title: Immunogenicity, safety, and cross-reactivity of an inactivated, adjuvanted, prototype pandemic influenza (H5N1) vaccine: a phase II, double-blind, randomized trial.
abstract: BACKGROUND
  Avian influenza A virus H5N1 has the potential to cause a pandemic. Adjuvants and whole-virion vaccines are regarded as antigen sparing for pandemic vaccines.
  
  
  METHODS
  A double-blind, randomized trial was performed from 28 August to 22 December 2007 in 402 adults; 301 adults were randomly assigned to receive 2 doses of an inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine containing 5, 10, or 15 microg of hemagglutinin per dose 28 days apart, and 101 of them received 2 doses of 10 microg of vaccine 14 days apart. The vaccine was manufactured from the recombinant A/Vietman/1194/2004 (NIBRG14) strain. Blood samples were collected for hemagglutination inhibition and microneutralization assays.
  
  
  RESULTS
  All formulations were well tolerated, with no serious adverse events. Most local and systemic reactions were mild or moderate. Immune responses were induced after 1 dose in all vaccination groups. The highest immune response was seen after 2 doses of 15 microg of vaccine, with 90% and 100% seroconversion rates and 90% and 100% of participants having a titer of > or = 1:40 for hemagglutination inhibition and microneutralization assays, respectively. Both the 10- and 15-microg doses met or exceeded European Union licensure criteria. Generally, higher immune responses were elicited in participants vaccinated 28 days apart than those vaccinated 14 days apart. Cross-reaction assays showed that after 2 doses of 10 microg of vaccine, 98% and 87% of participants had a microneutralization titer of > or = 1:40 against heterologous Indonesia and Anhui strains, respectively.
  
  
  CONCLUSIONS
  The inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine not only showed good immunogenicity and safety but also elicited significant cross-reactivity against heterologous H5N1 strains in clade 2.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00535665.
authors.affiliation: Beijing Centers for Diseases Control and Prevention, Beijing, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.forename: Han-Hua
authors.initials: HH
authors.lastname: Fang
authors.forename: Jiang-Ting
authors.initials: JT
authors.lastname: Chen
authors.forename: Ji-Chen
authors.initials: JC
authors.lastname: Zhou
authors.forename: Zi-Jian
authors.initials: ZJ
authors.lastname: Feng
authors.forename: Chang-Gui
authors.initials: CG
authors.lastname: Li
authors.forename: Yuan-Zheng
authors.initials: YZ
authors.lastname: Qiu
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Lu
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Liu
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Dong
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Yin
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000009:adverse effects / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood*; D003429:Cross Reactions; D004196:Disease Outbreaks / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D000536:Aluminum Hydroxide