title: A clinical phase I study of an EB66 cell-derived H5N1 pandemic vaccine adjuvanted with AS03.
abstract: BACKGROUND
  We conducted a phase I clinical trial of a cell culture-derived AS03-adjuvanted influenza vaccine containing HA antigen (A/Indonesia/05/2005(H5N1)/PR8-IBCDC-RG2) derived from EB66 cells (KD-295).
  
  
  METHODS
  Healthy male adult volunteers (20-40 years old, N=60) enrolled in the study were divided into 3 groups, the MA group (3.8 μg of HA+AS03), HA group (7.5 μg of HA+AS03), and 1/2 MA group (half the volume of the MA group), and received KD-295 intramuscularly twice with a 21-day interval. After administration of KD-295, adverse events, clinical laboratory parameters, and immune response to the vaccine strain and heterologous virus strains were evaluated.
  
  
  RESULTS
  No severe adverse events leading to discontinuation of vaccine administration occurred. The vaccine was well-tolerated. There was no dose dependency in the rate, timing, or duration of the adverse events. Immunogenicity of the vaccines was evaluated by HI (hemagglutination inhibition) assay, which confirmed that the antibody response to the vaccine strain and heterologous strain in all groups met the three criteria for immunogenicity described in the Japanese guidelines for development of a pandemic prototype vaccine. We also measured the neutralizing antibody titers against several virus strains, and confirmed a significant rise in antibody levels to both the vaccine strain and heterologous strains.
  
  
  CONCLUSIONS
  The EB66-derived H5N1 influenza vaccine adjuvanted with AS03 elicited a broad cross-reactive antibody response among H5N1 strains with acceptable reactogenicity. Therefore, KD-295 can be considered a useful pandemic and pre-pandemic influenza vaccine candidate.
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), Kumamoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Naruse
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), Kumamoto, Japan. Electronic address: fukuda@kaketsuken.or.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), Kumamoto, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Tanabe
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), Kumamoto, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Ichikawa
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), Kumamoto, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Oda
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), Kumamoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tochihara
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), Kumamoto, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kimachi
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), Kumamoto, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kino
authors.affiliation: Seinan Jo Gakuin University, Fukuoka, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Ueda
mesh_terms: D000276:Adjuvants, Immunologic; D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002460:Cell Line; D003429:Cross Reactions; D004338:Drug Combinations; D004372:Ducks; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007115:Immunization Schedule; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D007273:Injections, Intramuscular; D008297:Male; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000821:virology; D058873:Pandemics / Q000517:prevention & control; D011136:Polysorbates; D013185:Squalene / Q000276:immunology*; D055815:Young Adult; D024502:alpha-Tocopherol / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol
keywords: AS03; Cell culture-derived pandemic vaccine; EB66 cell; H5N1 influenza; JapicCTI-080586