title: Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial.
abstract: BACKGROUND
  Helicobacter pylori is one of the most common gastric pathogens, affecting at least half the world's population, and is strongly associated with gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma. We aimed to assess the efficacy, safety, and immunogenicity of a three-dose oral recombinant H pylori vaccine in children in China.
  
  
  METHODS
  We did this randomised, double-blind, placebo-controlled, phase 3 trial at one centre in Ganyu County, Jiangsu Province, China. Healthy children aged 6-15 years without past or present H pylori infection were randomly assigned (1:1), via computer-generated randomisation codes in blocks of ten, to receive the H pylori vaccine or placebo. Participants, their guardians, and study investigators were masked to treatment allocation. The primary efficacy endpoint was the occurrence of H pylori infection within 1 year after vaccination. We did analysis in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT02302170.
  
  
  RESULTS
  Between Dec 2, 2004, and March 19, 2005, we randomly assigned 4464 participants to either the vaccine group (n=2232) or the placebo group (n=2232), of whom 4403 (99%) participants completed the three-dose vaccination schedule and were included in the per-protocol efficacy analysis. We extended follow-up to 3 years. We recorded 64 events of H pylori infection within the first year (14 events in 2074·3 person-years at risk in the vaccine group vs 50 events in 2089·6 person-years at risk in the placebo group), resulting in a vaccine efficacy of 71·8% (95% CI 48·2-85·6). 157 (7%) participants in the vaccine group and 161 (7%) participants in the placebo group reported at least one adverse reaction. Serious adverse events were reported in five (<1%) participants in the vaccine group and seven (<1%) participants in the placebo group, but none was considered to be vaccination related.
  
  
  CONCLUSIONS
  The oral recombinant H pylori vaccine was effective, safe, and immunogenic in H pylori-naive children. This vaccine could substantially reduce the incidence of H pylori infection; however, follow up over a longer period is needed to confirm the protection of the vaccine against H pylori-associated diseases.
  
  
  BACKGROUND
  Chongqing Kangwei Biological Technology.
authors.affiliation: National Institute for Food and Drug Control, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.affiliation: College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Xu-Hu
authors.initials: XH
authors.lastname: Mao
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors.forename: Jing-Xin
authors.initials: JX
authors.lastname: Li
authors.affiliation: Kangwei Biological Technology, Chongqing, China.
authors.forename: Wen-De
authors.initials: WD
authors.lastname: Tong
authors.affiliation: National Institute for Food and Drug Control, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.affiliation: National Institute for Food and Drug Control, Beijing, China.
authors.forename: Zhi-Jing
authors.initials: ZJ
authors.lastname: Zhao
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Ganyu County Center for Disease Control and Prevention, Lianyungang, Jiangsu Province, China.
authors.forename: De-Lin
authors.initials: DL
authors.lastname: Wu
authors.affiliation: College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Dong-Shui
authors.initials: DS
authors.lastname: Lu
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Tan
authors.affiliation: National Institute for Food and Drug Control, Beijing, China.
authors.forename: Hao-Yu
authors.initials: HY
authors.lastname: Liang
authors.affiliation: College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Ganyu County Center for Disease Control and Prevention, Lianyungang, Jiangsu Province, China.
authors.forename: Da-Han
authors.initials: DH
authors.lastname: Li
authors.affiliation: College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Luo
authors.affiliation: College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zeng
authors.affiliation: College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Bo-Tao
authors.initials: BT
authors.lastname: Guo
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China. Electronic address: jszfc@vip.sina.com.
authors.forename: Feng-Cai
authors.initials: FC
authors.lastname: Zhu
authors.affiliation: College of Pharmacy, Third Military Medical University, Chongqing, China. Electronic address: qmzou2007@163.com.
authors.forename: Quan-Ming
authors.initials: QM
authors.lastname: Zou
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D002648:Child; D004311:Double-Blind Method; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007110:Immunity, Active / Q000276:immunology; D008297:Male; D011994:Recombinant Proteins; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D001428:Bacterial Vaccines; D011994:Recombinant Proteins