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 Torres, Lisa A. Morici

Research output: Contribution to journalArticle

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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 - 2014

Fingerprint

Burkholderia pseudomallei
Sepsis
Vaccines
Membranes
Immunization
Melioidosis
Immunoglobulin G
Polysaccharides
Immune Sera
Bacteria
Endemic Diseases
Southeastern Asia
Antibodies
Bacilli
Microbial Drug Resistance
Infection
Aerosols
Gram-Negative Bacteria
Bacillus
Antibody Formation

ASJC Scopus subject areas

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

Cite this

Nieves, W., Petersen, H., Judy, B. M., Blumentritt, C. A., Russell-Lodrigue, K., Roy, C. J., ... 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

A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis. / Nieves, Wildaliz; Petersen, Hailey; Judy, Barbara M.; Blumentritt, Carla A.; Russell-Lodrigue, Kasi; Roy, Chad J.; Torres, Alfredo; Morici, Lisa A.

In: Clinical and Vaccine Immunology, Vol. 21, No. 5, 2014, p. 747-754.

Research output: Contribution to journalArticle

Nieves, W, Petersen, H, Judy, BM, Blumentritt, CA, Russell-Lodrigue, K, Roy, CJ, Torres, A & Morici, LA 2014, 'A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis', Clinical and Vaccine Immunology, vol. 21, no. 5, pp. 747-754. https://doi.org/10.1128/CVI.00119-14
Nieves, Wildaliz ; Petersen, Hailey ; Judy, Barbara M. ; Blumentritt, Carla A. ; Russell-Lodrigue, Kasi ; Roy, Chad J. ; Torres, Alfredo ; Morici, Lisa A. / A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis. In: Clinical and Vaccine Immunology. 2014 ; Vol. 21, No. 5. pp. 747-754.
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