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

Wildaliz Nieves, Hailey Petersen, Barbara M. Judy, Carla A. Blumentritt, Kasi Russell-Lodrigue, Chad J. Roy, Alfredo G. Torres, Lisa A. Morici

Research output: Contribution to journalArticle

46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)747-754
Number of pages8
JournalClinical and Vaccine Immunology
Volume21
Issue number5
DOIs
StatePublished - May 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

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    Nieves, W., Petersen, H., Judy, B. M., Blumentritt, C. A., Russell-Lodrigue, K., Roy, C. J., Torres, A. G., & Morici, L. A. (2014). A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis. Clinical and Vaccine Immunology, 21(5), 747-754. https://doi.org/10.1128/CVI.00119-14