A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis

• Published in: Clinical and vaccine immunology 2014-05, Vol.21 (5), p.747-754
• Main Authors: Nieves, Wildaliz, Petersen, Hailey, Judy, Barbara M, Blumentritt, Carla A, Russell-Lodrigue, Kasi, Roy, Chad J, Torres, Alfredo G, Morici, Lisa A
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Bacterial - blood; Bacillus; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; Blood Bactericidal Activity; Burkholderia pseudomallei; Burkholderia pseudomallei - immunology; Cross Protection; Female; Immunoglobulin G - blood; Immunoglobulin M - blood; Melioidosis - prevention & control; Mice, Inbred BALB C; Secretory Vesicles - immunology; Sepsis - prevention & control; Survival Analysis; Vaccines
• ISSN: 1556-6811; 1556-679X; 1556-679X
• DOI: 10.1128/CVI.00119-14

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.