title: Efficacy, safety, and immunogenicity of a Vero-cell-culture-derived trivalent influenza vaccine: a multicentre, double-blind, randomised, placebo-controlled trial.
abstract: BACKGROUND
  The use of cell-culture technologies for the manufacture of influenza vaccines might contribute to improved strain selection and robust vaccine supplies. We investigated the safety, immunogenicity, and protective efficacy of a Vero-cell-culture-derived influenza vaccine, and assessed the correlation between vaccine efficacy and haemagglutination inhibition antibody titre.
  
  
  METHODS
  In a double-blind, placebo-controlled, phase 3 trial undertaken in 36 centres in the USA, healthy adults (aged 18-49 years) were randomly assigned in a 1:1 ratio to one injection of either placebo or Vero-cell-culture-derived influenza vaccine during the 2008-09 season. Randomisation was done in blocks by use of the random number generator algorithm, and participants were allocated by use of a centralised telephone system. The primary objective was the efficacy of the vaccine in preventing cell-culture-confirmed influenza infection with viruses that were antigenically matched to one of the vaccine strains. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00566345.
  
  
  RESULTS
  7250 participants were randomly assigned to vaccine (n=3626) and placebo (n=3624). 7236 were analysed for the primary outcome (n=3619 and n=3617, respectively). Overall protective efficacy for antigenically matched influenza infection was 78·5% (95% CI 60·8-88·2). The vaccine was well tolerated with no treatment-related serious adverse events. Adverse events were mainly mild and transient. An HI titre of at least 1:15 provided a reliable correlate of cell-culture-derived influenza vaccine-induced protection; no additional benefit was noted with titres greater than 1:30.
  
  
  CONCLUSIONS
  The data indicate that existing correlates of protection afforded with egg-derived seasonal influenza vaccines also apply to this vaccine.
  
  
  BACKGROUND
  Federal (US Government) funds from the Office for Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract to DynPort Vaccine Company.
authors.affiliation: Global Research and Development, Baxter BioScience, Biomedical Research Centre, Orth/Donau, Austria. noel_barrett@baxter.com
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
authors.forename: Gregory
authors.initials: G
authors.lastname: Berezuk
authors.forename: Sandor
authors.initials: S
authors.lastname: Fritsch
authors.forename: Gerald
authors.initials: G
authors.lastname: Aichinger
authors.forename: Mary Kate
authors.initials: MK
authors.lastname: Hart
authors.forename: Wael
authors.initials: W
authors.lastname: El-Amin
authors.forename: Otfried
authors.initials: O
authors.lastname: Kistner
authors.forename: Hartmut J
authors.initials: HJ
authors.lastname: Ehrlich
mesh_terms: D000328:Adult; D000818:Animals; D002522:Chlorocebus aethiops; D004311:Double-Blind Method; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014481:United States; D014709:Vero Cells
chemical_list: D007252:Influenza Vaccines