title: Burkholderia pseudomallei capsular polysaccharide conjugates provide protection against acute melioidosis.
abstract: Burkholderia pseudomallei, the etiologic agent of melioidosis, is a CDC tier 1 select agent that causes severe disease in both humans and animals. Diagnosis and treatment of melioidosis can be challenging, and in the absence of optimal chemotherapeutic intervention, acute disease is frequently fatal. Melioidosis is an emerging infectious disease for which there are currently no licensed vaccines. Due to the potential malicious use of B. pseudomallei as well as its impact on public health in regions where the disease is endemic, there is significant interest in developing vaccines for immunization against this disease. In the present study, type A O-polysaccharide (OPS) and manno-heptose capsular polysaccharide (CPS) antigens were isolated from nonpathogenic, select-agent-excluded strains of B. pseudomallei and covalently linked to carrier proteins. By using these conjugates (OPS2B1 and CPS2B1, respectively), it was shown that although high-titer IgG responses against the OPS or CPS component of the glycoconjugates could be raised in BALB/c mice, only those animals immunized with CPS2B1 were protected against intraperitoneal challenge with B. pseudomallei. Extending upon these studies, it was also demonstrated that when the mice were immunized with a combination of CPS2B1 and recombinant B. pseudomallei LolC, rather than with CPS2B1 or LolC individually, they exhibited higher survival rates when challenged with a lethal dose of B. pseudomallei. Collectively, these results suggest that CPS-based glycoconjugates are promising candidates for the development of subunit vaccines for immunization against melioidosis.
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom aescott2@dstl.gov.uk.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Scott
authors.affiliation: Department of Microbiology and Immunology, University of South Alabama, Mobile, Alabama, USA.
authors.forename: Mary N
authors.initials: MN
authors.lastname: Burtnick
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
authors.forename: Margaret G M
authors.initials: MG
authors.lastname: Stokes
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
authors.forename: Adam O
authors.initials: AO
authors.lastname: Whelan
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
authors.forename: E Diane
authors.initials: ED
authors.lastname: Williamson
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Atkins
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
authors.forename: Joann L
authors.initials: JL
authors.lastname: Prior
authors.affiliation: Department of Microbiology and Immunology, University of South Alabama, Mobile, Alabama, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brett
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016957:Burkholderia pseudomallei / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008554:Melioidosis / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D018074:Vaccines, Conjugate