title: Clinical development of a Vero cell culture-derived seasonal influenza vaccine.
abstract: BACKGROUND
  Cell culture technologies have the potential to improve the robustness and flexibility of influenza vaccine supply and to substantially shorten manufacturing timelines. We investigated the safety, immunogenicity and efficacy of a Vero cell culture-derived seasonal influenza vaccine and utilized these studies to establish a serological correlate of vaccine protection.
  
  
  METHODS
  Two multicenter, randomized, double-blind phase III trials were undertaken in the US during the 2008-2009 Northern hemisphere influenza season, in young (18-49 years) and older (50-64 years and ≥ 65 years) adult subjects. 7250 young adults were randomized 1:1 to receive either Vero-derived vaccine or placebo. 3210 older adult subjects were randomized 8:1 to receive either Vero-derived vaccine or a licensed egg-derived vaccine. Serum hemagglutination inhibition antibody titers were assessed 21 days post-vaccination. Vaccine efficacy in preventing cell culture-confirmed influenza infection was determined for the young adult population. Local and systemic adverse events were recorded in both studies.
  
  
  RESULTS
  The Vero-derived vaccine was safe and well tolerated in both young and older adults. All US and European immunological licensing thresholds were comfortably met in both populations. Vaccine efficacy in young adults was 79% against A/H1N1 viruses antigenically matching the corresponding vaccine strain and 78.5% for all antigenically matched influenza viruses. A hemagglutination inhibition antibody titer of ≥ 1:15 provided a reliable correlate of protection for the Vero-derived influenza vaccine, with no additional benefit at titers >1:30. Bridging of the correlate of protection established in the young adult population to the older adult immunogenicity data demonstrated the likely effectiveness of the Vero-derived vaccine in the older adult population.
  
  
  CONCLUSIONS
  A Vero cell culture-derived seasonal influenza vaccine is safe, immunogenic and protects against infection with influenza virus. The novel vaccine technology has the potential to make a substantial contribution to improving influenza vaccine supply.
  
  
  BACKGROUND
  The studies are registered with ClinicalTrials.gov, numbers NCT00566345 and NCT00782431.
authors.affiliation: Global R&D, Baxter BioScience, IZD Tower, Wagramerstraße 17-19, A-1220 Vienna, Austria.
authors.forename: Hartmut J
authors.initials: HJ
authors.lastname: Ehrlich
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: Julia
authors.initials: J
authors.lastname: Singer
authors.forename: Daniel
authors.initials: D
authors.lastname: Portsmouth
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: P Noel
authors.initials: PN
authors.lastname: Barrett
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018929:Cell Culture Techniques; 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 / Q000096:biosynthesis*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D014709:Vero Cells; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines