title: Protection against experimental melioidosis following immunisation with a lipopolysaccharide-protein conjugate.
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.
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Scott
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Ngugi
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Laws
authors.affiliation: Fleet Bioprocessing Ltd., Pale Lane Farm, Hartley Wintney RG27 8DH, UK.
authors.forename: David
authors.initials: D
authors.lastname: Corser
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Lonsdale
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Riccardo V
authors.initials: RV
authors.lastname: D'Elia
authors.affiliation: College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: E Diane
authors.initials: ED
authors.lastname: Williamson
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Atkins
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Joann L
authors.initials: JL
authors.lastname: Prior
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D016957:Burkholderia pseudomallei / Q000276:immunology*; D005260:Female; D056724:Immunity, Humoral / Q000187:drug effects; D007114:Immunization; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D008554:Melioidosis / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D016019:Survival Analysis; D013744:Tetanus Toxin / Q000737:chemistry / Q000276:immunology*; D058408:Th1-Th2 Balance; D018074:Vaccines, Conjugate
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D018796:Immunoconjugates; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013744:Tetanus Toxin; D018074:Vaccines, Conjugate; C040635:tetanus toxin fragment C