Whipple's disease is caused by T. whipplei, a Gram-positive pathogenic bacterium. It is considered a
persistent infection affecting various organs, more likely to infect males. There is currently no licensed vaccination available for
Whipple's disease; thus, the development of a chimeric
peptide-based
vaccine against T. whipplei has the potential to be tremendously beneficial in preventing
Whipple's disease in the future. The present study aimed to apply modern computational approaches to generate a multi-
epitope-based
vaccine that expresses
antigenic determinants prioritized from the core
proteome of two T. whipplei whole
proteomes. Using an integrated computational approach, four
immunodominant epitopes were found from two extracellular
proteins. Combined, these
epitopes covered 89.03% of the global population. The shortlisted
epitopes exhibited a strong binding affinity for the B- and T-cell reference set of alleles, high antigenicity score, nonallergenic nature, high solubility, nontoxicity, and excellent binders of DRB1*0101. Through the use of appropriate linkers and adjuvation with a suitable adjuvant molecule, the
epitopes were designed into a chimeric
vaccine. An adjuvant was linked to the connected
epitopes to boost immunogenicity and efficiently engage both innate and adaptive immunity. The physiochemical properties of the
vaccine were observed favorable, leading toward the 3D modeling of the construct. Furthermore, the
vaccine's binding confirmation to the TLR-4 critical innate immune receptor was also determined using molecular docking and molecular dynamics (MD) simulations, which shows that the
vaccine has a strong binding affinity for TLR4 (-29.4452 kcal/mol in MM-GBSA and -42.3229 kcal/mol in MM-
PBSA). Overall, the
vaccine described here has a promising potential for eliciting protective and targeted immunogenicity, subject to further experimental testing.