title: Immunity and clinical efficacy of an inactivated enterovirus 71 vaccine in healthy Chinese children: a report of further observations.
abstract: BACKGROUND
  To investigate the long-term effects on immunity of an inactivated enterovirus 71 (EV71) vaccine and its protective efficacy.
  
  
  METHODS
  A sub-cohort of 1,100 volunteers from Guangxi Province in China was eligible for enrolment and randomly administered either the EV71 vaccine or a placebo on days 0 and 28 in a phase III clinical trial and then observed for the following 2 years with approval by an independent ethics committee of Guangxi Zhuang Autonomous Region, China. Serum samples from the 350 participants who provided a full series of blood samples (at all the sampling points) within the 2-year period were collected. Vaccine-induced immune effects, including the neutralizing antibody titres and cross-protection against different genotypes of EV71, were examined. This study also evaluated the protective efficacy of this vaccine based upon clinical diagnosis.
  
  
  RESULTS
  This sub-cohort showed a >60% drop-out rate over 2 years. The seroconversion rates among the 161 immunized subjects remained >95% at the end of study. The geometric mean titres of neutralizing antibodies (anti-genotype C4) 360 days after vaccination in 350 subjects were 81.0 (subjects aged 6-11 months), 98.4 (12-23 months), 95.0 (24-35 months), and 81.8 (36-71 months). These titres subsequently increased to 423.1, 659.0, 545.0, and 321.9, respectively, at 540 days post-immunization (d.p.i.), and similar levels were maintained at 720 d.p.i. Higher IFN-γ/IL-4-specific responses to the C4 genotype of EV71 and cross-neutralization reactivity against major EV71 genotype strains were observed in the vaccine group compared to those in the placebo group. Five EV71-infected subjects were observed in the placebo-treated control group and none in the vaccine-immunized group in per-protocol analysis.
  
  
  CONCLUSIONS
  These results are consistent with the induction of dynamic immune responses and protective efficacy of the vaccine against most circulating EV71 strains.
  
  
  BACKGROUND
  Clinicaltrials.gov, NCT01569581, Trial registration date: March 2012.
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Longding
authors.initials: L
authors.lastname: Liu
authors.affiliation: Guangxi Province Centres for Disease Control and Prevention, Nanning, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Mo
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Zhenglun
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Guangxi Province Centres for Disease Control and Prevention, Nanning, China.
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Li
authors.affiliation: Departments of Biomedical Science and Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kien Chai
authors.initials: KC
authors.lastname: Ong
authors.affiliation: Departments of Biomedical Science and Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kum Thong
authors.initials: KT
authors.lastname: Wong
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.|Jiangsu Convac Biotechnology Co., Ltd, Taizhou, Jiangsu, China.
authors.forename: Erxia
authors.initials: E
authors.lastname: Yang
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Che
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
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authors.initials: C
authors.lastname: Dong
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Pu
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
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authors.lastname: Liao
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.|Jiangsu Convac Biotechnology Co., Ltd, Taizhou, Jiangsu, China.
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authors.lastname: Jiang
authors.affiliation: Departments of Biomedical Science and Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Soon Hao
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Institute of Health & Community Medicine, University Malaysia Sarawak, Kuala Lumpur, Malaysia.
authors.forename: Perera
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authors.lastname: David
authors.affiliation: Guangxi Province Centres for Disease Control and Prevention, Nanning, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Huang
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Medical Molecular Virology, Ministries of Education and Health, Institute of Biological Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xuanyi
authors.initials: X
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authors.affiliation: Department of Health Statistics, Fourth Military Medical University, Xi'an, China.
authors.forename: Jielai
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authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
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authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
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authors.initials: Z
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authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
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authors.forename: Qunying
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authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
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authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
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authors.initials: H
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authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
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authors.initials: R
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authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
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mesh_terms: D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D002681:China; D056738:Cross Protection; D004311:Double-Blind Method; D029821:Enterovirus A, Human / Q000276:immunology; D004769:Enterovirus Infections / Q000517:prevention & control; D016896:Treatment Outcome; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000008:administration & dosage; D014765:Viral Vaccines / Q000008:administration & dosage
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines