title: Assessment of the immunogenicity and safety of varying doses of an MF59®-adjuvanted cell culture-derived A/H1N1 pandemic influenza vaccine in Japanese paediatric, adult and elderly subjects.
abstract: BACKGROUND
  Effective vaccination strategies are required to combat future influenza pandemics. Here we report the results of three independent clinical trials performed in Japan to assess the immunogenicity, tolerability and safety of varying doses of a cell culture-derived MF59(®)-adjuvanted A/H1N1 pandemic vaccine in healthy Japanese paediatric, adult and elderly subjects.
  
  
  METHODS
  One hundred and twenty-three children (6 months-18 years), and 200 adults (19-60 years) were randomly assigned in a 1:1 ratio to receive two doses of vaccine containing either 7.5 μg antigen with a full (9.75 mg) adjuvant dose, or 3.75 μg antigen with a half (4.875 mg) adjuvant dose. One hundred elderly (≥ 61 years) subjects received only the low antigen/adjuvant vaccine formulation. Immunogenicity was assessed by haemagglutination inhibition assay at baseline and three weeks after the first and second vaccine doses on Days 22 and 43, respectively. Solicited and unsolicited adverse reactions were recorded for seven and 21 days post-immunization, respectively.
  
  
  RESULTS
  In adult and elderly subjects, a single low antigen/adjuvant dose vaccination was sufficient to meet all of the three European licensure criteria established for influenza vaccines. One high, or two low antigen/adjuvant dose vaccinations were required to meet the licensure criteria in paediatric subjects. Both vaccine formulations were well tolerated, with the majority of adverse reactions mild to moderate in severity. None of the five serious adverse events reported throughout the three trials were considered to be vaccine-related by the investigators.
  
  
  CONCLUSIONS
  The use of MF59 adjuvant allows for much reduced vaccine antigen content, and a single dose administration schedule in adults and the elderly. The production of pandemic vaccine using modern cell culture techniques is highly advantageous in terms of the quantity, quality, and rapidity of antigen production; these benefits, in combination with the use of MF59, maximize manufacturing capacity and global vaccine supply. These data support the suitability of the investigational vaccine for use in the Japanese paediatric, adult, and elderly populations.
authors.affiliation: CPC Clinic, Medipolis Medical Research Institute, Kagoshima, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukase
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Furuie
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Ryoya
authors.initials: R
authors.lastname: Komatsu
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsushita
authors.forename: Taketsugu
authors.initials: T
authors.lastname: Minami
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suehiro
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yotsuyanagi
authors.forename: Haruko
authors.initials: H
authors.lastname: Kusadokoro
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sawata
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakura
authors.forename: Maria
authors.initials: M
authors.lastname: Lattanzi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D001709:Biotechnology / Q000379:methods; D018929:Cell Culture Techniques; D002648:Child; D002675:Child, Preschool; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D007564:Japan; D008297:Male; D008875:Middle Aged; D011136:Polysorbates / Q000008:administration & dosage / Q000009:adverse effects*; D013185:Squalene / Q000008:administration & dosage / Q000009:adverse effects*; D013678:Technology, Pharmaceutical / Q000379:methods; D014611:Vaccination / Q000379:methods; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene