Chimeric Vaccine Design against Melioidosis Via Subtractive Proteomics

Abstract

Multidrug-resistant Burkholderia pseudomallei is a significant global health concern associated with high morbidity and mortality rates. To address this issue, a chimeric multi-epitope vaccine against B. pseudomallei was designed using subtractive proteomics and reverse vaccinology. A subtractive proteomics strategy was applied to the 21 non-redundant proteomes of the pathogen. From these, proteins that were non-homologous to humans, essential for survival, and virulent were identified. BLASTp analysis against the PDB database and druggability assessments revealed nine proteins with available three-dimensional structures, of which four were deemed potential vaccine candidates based on subcellular localization and antigenicity predictions. Utilizing online tools, MHC class I, II, and B-cell epitopes were predicted and screened for toxicity, solubility, allergenicity, and hydrophilicity. Immunogenic epitopes were selected to construct a chimeric multi-epitope vaccine incorporating adjuvant, linker, and PADRE sequences. Molecular docking and dynamics simulations demonstrated strong interactions between the vaccine construct and HLA alleles and TLR4, indicating its potential to elicit a robust immune response. The availability of the B. pseudomallei proteome facilitated this study, demonstrating the effectiveness of insilico tools for identifying vaccine targets and designing chimeric vaccines using reverse vaccinology and immunoinformatics methodologies.