title: Safety and immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1) vaccine: a phase I randomised controlled trial.
abstract: BACKGROUND
  Avian influenza A virus H5N1 has caused widespread infections that have resulted in severe disease or death in poultry and wild birds as well as human beings. This virus has the potential to emerge as a pandemic threat and H5N1 vaccines are being developed in many countries. Our aim was to assess the safety and immunogenicity of an inactivated adjuvanted whole-virion H5N1 vaccine.
  
  
  METHODS
  A stratified randomised, placebo-controlled, double-blind phase I clinical trial was done in 120 volunteers aged 18-60 years. Volunteers were assigned to receive two doses of placebo (n=24) or an inactivated whole-virion influenza A (H5N1) vaccine with 1.25 microg (24), 2.5 microg (24), 5 microg (24), or 10 microg (24) haemagglutinin per dose with aluminium hydroxide adjuvant on day 0 and 28. Serum samples were obtained on day 0, 14, 28, 42, and 56 for haemagglutination inhibition and virus neutralisation assays. This trial is registered with the ClinicalTrials.gov registry with the number NCT00356798.
  
  
  RESULTS
  All four formulations of vaccines were well tolerated. No serious adverse event was reported and most local and systemic reactions were mild and transient. All formulations induced antibody responses after the first dose; the highest immune response of 78% seropositivity was seen in the 10 mug group after two vaccine doses. Two individuals dropped out: one in the 1.25 microg group (withdrew consent) and one in the 10 microg group (discontinued); one individual was also excluded from the final analysis.
  
  
  CONCLUSIONS
  A two-dose regimen of an adjuvanted 10 microg inactivated whole-virion H5N1 vaccine met all European regulatory requirements for annual licensing of seasonal influenza vaccine. Lower doses of this vaccine could achieve immune responses equivalent to those elicited by adjuvanted or non-adjuvanted split-virion vaccines. The use of a whole virion vaccine could be more adaptable to the antigen-sparing strategy recommended by WHO for protection against an influenza pandemic.
authors.affiliation: Chinese-Japanese Friendship Hospital, Beijing, China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Lin
authors.forename: Jiansan
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Dong
authors.forename: Hanhua
authors.initials: H
authors.lastname: Fang
authors.forename: Jiangting
authors.initials: J
authors.lastname: Chen
authors.forename: Nan
authors.initials: N
authors.lastname: Su
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.forename: Zhenshan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.forename: Ruihua
authors.initials: R
authors.lastname: Sun
authors.forename: Changgui
authors.initials: C
authors.lastname: Li
authors.forename: Su
authors.initials: S
authors.lastname: Lin
authors.forename: Mei
authors.initials: M
authors.lastname: Ji
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Wood
authors.forename: Zijian
authors.initials: Z
authors.lastname: Feng
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Weidong
authors.initials: W
authors.lastname: Yin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006387:Hemagglutination, Viral; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D015164:Vaccines, Inactivated
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D000536:Aluminum Hydroxide