Protection against experimental melioidosis following immunisation with a lipopolysaccharide-protein conjugate

J Immunol Res. 2014:2014:392170. doi: 10.1155/2014/392170. Epub 2014 May 7.

Abstract

Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei. It is refractory to antibiotic treatment and there is currently no licensed vaccine. In this report we detail the construction and protective efficacy of a polysaccharide-protein conjugate composed of B. pseudomallei lipopolysaccharide and the Hc fragment of tetanus toxin. Immunisation of mice with the lipopolysaccharide-conjugate led to significantly reduced bacterial burdens in the spleen 48 hours after challenge and afforded significant protection against a lethal challenge with B. pseudomallei. The conjugate generated significantly higher levels of antigen-specific IgG1 and IgG2a than in lipopolysaccharide-immunised mice. Immunisation with the conjugate also demonstrated a bias towards Th1 type responses, evidenced by high levels of IgG2a. In contrast, immunisation with unconjugated lipopolysaccharide evoked almost no IgG2a demonstrating a bias towards Th2 type responses. This study demonstrates the effectiveness of this approach in the development of an efficacious and protective vaccine against melioidosis.

MeSH terms

  • Animals
  • Antibodies, Bacterial / biosynthesis*
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / chemistry
  • Bacterial Vaccines / immunology*
  • Burkholderia pseudomallei / immunology*
  • Female
  • Immunity, Humoral / drug effects
  • Immunization
  • Immunoconjugates / administration & dosage*
  • Immunoconjugates / chemistry
  • Immunoconjugates / immunology
  • Immunoglobulin G / biosynthesis
  • Lipopolysaccharides / chemistry
  • Lipopolysaccharides / immunology*
  • Melioidosis / immunology
  • Melioidosis / microbiology
  • Melioidosis / mortality
  • Melioidosis / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Survival Analysis
  • Tetanus Toxin / chemistry
  • Tetanus Toxin / immunology*
  • Th1-Th2 Balance
  • Vaccines, Conjugate

Substances

  • Antibodies, Bacterial
  • Bacterial Vaccines
  • Immunoconjugates
  • Immunoglobulin G
  • Lipopolysaccharides
  • Peptide Fragments
  • Recombinant Proteins
  • Tetanus Toxin
  • Vaccines, Conjugate
  • tetanus toxin fragment C