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Immunogenic Burkholderia pseudomallei outer membrane proteins as potential candidate vaccine targets
Yuka Hara1, Rahmah Mohamed, Sheila Nathan
1Malaysia Genome Institute, UKM-MTDC Smart Technology Centre, Bangi, Selangor, Malaysia.
Background:
Burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. There is no vaccine towards the bacterium available in the market, and the efficacy of many of the bacterium's surface and secreted proteins are currently being evaluated as vaccine candidates.
Methodology/Principal Findings:
With the availability of the B. pseudomallei whole genome sequence, we undertook to identify genes encoding the known immunogenic outer membrane protein A (OmpA). Twelve OmpA domains were identified and ORFs containing these domains were fully annotated. Of the 12 ORFs, two of these OmpAs, Omp3 and Omp7, were successfully cloned, expressed as soluble protein and purified. Both proteins were recognised by antibodies in melioidosis patients' sera by Western blot analysis. Purified soluble fractions of Omp3 and Omp7 were assessed for their ability to protect BALB/c mice against B. pseudomallei infection. Mice were immunised with either Omp3 or Omp7, subsequently challenged with 1x10(6) colony forming units (cfu) of B. pseudomallei via the intraperitoneal route, and examined daily for 21 days post-challenge. This pilot study has demonstrated that whilst all control unimmunised mice died by day 9 post-challenge, two mice (out of 4) from both immunised groups survived beyond 21 days post-infection.
Conclusions/Significance:
We have demonstrated that B. pseudomallei OmpA proteins are immunogenic in mice as well as melioidosis patients and should be further assessed as potential vaccine candidates against B. pseudomallei infection.
Insights
Burkholderia pseudomallei outer membrane proteins Omp3 and Omp7 show promise as vaccine candidates. Immunization with these proteins protected mice against melioidosis, indicating their potential for future vaccine development.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Melioidosis, caused by Burkholderia pseudomallei, presents a significant health burden in endemic regions.
- Current treatment options are limited, and no effective vaccine is available on the market.
Purpose of the Study:
- To identify and characterize immunogenic outer membrane proteins (OmpA) of Burkholderia pseudomallei.
- To evaluate the potential of OmpA proteins as vaccine candidates against melioidosis.
Main Methods:
- Whole genome sequencing was used to identify OmpA genes.
- Two OmpA proteins, Omp3 and Omp7, were cloned, expressed, purified, and tested for immunogenicity.
- BALB/c mice were immunized with Omp3 or Omp7 and challenged with B. pseudomallei to assess protection.
Main Results:
- Twelve OmpA domains were identified, and Omp3 and Omp7 were successfully expressed and purified.
- Both Omp3 and Omp7 were recognized by antibodies from melioidosis patients.
- Immunization with Omp3 or Omp7 resulted in the survival of two out of four mice beyond 21 days post-infection, while control mice died by day 9.
Conclusions:
- Burkholderia pseudomallei OmpA proteins (Omp3 and Omp7) are immunogenic in both mice and humans.
- These OmpA proteins demonstrate potential as vaccine candidates for melioidosis prevention.
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