Peer-reviewed article

Efficacy, Immunogenicity, and Safety of Enterovirus 71 Vaccines in Children: A Systematic Review and Meta-Analysis

Guan Xing Lai, Albert Ka-Wing Au, Edmond Siu-Keung Ma · 4 Mar 2026

Abstract

Background/Objectives: Hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) may cause severe complications and death in children. It is also a common cause of outbreaks in the Asia-Pacific Region. Incidence among children 1 to <2 years was over 3000/100,000 population in China. A systematic review and meta-analysis was performed to review evidence on vaccine efficacy (VE), immunogenicity, and safety of two doses of EV71 vaccine in children. Methods: Randomized controlled trials (RCTs) comparing EV71 vaccine with placebo or with another EV71 vaccine in children and adolescents aged ≤18 years were searched on PubMed, Medline, Embase, CENTRAL, and CNKI (Chinese) in week 5 November 2024. The reference list of each study and the websites of vaccine manufacturers were also searched. The Cochrane Risk of Bias 2 tool (RoB2) was used to assess the risk of bias. VE, immunogenicity (including seropositive rate, seroconversion rate, geometric mean titer (GMT), Geometric Mean Fold Increase (GMFI)), and rate of adverse events were analyzed. Results: A total of 4199 articles were identified, and 25 studies were finally included. VE (%) against EV71 HFMD in children aged ≤5 years at 12 months was 94.8% (95%CI 87.2–97.9) for Sinovac and 90.9% (95%CI 70.4–97.2) for Wuhan Institute of Biological Products (WIBP), while the Chinese Academy of Medical Sciences (CAMS) reported 97.4% (95%CI 92.9–99.0) at 11 months. At 1 month after the second dose, 99.19% (95%CI 98.15–99.65) of children aged ≤5 years in the vaccine group were seropositive, and 96.30% (95%CI 92.71–98.17) achieved seroconversion. GMT at 1 month after the second dose in the vaccine group was 46.78 (95%CI 26.18–83.61) times that in the placebo group. GMFI at 1 month after the second dose in the vaccine group was 28.41 (95%CI 22.18–36.39) times that of the placebo group. The rate of serious adverse events (AEs) was lower in the vaccine group than the placebo group (1.23% (95%CI 0.58–2.69) vs. 1.34% (95%CI 0.58–3.07)) at 1 month after the second dose. There was no significant difference in other adverse events between the vaccine and placebo groups. Conclusions: EV71 vaccines were effective, immunogenic and safe. Areas with a high incidence of EV71 may consider introducing EV71 vaccines.