Prospective Cohort Study in Anhui, China

Background: Varicella remains a common vaccine-preventable disease in China. Although Anhui Province recommended a two-dose varicella vaccine (VarV) schedule in 2021, real-world evidence on the incremental benefit of the second dose is limited. Methods: A prospective cohort study among children aged 1-12 years was conducted in Anhui Province from July 2022 to August 2025. Children aged 1-3 years who had received one dose of the human diploid cell line-based (SV-1) VarV and children aged 4-12 years whose second dose was the SV-1 VarV were enrolled in the exposed group and were compared with children who had no history of VarV and those who had received only one dose of the VarV, respectively. Varicella cases were collected through active follow-up and surveillance systems. Vaccine effectiveness (VE) and incremental VE were estimated as [1 - relative risk (RR)] × 100%, where the RRs were calculated based on the incidence densities of breakthrough varicella. Results: Overall, 50,054 participants were finally enrolled, contributing 125,351.5 person-years and 105 valid cases. The VE in children aged 1-3 years was 79.1% (95%CI: 42.8-92.4%). Among children aged 4-12 years, the incremental VE was 65.0% (95%CI: 41.9-78.9%), with incremental VEs of 60.1% (95%CI: 22.3-79.5%) for ages 4-6 years and 72.7% (95%CI: 37.8-88.0%) for ages 7-12 years. Conclusions: One-dose SV-1 VarV provided substantial protection in young children, and a second dose conferred significant additional protection in children aged 4-12 years, supporting strengthened implementation of the two-dose strategy and catch-up vaccination among school-aged children.