Designing a novel chimeric multi-epitope vaccine against Burkholderia pseudomallei, a causative agent of melioidosis

设计一种针对类鼻疽伯克霍尔德菌(一种类鼻疽病病原体)的新型嵌合多表位疫苗

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Abstract

Burkholderia pseudomallei, a gram-negative soil-dwelling bacterium, is primarily considered a causative agent of melioidosis infection in both animals and humans. Despite the severity of the disease, there is currently no licensed vaccine on the market. The development of an effective vaccine against B. pseudomallei could help prevent the spread of infection. The purpose of this study was to develop a multi-epitope-based vaccine against B. pseudomallei using advanced bacterial pan-genome analysis. A total of four proteins were prioritized for epitope prediction by using multiple subtractive proteomics filters. Following that, a multi-epitopes based chimeric vaccine construct was modeled and joined with an adjuvant to improve the potency of the designed vaccine construct. The structure of the construct was predicted and analyzed for flexibility. A population coverage analysis was performed to evaluate the broad-spectrum applicability of B. pseudomallei. The computed combined world population coverage was 99.74%. Molecular docking analysis was applied further to evaluate the binding efficacy of the designed vaccine construct with the human toll-like receptors-5 (TLR-5). Furthermore, the dynamic behavior and stability of the docked complexes were investigated using molecular dynamics simulation, and the binding free energy determined for Vaccine-TLR-5 was delta total -168.3588. The docking result revealed that the vaccine construct may elicit a suitable immunological response within the host body. Hence, we believe that the designed in-silico vaccine could be helpful for experimentalists in the formulation of a highly effective vaccine for B. pseudomallei.

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