Delineating blueprint of an epitope-based peptide vaccine against the multiple serovars of dengue virus: A hierarchical reverse vaccinology approach

摘要

Dengue is one of the most common life-threatening neglected tropical diseases of the world, therapeutics for whose treatment and prevention still remains undeveloped. Despite having been licensed, the existing vaccine (Dengvaxia) is rather inefficacious due to the presence of multiple serovars of the Dengue Virus (DENV). A dengue vaccine potent enough to work against all the serovars is very crucial, the development of which is time-intensive. Here, we have used a comprehensive hierarchical reverse vaccinology approach to design an epitope-based vaccine targeted against multiple serovars of the DENV. Conservancy and population coverage analysis of the predicted epitopes revealed robust immune response against multiple serovars of the DENV and various ethnicities of the human population. The final vaccine construct was designed by adding B and T-cell epitopes, Universal pan-HLA DR or PADRE (AKFVAAWTLKAAA) sequence, and an adjuvant (β-defensin) at the N-terminal with suitable linkers. Physiochemical properties and secondary structure profiling of the vaccine protein secured its hydrophilic, thermostable and other structural nature. Molecular docking analysis indicates the deep binding of the proposed vaccine in the binding groove of the human immune TLR4 receptor present on the dendritic cell. Additionally, disulfide engineering was performed to extend its stability. Furthermore, molecular dynamics simulation of the modeled vaccine-TLR4 complex showed minimum deformability. Finally,in silicocloning approach of the vaccine construct within an expression vector (pET28a+) was carried out to check translational potency and microbial expression. This proposed vaccine may provide a novel immunotherapeutic agent for dengue outbreak prevention and management.