title: Dose sparing and the lack of a dose-response relationship with an influenza vaccine in adult and elderly patients - a randomized, double-blind clinical trial.
abstract: OBJECTIVE
  The currently licensed seasonal trivalent influenza vaccines contain 15 μg haemagglutinin per strain for adult, and up to 60 μg for elderly patients. However, due to recent shortages, dose sparing to increase production capacity would be highly desirable. In the present study, we attempted to find a dose-response relationship for immunogenicity and, thus, the optimal dose for seasonal influenza vaccines in adult and elderly patients.
  
  
  METHODS
  A total of 256 subjects, including adult (aged 18-60 years) and elderly (aged over 60 years) individuals, were enrolled. Subjects were randomly assigned in a 1:1:1:1 ratio to receive a whole-virion, aluminium-adjuvanted trivalent influenza vaccine containing 3.5, 6, 9 or 15 μg haemagglutinin of seasonal A/H1N1, A/H3N2 and B influenza antigens manufactured by Omninvest Ltd., Hungary. Serum antibody titres against the vaccine virus strains were measured by haemagglutination inhibition.
  
  
  RESULTS
  All vaccines were well tolerated. All four vaccines fulfilled all three immunogenicity licensing criteria, as determined by the European Committee for Proprietary Medicinal Products (CPMP)/Biotechnology Working Party (BWP)/214/96 guideline for all three virus strains and both age groups. The 3.5 μg vaccine showed 28% less seroconversion compared to the 15 μg dose in terms of influenza AH3N2 in the adult group (95% confidence interval -51, -3; P < 0.05). All other doses showed no significant difference in immunogenicity compared with the licensed vaccine containing 15 μg haemagglutinin.
  
  
  CONCLUSIONS
  Our data suggested that significant dose sparing is possible with the use of whole-virion vaccines and aluminium adjuvants, without compromising safety. This could have significant economic and public health impacts.
authors.affiliation: Department of Family Practice, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Vajo
authors.affiliation: Department of Family Practice, Semmelweis University, Budapest, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Balaton
authors.affiliation: Medical and Health Sciences Centre, University of Debrecen, Debrecen, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Vajo
authors.affiliation: Department of Family Practice, Semmelweis University, Budapest, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kalabay
authors.affiliation: Arizona State University, Tempe, AZ, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Erdman
authors.affiliation: Department of Family Practice, Semmelweis University, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Torzsa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000071497:Immunogenicity, Vaccine / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D058248:Serum Bactericidal Antibody Assay; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines
keywords: adverse events; dose response; economics; immunology; safety; vaccine