Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

• Published in: The Lancet (British edition) 2013-06, Vol.381 (9882), p.2024-2032
• Main Authors: Zhu, Feng-Cai, MSc, Meng, Fan-Yue, MSc, Li, Jing-Xin, MSc, Li, Xiu-Ling, MSc, Mao, Qun-Ying, PhD, Tao, Hong, BS, Zhang, Yun-Tao, PhD, Yao, Xin, PhD, Chu, Kai, MSc, Chen, Qing-Hua, MSc, Hu, Yue-Mei, BS, Wu, Xing, MSc, Liu, Pei, PhD, Zhu, Lin-Yang, BS, Gao, Fan, MSc, Jin, Hui, PhD, Chen, Yi-Juan, MSc, Dong, Yu-Ying, MSc, Liang, Yong-Chun, BS, Shi, Nian-Min, MSc, Ge, Heng-Ming, BS, Liu, Lin, BS, Chen, Sheng-Gen, BS, Ai, Xing, MSc, Zhang, Zhen-Yu, BS, Ji, Yu-Guo, BS, Luo, Feng-Ji, MSc, Chen, Xiao-Qin, BS, Zhang, Ya, BS, Zhu, Li-Wen, BS, Liang, Zheng-Lun, PhD, Shen, Xin-Liang, MSc
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - adverse effects; Alum Compounds; Antibodies; Antibodies, Viral - blood; Biological and medical sciences; burden of disease; Child, Preschool; children; Double-Blind Method; Drug dosages; Enterovirus; Enterovirus A, Human - immunology; Enterovirus Infections - immunology; Enterovirus Infections - prevention & control; Family medical history; Female; General aspects; Hospitals; Humans; Illnesses; immune response; Immunity, Active - physiology; Immunogenicity; Immunology; Infant; Infectious diseases; Internal Medicine; Kaplan-Meier Estimate; Male; Medical sciences; monitoring; mouth; Safety; Vaccines; Vaccines, Inactivated - adverse effects; Vaccines, Inactivated - immunology; Viral Vaccines - adverse effects; Viral Vaccines - immunology
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(13)61049-1

Summary Background A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. Methods We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6–35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov , number NCT01508247. Findings 10 245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1–96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2–90·8) against EV71-associated disease (p