Immunopotentiation of Trivalent Influenza Vaccine When Given With VAX102, a Recombinant Influenza M2e Vaccine Fused to the TLR5 Ligand Flagellin

PLoS One. 2010 Dec 28;5(12):e14442. doi: 10.1371/journal.pone.0014442.

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.

Methodology/principal findings: 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/significance: 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.

Trial registration: ClinicalTrials.gov NCT00921973.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Double-Blind Method
  • Female
  • Flagellin / chemistry*
  • Humans
  • Influenza A virus / metabolism*
  • Influenza Vaccines / immunology*
  • Influenza Vaccines / metabolism*
  • Influenza Vaccines / therapeutic use
  • Influenza, Human / prevention & control*
  • Ligands
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / metabolism
  • Salmonella typhimurium / metabolism
  • Toll-Like Receptor 5 / metabolism*

Substances

  • Influenza Vaccines
  • Ligands
  • Recombinant Fusion Proteins
  • TLR5 protein, human
  • Toll-Like Receptor 5
  • VAX102 vaccine
  • Flagellin

Associated data

  • ClinicalTrials.gov/NCT00921973