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Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Protective response to subunit vaccination against intranasal Burkholderia mallei and B. pseudomallei challenge
Gregory C Whitlock1, Arpaporn Deeraksa2, Omar Qazi3
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1070 ; Department of Clinical Laboratory Sciences, University of Texas Medical Branch, Galveston, Texas 77555-1070.
Abstract:
Burkholderia mallei and B. pseudomallei are Gram-negative pathogenic bacteria, responsible for the diseases glanders and melioidosis, respectively. Furthermore, there is currently no vaccine available against these Burkholderia species. In this study, we aimed to identify protective proteins against these pathogens. Immunization with recombinant B. mallei Hcp1 (type VI secreted/structural protein), BimA (autotransporter protein), BopA (type III secreted protein), and B. pseudomallei LolC (ABC transporter protein) generated significant protection against lethal inhaled B. mallei ATCC23344 and B. pseudomallei 1026b challenge. Immunization with BopA elicited the greatest protective activity, resulting in 100% and 60% survival against B. mallei and B. pseudomallei challenge, respectively. Moreover, sera from recovered mice demonstrated reactivity with the recombinant proteins. Dendritic cells stimulated with each of the different recombinant proteins showed distinct cytokine patterns. In addition, T cells from immunized mice produced IFN-γ following in vitro re-stimulation. These results indicated therefore that it was possible to elicit cross-protective immunity against both B. mallei and B. pseudomallei by vaccinating animals with one or more novel recombinant proteins identified in B. mallei.
Insights
Researchers identified protective proteins against Burkholderia mallei and Burkholderia pseudomallei, the bacteria causing glanders and melioidosis. Immunization with specific recombinant proteins, particularly BopA, demonstrated significant cross-protective immunity in animal models.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Burkholderia mallei and B. pseudomallei cause glanders and melioidosis, respectively.
- No effective vaccines currently exist for these Gram-negative pathogens.
- Identifying protective antigens is crucial for developing new treatments.
Purpose of the Study:
- To identify novel recombinant proteins from B. mallei that can elicit protective immunity.
- To evaluate the cross-protective potential of these proteins against both B. mallei and B. pseudomallei.
Main Methods:
- Immunization of mice with recombinant B. mallei proteins (Hcp1, BimA, BopA) and B. pseudomallei LolC.
- Challenging immunized mice with lethal doses of B. mallei and B. pseudomallei.
- Assessing survival rates, antibody responses, cytokine profiles of dendritic cells, and T cell activity (IFN-γ production).
Main Results:
- Immunization with recombinant Hcp1, BimA, BopA, and LolC conferred significant protection against lethal B. mallei and B. pseudomallei challenge.
- BopA immunization provided the highest protection (100% against B. mallei, 60% against B. pseudomallei).
- Immune sera showed reactivity to recombinant proteins, and T cells produced IFN-γ upon re-stimulation.
Conclusions:
- Novel recombinant proteins from B. mallei can induce cross-protective immunity against both B. mallei and B. pseudomallei.
- BopA is a promising candidate antigen for a potential vaccine against glanders and melioidosis.
- These findings pave the way for developing effective vaccines against these serious bacterial infections.
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