title: Effects of adjuvants on the safety and immunogenicity of an avian influenza H5N1 vaccine in adults.
abstract: BACKGROUND
  Influenza A H5N1 viruses pose a significant threat to human health.
  
  
  METHODS
  We conducted a multicenter, randomized, double-blind study in 394 healthy adults. Subjects were randomly assigned to receive 2 intramuscular doses of either saline placebo; influenza A/Vietnam/1203/2004(H5N1) vaccine alone at 45, 30, or 15 microg per dose; vaccine at 15 or 7.5 microg per dose with MF59; or vaccine at 30, 15, or 7.5 microg per dose with aluminum hydroxide. Subjects were followed up for safety and blood samples were obtained to determine antibody responses.
  
  
  RESULTS
  The vaccine formulations were well tolerated but local adverse effects were common; the incidence of these effects increased in a dose-dependent manner and was increased by the addition of adjuvants. The addition of MF59 increased the antibody response, whereas the addition of aluminum hydroxide did not. The highest antibody responses were seen in the group that received 15 microg of vaccine per dose with MF59, in which 63% of subjects achieved the predetermined endpoint (hemagglutination-inhibition titer > or =40) 28 days after the second dose, compared with 29% in the group that received the highest dose (45 microg per dose) of vaccine alone.
  
  
  CONCLUSIONS
  A 2-dose regimen of subvirion influenza A (H5N1) vaccine was well tolerated. The antibody responses to 15 microg of A/H5 vaccine with MF59 were higher than the responses to 45 microg of vaccine alone.
  
  
  BACKGROUND
  ClincalTrials.gov identifier: http://www.clinicaltrials.gov/ct2/show/NCT00280033?term= NCT00280033&rank=1 NCT00280033 .
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. david.berstein@cchmc.org
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Edwards
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
authors.forename: Robert
authors.initials: R
authors.lastname: Belshe
authors.forename: Helen K B
authors.initials: HK
authors.lastname: Talbot
authors.forename: Irene L
authors.initials: IL
authors.lastname: Graham
authors.forename: Diana L
authors.initials: DL
authors.lastname: Noah
authors.forename: Fenhua
authors.initials: F
authors.lastname: He
authors.forename: Heather
authors.initials: H
authors.lastname: Hill
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011136:Polysorbates / Q000009:adverse effects*; D013185:Squalene / Q000009:adverse effects* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D000536:Aluminum Hydroxide; D013185:Squalene