title: Safety and immunogenicity of adjuvanted inactivated split-virion and whole-virion influenza A (H5N1) vaccines in children: a phase I-II randomized trial.
abstract: OBJECTIVE
  Highly pathogenic avian influenza A virus H5N1 has the potential to cause a pandemic. Many prototype pandemic influenza A (H5N1) vaccines had been developed and well evaluated in adults in recent years. However, data in children are limited. Herein we evaluate the safety and immunogenicity of adjuvanted split-virion and whole-virion H5N1 vaccines in children.
  
  
  METHODS
  An open-labelled phase I trial was conducted in children aged 3-11 years to receive aluminum-adjuvated, split-virion H5N1 vaccine (5-30 microg) and in children aged 12-17 years to receive aluminum-adjuvated, whole-virion H5N1 vaccine (5-15 microg). Safety of the two formulations was assessed. Then a randomized phase II trial was conducted, in which 141 children aged 3-11 years received the split-virion vaccine (10 or 15 microg) and 280 children aged 12-17 years received the split-virion vaccine (10-30 microg) or the whole-virion vaccine (5 microg). Serum samples were collected for hemagglutination-inhibition (HI) assays.
  
  
  RESULTS
  5-15 microg adjuvated split-virion vaccines were well tolerated in children aged 3-11 years and 5-30 microg adjuvated split-virion vaccines and 5 microg adjuvated whole-virion vaccine were well tolerated in children aged 12-17 years. Most local and systemic reactions were mild or moderate. Before vaccination, all participants were immunologically naïve to H5N1 virus. Immune responses were induced after the first dose and significantly boosted after the second dose. In 3-11 years children, the 10 and 15 microg split-virion vaccine induced similar responses with 55% seroconversion and seroprotection (HI titer >or=1:40) rates. In 12-17 years children, the 30 microg split-virion vaccine induced the highest immune response with 71% seroconversion and seroprotection rates. The 5 microg whole-virion vaccine induced higher response than the 10 microg split-virion vaccine did.
  
  
  CONCLUSIONS
  The aluminum-adjuvanted, split-virion prototype pandemic influenza A (H5N1) vaccine showed good safety and immunogenicity in children and 30 microg dose induced immune response complying with European Union licensure criteria.
authors.affiliation: Beijing Centers for Diseases Control and Prevention, Beijing, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.forename: Shu-Zhen
authors.initials: SZ
authors.lastname: Liu
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Dong
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
authors.forename: Wu-Li
authors.initials: WL
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Lu
authors.forename: Chang-Gui
authors.initials: CG
authors.lastname: Li
authors.forename: Ji-Chen
authors.initials: JC
authors.lastname: Zhou
authors.forename: Han-Hua
authors.initials: HH
authors.lastname: Fang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Liu
authors.forename: Yuan-Zheng
authors.initials: YZ
authors.lastname: Qiu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Jiang-Ting
authors.initials: JT
authors.lastname: Chen
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhong
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Yin
authors.forename: Zi-Jian
authors.initials: ZJ
authors.lastname: Feng
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines