title: 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.
abstract: 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity.
  
  
  BACKGROUND
  China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China. jszfc@vip.sina.com
authors.forename: Feng-Cai
authors.initials: FC
authors.lastname: Zhu
authors.forename: Fan-Yue
authors.initials: FY
authors.lastname: Meng
authors.forename: Jing-Xin
authors.initials: JX
authors.lastname: Li
authors.forename: Xiu-Ling
authors.initials: XL
authors.lastname: Li
authors.forename: Qun-Ying
authors.initials: QY
authors.lastname: Mao
authors.forename: Hong
authors.initials: H
authors.lastname: Tao
authors.forename: Yun-Tao
authors.initials: YT
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.forename: Kai
authors.initials: K
authors.lastname: Chu
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Chen
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Hu
authors.forename: Xing
authors.initials: X
authors.lastname: Wu
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.forename: Lin-Yang
authors.initials: LY
authors.lastname: Zhu
authors.forename: Fan
authors.initials: F
authors.lastname: Gao
authors.forename: Hui
authors.initials: H
authors.lastname: Jin
authors.forename: Yi-Juan
authors.initials: YJ
authors.lastname: Chen
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Dong
authors.forename: Yong-Chun
authors.initials: YC
authors.lastname: Liang
authors.forename: Nian-Min
authors.initials: NM
authors.lastname: Shi
authors.forename: Heng-Ming
authors.initials: HM
authors.lastname: Ge
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Sheng-Gen
authors.initials: SG
authors.lastname: Chen
authors.forename: Xing
authors.initials: X
authors.lastname: Ai
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Yu-Guo
authors.initials: YG
authors.lastname: Ji
authors.forename: Feng-Ji
authors.initials: FJ
authors.lastname: Luo
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Chen
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Zhu
authors.forename: Zheng-Lun
authors.initials: ZL
authors.lastname: Liang
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Shen
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000534:Alum Compounds; D000914:Antibodies, Viral / Q000097:blood; D002675:Child, Preschool; D004311:Double-Blind Method; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007110:Immunity, Active / Q000502:physiology; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; C041524:aluminum sulfate