title: A randomised, single-blind, dose-range study to assess the immunogenicity and safety of a cell-culture-derived A/H1N1 influenza vaccine in adult and elderly populations.
abstract: BACKGROUND
  Modern cell-culture production techniques and the use of adjuvants helps to ensure that the global demand for pandemic influenza vaccine can be met. This study aimed to assess the immunogenicty and safety profiles of various cell-culture-derived A/H1N1 pandemic vaccine formulations in healthy adult and elderly subjects.
  
  
  METHODS
  Adult (18-60 years) subjects (n=544) received vaccine either containing 3.75 μg of antigen with half the standard dose of MF59 (Novartis Vaccines and Diagnostics) adjuvant, 7.5 μg antigen with a full dose of MF59, or a non-adjuvanted vaccine containing 15 μg of antigen. Elderly (≥ 61 years) subjects (n=268) received either the 3.75 μg or 7.5 μg adjuvanted formulations. Two priming vaccine doses were administered 3 weeks apart, followed by a single booster dose of seasonal influenza vaccine 1 year later. Immunogenicity was assessed 3 weeks after each vaccination. The safety profile of each formulation was evaluated throughout the study.
  
  
  RESULTS
  A single primary dose of each A/H1N1 vaccine formulation was sufficient to meet all three European (CHMP) licensure criteria for pandemic influenza vaccines in adult subjects. Two licensure criteria were met after one vaccine dose in elderly subjects; two primary doses were required to meet all three criteria in this age group. The highest antibody titres were observed in response to the 7.5 μg vaccine containing a full dose of MF59 adjuvant. All subjects rapidly generated seroprotective antibody titres in response to booster vaccination.
  
  
  CONCLUSIONS
  This study identified one 3.75 μg vaccine dose containing half the standard dose of MF59 adjuvant as optimal for adults, two doses were optimal for elderly subjects. The antigen-sparing properties of MF59, and rapid, modern, cell-culture production techniques represent significant steps towards meeting the global demand for influenza vaccine.
authors.affiliation: Division of Communicable Diseases, Institute for Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hatz
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Cramer
authors.forename: André
authors.initials: A
authors.lastname: Vertruyen
authors.forename: Tino F
authors.initials: TF
authors.lastname: Schwarz
authors.forename: Frank
authors.initials: F
authors.lastname: von Sonnenburg
authors.forename: Astrid
authors.initials: A
authors.lastname: Borkowski
authors.forename: Maria
authors.initials: M
authors.lastname: Lattanzi
authors.forename: Anne Katrin
authors.initials: AK
authors.lastname: Hilbert
authors.forename: Giovanni Della
authors.initials: GD
authors.lastname: Cioppa
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D018929:Cell Culture Techniques; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007117:Immunization, Secondary; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000009:adverse effects / Q000096:biosynthesis / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011136:Polysorbates / Q000008:administration & dosage; D016037:Single-Blind Method; D013185:Squalene / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene