Leveraging immunoinformatic for the rational design of highly immunogenic multi-epitope subunit vaccines against Dugbe virus: a molecular docking and simulation approach

The Dugbe virus is a tick-borne virus that poses a serious risk to cattle and human' health and belongs to the Orthonairovirus genus. Given the pressing public health threat posed by Dugbe virus infection and the absence of targeted vaccines or antiviral medications, the innovative immunoinformatic techniques were employed to design potent vaccine. The strategy of this study involves screening the envelopment polyprotein, Nucleoprotein, and RNA-dependent RNA polymerase to predict immunogenic HTL, CTL, and B cell epitopes. Predicted epitopes were modeled in 3D structure and validated for stability via molecular dynamics. Docking and immune simulations were used to asses vaccine-TLR3 interactions and immune response. To construct a multiepitope vaccine candidate, the chosen epitopes were linked together and subjected to 3D modeling. The molecular docking analysis confirmed the strong binding affinity between the constructed vaccine and human TLR8. Notably, a 500 ns molecular dynamics simulation further confirmed the robust stability and proper folding of the vaccine-TLR8 complex. The constructed vaccine demonstrated stable expression in the Escherichia coli host, benefiting from a codon adaptation index (CAI) of 1.0 and an average GC content of 50.74%, which falls within the optimal range of 30-70%. Furthermore, immune simulation analysis indicated an enhanced immune response characterized by increased levels of IgG, IgM, interleukins, and cytokines following vaccine injection. This study presents a computationally driven approach for designing a highly immunogenic multi-epitope subunit vaccine against the Dugbe virus, which warrants further experimental validation.