title: Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China.
abstract: BACKGROUND
  Enterovirus 71 (EV71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina worldwide. This phase 3 trial was designed to evaluate the efficacy, safety, and immunogenicity of an EV71 vaccine.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled, multicenter trial in which 10,007 healthy infants and young children (6 to 35 months of age) were randomly assigned in a 1:1 ratio to receive two intramuscular doses of either EV71 vaccine or placebo, 28 days apart. The surveillance period was 12 months. The primary end point was the occurrence of EV71-associated hand, foot, and mouth disease or herpangina.
  
  
  RESULTS
  During the 12-month surveillance period, EV71-associated disease was identified in 0.3% of vaccine recipients (13 of 5041 children) and 2.1% of placebo recipients (106 of 5028 children) in the intention-to-treat cohort. The vaccine efficacy against EV71-associated hand, foot, and mouth disease or herpangina was 94.8% (95% confidence interval [CI], 87.2 to 97.9; P<0.001) in this cohort. Vaccine efficacies against EV71-associated hospitalization (0 cases vs. 24 cases) and hand, foot, and mouth disease with neurologic complications (0 cases vs. 8 cases) were both 100% (95% CI, 83.7 to 100 and 42.6 to 100, respectively). Serious adverse events occurred in 111 of 5044 children in the vaccine group (2.2%) and 131 of 5033 children in the placebo group (2.6%). In the immunogenicity subgroup (1291 children), an anti-EV71 immune response was elicited by the two-dose vaccine series in 98.8% of participants at day 56. An anti-EV71 neutralizing antibody titer of 1:16 was associated with protection against EV71-associated hand, foot, and mouth disease or herpangina.
  
  
  CONCLUSIONS
  The EV71 vaccine provided protection against EV71-associated hand, foot, and mouth disease or herpangina in infants and young children. (Funded by Sinovac Biotech; ClinicalTrials.gov number, NCT01507857.).
authors.affiliation: From the Jiangsu Provincial Center for Disease Control and Prevention, Nanjing (F.Z., X.Z., Yuemei Hu, Q.L., J.L., S.W., H.W.); National Institutes for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (W.X., X.T., T.J., B.Z.), National Institutes for Food and Drug Control (Z.L., Q.M., J. Wang), and Sinovac Biotech (Y.L., J. Wu, L.S., Q.G., Yuansheng Hu, N.W.), Beijing; the Fourth Military Medical University, Xi'an (J.X., L.W.); Sheyang County Center for Disease Control and Prevention, Yancheng City (S.G., J.G., C.C.); Ganyu County Center for Disease Control and Prevention, No. 98, Lianyungang City (J.Z., X.W., M.Z.); and Taixing County Center for Disease Control and Prevention, No. 224, Taizhou City (G.Y., Y.Z., M.C.) - all in China.
authors.forename: Fengcai
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authors.forename: Wenbo
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authors.forename: Jielai
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authors.forename: Zhenglun
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authors.lastname: Liang
authors.forename: Yan
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authors.lastname: Liu
authors.forename: Xuefeng
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authors.forename: Xiaojuan
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authors.lastname: Tan
authors.forename: Ling
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authors.forename: Qunying
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authors.lastname: Mao
authors.forename: Junyu
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authors.forename: Yuemei
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authors.lastname: Hu
authors.forename: Tianjiao
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authors.forename: Lifei
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authors.forename: Qi
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authors.lastname: Liang
authors.forename: Baomin
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authors.lastname: Zhang
authors.forename: Qiang
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authors.forename: Jingxin
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authors.lastname: Li
authors.forename: Shenyu
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authors.lastname: Wang
authors.forename: Yuansheng
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authors.lastname: Hu
authors.forename: Shanru
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authors.lastname: Gu
authors.forename: Jianhua
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authors.lastname: Zhang
authors.forename: Genhong
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authors.lastname: Yao
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Gu
authors.forename: Xushan
authors.initials: X
authors.lastname: Wang
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Changbiao
authors.initials: C
authors.lastname: Chen
authors.forename: Minglei
authors.initials: M
authors.lastname: Zhang
authors.forename: Minquan
authors.initials: M
authors.lastname: Cao
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Nan
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authors.lastname: Wang
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002675:Child, Preschool; D002681:China; D004311:Double-Blind Method; D029821:Enterovirus A, Human / Q000235:genetics / Q000276:immunology*; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000276:immunology / Q000517:prevention & control*; D006557:Herpangina / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D008297:Male; D015164:Vaccines, Inactivated; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines