| Autor: |
Nieves, Wildaliz, Petersen, Hailey, Judy, Barbara M., Blumentritt, Carla A., Russell-Lodrigue, Kasi, Roy, Chad J., Torres, Alfredo G., Morici, Lisa A. |
| Zdroj: |
Clinical and Vaccine Immunology (formerly CDLI); March 2014, Vol. 21 Issue: 5 p747-754, 8p |
| Abstrakt: |
ABSTRACTThe environmental Gram-negative encapsulated bacillus Burkholderia pseudomalleiis 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. pseudomalleiis 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. pseudomalleistrains poses another hazard and a challenge to vaccine development. We demonstrated that B. pseudomalleiOMVs derived from strain 1026b afforded significant protection against septicemic infection with B. pseudomalleistrain 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. pseudomalleiOMV 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. |
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