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Published on: December 8, 2023
A naturally derived outer-membrane vesicle vaccine protects against lethal pulmonary Burkholderia pseudomallei
Wildaliz Nieves1, Saja Asakrah, Omar Qazi
1Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
Abstract:
Burkholderia pseudomallei, and other members of the Burkholderia, are among the most antibiotic-resistant bacterial species encountered in human infection. Mortality rates associated with severe B. pseudomallei infection approach 50% despite therapeutic treatment. A protective vaccine against B. pseudomallei would dramatically reduce morbidity and mortality in endemic areas and provide a safeguard for the U.S. and other countries against biological attack with this organism. In this study, we investigated the immunogenicity and protective efficacy of B. pseudomallei-derived outer membrane vesicles (OMVs). Vesicles are produced by Gram-negative and Gram-positive bacteria and contain many of the bacterial products recognized by the host immune system during infection. We demonstrate that subcutaneous (SC) immunization with OMVs provides significant protection against an otherwise lethal B. pseudomallei aerosol challenge in BALB/c mice. Mice immunized with B. pseudomallei OMVs displayed OMV-specific serum antibody and T-cell memory responses. Furthermore, OMV-mediated immunity appears species-specific as cross-reactive antibody and T cells were not generated in mice immunized with Escherichia coli-derived OMVs. These results provide the first compelling evidence that OMVs represent a non-living vaccine formulation that is able to produce protective humoral and cellular immunity against an aerosolized intracellular bacterium. This vaccine platform constitutes a safe and inexpensive immunization strategy against B. pseudomallei that can be exploited for other intracellular respiratory pathogens, including other Burkholderia and bacteria capable of establishing persistent infection.
Insights
Outer membrane vesicles (OMVs) from Burkholderia pseudomallei offer significant protection against lethal infection. This OMV-based vaccine platform demonstrates species-specific immunity and potential for other intracellular pathogens.
Area of Science:
- Bacteriology
- Immunology
- Vaccinology
Background:
- Burkholderia pseudomallei is a highly antibiotic-resistant bacterium causing severe infections with high mortality rates.
- Current treatments for B. pseudomallei infections are often insufficient, necessitating alternative protective strategies.
- A vaccine is crucial to reduce morbidity and mortality in endemic regions and protect against potential biological threats.
Purpose of the Study:
- To investigate the immunogenicity and protective efficacy of outer membrane vesicles (OMVs) derived from B. pseudomallei as a potential vaccine.
- To assess the humoral and cellular immune responses induced by B. pseudomallei OMVs.
- To determine the species specificity of the OMV-mediated immune response.
Main Methods:
- Subcutaneous immunization of BALB/c mice with B. pseudomallei-derived OMVs.
- Exposure to a lethal aerosol challenge of B. pseudomallei.
- Assessment of serum antibody levels and T-cell memory responses.
- Comparative immunization with Escherichia coli-derived OMVs to evaluate species specificity.
Main Results:
- Subcutaneous immunization with B. pseudomallei OMVs conferred significant protection against a lethal aerosol challenge.
- Immunized mice developed OMV-specific serum antibody and T-cell memory responses.
- Immunity induced by B. pseudomallei OMVs was found to be species-specific, with no cross-reactivity observed with E. coli OMVs.
Conclusions:
- B. pseudomallei-derived OMVs represent a promising non-living vaccine formulation for inducing protective humoral and cellular immunity.
- OMVs provide a safe, inexpensive, and effective immunization strategy against B. pseudomallei aerosol infection.
- This OMV vaccine platform has potential applications for other intracellular respiratory pathogens, including other Burkholderia species.
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