title: Safety and immunogenicity of an MF59(®)-adjuvanted A/H5N1 pre-pandemic influenza vaccine in adults and the elderly.
abstract: BACKGROUND
  The potential consequences of an avian influenza pandemic warrants the development of safe, highly immunogenic pre-pandemic A/H5N1 vaccines with cross-clade protection. In this randomized, controlled study we compared the immunogenicity and safety of an MF59(®)-adjuvanted (Novartis Vaccines, Marburg, Germany) A/H5N1 pre-pandemic vaccine with that of a licensed, MF59-adjuvanted, seasonal influenza vaccine.
  
  
  METHODS
  Healthy adult (18-60 years, n=3372) and elderly (≥61 years, n=275) volunteers received either an initial dose of a licensed, non-adjuvanted, trivalent, seasonal influenza vaccine (Agrippal(®)) on Day 1, followed by one dose of MF59-H5N1 study vaccine on Day 22 and a second dose of MF59-H5N1 on Day 43, or alternatively, placebo on Day 1 followed by one dose of MF59-adjuvanted seasonal reference vaccine on Day 22 and a second dose of reference vaccine on Day 43. Homologous and cross-reactive A/H5N1 antibody responses were analysed by haemagglutination inhibition (HI), single radial haemolysis (SRH), and microneutralization (MN) assays three weeks after each vaccination. Vaccine safety was assessed throughout the study.
  
  
  RESULTS
  Analysis by HI assay found that two doses of MF59-H5N1 resulted in a seroconversion rate of 56% and a geometric mean ratio (GMR) of 7.1 in adult subjects. Similar results were observed on analysis by SRH (GMR 4.03; seroconversion 78% and seroprotection 91%) and MN (seroconversion 67%) assays. These data met the European licensure criteria for influenza vaccines. No significant difference in immunogenicity was detected between the adult and elderly populations. Anti-A/H5N1 cross-clade antibodies were detected by SRH, 49% of adult and 32% of elderly subjects achieved seroconversion after the second vaccine dose. Overall, MF59-H5N1 containing 7.5μg antigen was less reactogenic than the MF59-adjuvanted trivalent seasonal vaccine which contained 15μg antigen for each component strain.
  
  
  CONCLUSIONS
  Two doses of MF59-H5N1 vaccine were well tolerated and induced adequate levels of seroprotection against homologous and cross-clade A/H5N1 virus. These data support the suitability of MF59-adjuvanted A/H5N1 vaccine for pre-pandemic use in adults and the elderly.
authors.affiliation: Vaccine Research Centre, University of Tampere Medical School, Tampere, Finland. timo.vesikari@uta.fi
authors.forename: Timo
authors.initials: T
authors.lastname: Vesikari
authors.forename: Aino
authors.initials: A
authors.lastname: Forstén
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Herbinger
authors.forename: Giovanni Della
authors.initials: GD
authors.lastname: Cioppa
authors.forename: Jenny
authors.initials: J
authors.lastname: Beygo
authors.forename: Astrid
authors.initials: A
authors.lastname: Borkowski
authors.forename: Nicola
authors.initials: N
authors.lastname: Groth
authors.forename: Mariaviviana
authors.initials: M
authors.lastname: Bennati
authors.forename: Frank
authors.initials: F
authors.lastname: von Sonnenburg
mesh_terms: D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D056738:Cross Protection; D004334:Drug Administration Schedule; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D058873:Pandemics / Q000517:prevention & control*; D014611:Vaccination; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines