title: Identification of a LolC homologue in Burkholderia pseudomallei, a novel protective antigen for melioidosis.
abstract: Melioidosis is an emerging disease of humans in Southeast Asia and tropical Australia. The bacterium causing this disease, Burkholderia pseudomallei, is also considered a bioterrorism agent, and as yet there is no licensed vaccine for preventing B. pseudomallei infection. In this study, we evaluated selected proteins (LolC, PotF, and OppA) of the ATP-binding cassette systems of B. pseudomallei as candidate vaccine antigens. Nonmembrane regions of the B. pseudomallei proteins were expressed and purified from Escherichia coli and then evaluated as vaccine candidates in an established mouse model of B. pseudomallei infection. When delivered with the monophosphoryl lipid A-trehalose dicorynomycolate adjuvant, the proteins stimulated antigen-specific humoral and cellular immune responses. Immunization with LolC or PotF protein domains afforded significant protection against a subsequent challenge with B. pseudomallei. The most promising vaccine candidate, LolC, provided a greater level of protection when it was administered with immune-stimulating complexes complexed with CpG oligodeoxynucleotide 10103. Immunization with LolC also protected against a subsequent challenge with a heterologous strain of B. pseudomallei, demonstrating the potential utility of this protein as a vaccine antigen for melioidosis.
authors.affiliation: Department of Molecular Microbiology, School of Biosciences, Geoffrey Pope Building, University of Exeter, Exeter, United Kingdom.
authors.forename: David N
authors.initials: DN
authors.lastname: Harland
authors.forename: Karen
authors.initials: K
authors.lastname: Chu
authors.forename: Ashraful
authors.initials: A
authors.lastname: Haque
authors.forename: Michelle
authors.initials: M
authors.lastname: Nelson
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Walker
authors.forename: Mitali
authors.initials: M
authors.lastname: Sarkar-Tyson
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Atkins
authors.forename: Benjamin
authors.initials: B
authors.lastname: Moore
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Brown
authors.forename: Gregory
authors.initials: G
authors.lastname: Bancroft
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.forename: Helen S
authors.initials: HS
authors.lastname: Atkins
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D008554:Melioidosis / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; C408982:CPG-oligonucleotide; D008050:Lipid A; D009838:Oligodeoxyribonucleotides; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C048436:monophosphoryl lipid A