title: Immunopotentiation of trivalent influenza vaccine when given with VAX102, a recombinant influenza M2e vaccine fused to the TLR5 ligand flagellin.
abstract: BACKGROUND
  Currently controversy exists about the immunogenicity of seasonal trivalent influenza vaccine in certain populations, especially the elderly. STF2.4×M2e (VAX102) is a recombinant fusion protein that links four copies of the ectodomain of influenza virus matrix protein 2 (M2e) antigen to Salmonella typhimurium flagellin, a TLR5 ligand. The objectives of this study were to assess the feasibility of giving VAX102 and TIV in combination in an effort to achieve greater immunogenicity and to provide cross-protection.
  
  
  RESULTS
  Eighty healthy subjects, 18-49 years old, were enrolled in May and June 2009 in a double-blind, randomized, controlled trial at two clinical sites. Subjects were randomized to receive either TIV + VAX102 or TIV + placebo. Both arms tolerated the vaccines. Pain at the injection site was more severe with TIV + VAX102. Two weeks after immunization the HAI responses to the H1 and H3 antigens of TIV were higher in those that received TIV + VAX102 than in TIV + placebo (309 vs 200 and 269 vs 185, respectively), although statistically non-significant. There was no difference in the HAI of the B antigen. In the TIV + VAX102 arm, the geometric mean M2e antibody concentration was 0.5 µg/ml and 73% seroconverted.
  
  
  CONCLUSIONS
  The combination of TIV + VAX102 has the potential to increase the immune response to the influenza A components of TIV and to provide M2e immunity which may protect against influenza A strains not contained in seasonal TIV.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00921973.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. keipp.talbot@vanderbilt.edu
authors.forename: H Keipp
authors.initials: HK
authors.lastname: Talbot
authors.forename: Michael T
authors.initials: MT
authors.lastname: Rock
authors.forename: Casey
authors.initials: C
authors.lastname: Johnson
authors.forename: Lynda
authors.initials: L
authors.lastname: Tussey
authors.forename: Uma
authors.initials: U
authors.lastname: Kavita
authors.forename: Anita
authors.initials: A
authors.lastname: Shanker
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shaw
authors.forename: David N
authors.initials: DN
authors.lastname: Taylor
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005408:Flagellin / Q000737:chemistry*; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D007252:Influenza Vaccines / Q000276:immunology* / Q000378:metabolism* / Q000627:therapeutic use; D007251:Influenza, Human / Q000517:prevention & control*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012486:Salmonella typhimurium / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000378:metabolism*
chemical_list: D007252:Influenza Vaccines; D008024:Ligands; D011993:Recombinant Fusion Proteins; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; C559063:VAX102 vaccine; D005408:Flagellin