The Lancet  
Jun 08, 2013  Volume 381  Number 9882  p1959 – 2054  e18 – 19
http://www.thelancet.com/journals/lancet/issue/current

Comment
EV71 vaccine: protection from a previously neglected disease
Nigel W Crawford, Steve M Graham
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The eagerly awaited results of a phase 3 trial of an inactivated enterovirus 71 (EV71) vaccine are reported by Feng-Cai Zhu and colleagues in The Lancet.1 EV71 is an important cause of hand, foot, and mouth disease (HFMD), but is also associated with more severe diseases in young children (aged <5 years), including aseptic meningitis and encephalitis.2 This multicentre randomised controlled trial done in China is a notable advance in protection against EV71. It included more than 10 000 participants (aged 6–35 months), with a vaccine efficacy of 90·0% (95% CI 67·1–96·9) for EV71-associated HFMD and 80·4% (58·2–90·8) for EV71-associated disease (including herpangina, neurological complications, and non-specific illnesses caused by EV71).

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
Feng-Cai Zhu, Fan-Yue Meng, Jing-Xin Li, Xiu-Ling Li, Qun-Ying Mao, Hong Tao, Yun-Tao Zhang, Xin Yao, Kai Chu, Qing-Hua Chen, Yue-Mei Hu, Xing Wu, Pei Liu, Lin-Yang Zhu, Fan Gao, Hui Jin, Yi-Juan Chen, Yu-Ying Dong, Yong-Chun Liang, Nian-Min Shi, Heng-Ming Ge, Lin Liu, Sheng-Gen Chen, Xing Ai, Zhen-Yu Zhang, Yu-Guo Ji, Feng-Ji Luo, Xiao-Qin Chen, Ya Zhang, Li-Wen Zhu, Zheng-Lun Liang, Xin-Liang Shen
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961049-1/abstract
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<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33).

Interpretation
EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity.

Funding
China’s 12—5 National Major Infectious Disease Program, Beijing Vigoo Biological.