title: A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis.
abstract: The environmental Gram-negative encapsulated bacillus Burkholderia pseudomallei is the causative agent of melioidosis, a disease associated with high morbidity and mortality rates in areas of Southeast Asia and northern Australia in which the disease is endemic. B. pseudomallei is also classified as a tier I select agent due to the high level of lethality of the bacterium and its innate resistance to antibiotics, as well as the lack of an effective vaccine. Gram-negative bacteria, including B. pseudomallei, secrete outer membrane vesicles (OMVs) which are enriched with multiple protein, lipid, and polysaccharide antigens. Previously, we demonstrated that immunization with multivalent B. pseudomallei-derived OMVs protects highly susceptible BALB/c mice against an otherwise lethal aerosol challenge. In this work, we evaluated the protective efficacy of OMV immunization against intraperitoneal challenge with a heterologous strain because systemic infection with phenotypically diverse environmental B. pseudomallei strains poses another hazard and a challenge to vaccine development. We demonstrated that B. pseudomallei OMVs derived from strain 1026b afforded significant protection against septicemic infection with B. pseudomallei strain K96243. OMV immunization induced robust OMV-, lipopolysaccharide-, and capsular polysaccharide-specific serum IgG (IgG1, IgG2a, and IgG3) and IgM antibody responses. OMV-immune serum promoted bacterial killing in vitro, and passive transfer of B. pseudomallei OMV immune sera protected naive mice against a subsequent challenge. These results indicate that OMV immunization provides antibody-mediated protection against acute, rapidly lethal sepsis in mice. B. pseudomallei-derived OMVs may represent an efficacious multivalent vaccine strategy against melioidosis.
authors.affiliation: Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Wildaliz
authors.initials: W
authors.lastname: Nieves
authors.forename: Hailey
authors.initials: H
authors.lastname: Petersen
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Judy
authors.forename: Carla A
authors.initials: CA
authors.lastname: Blumentritt
authors.forename: Kasi
authors.initials: K
authors.lastname: Russell-Lodrigue
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
authors.forename: Alfredo G
authors.initials: AG
authors.lastname: Torres
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Morici
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D001770:Blood Bactericidal Activity; D016957:Burkholderia pseudomallei / Q000276:immunology*; D056738:Cross Protection; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008554:Melioidosis / Q000517:prevention & control*; D008807:Mice, Inbred BALB C; D022142:Secretory Vesicles / Q000276:immunology*; D018805:Sepsis / Q000517:prevention & control*; D016019:Survival Analysis
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M