Designing of a novel and potential multi-epitope-based vaccine using NS5 protein of dengue virus targeting all serotypes from India: An immunoinformatic approach

Dengue, prevalent in over 100 countries, is caused by the four dengue virus serotypes. Despite efforts, no effective vaccine exists. This study uses immunoinformatics to develop a novel multi-epitope-based dengue vaccine using Non-structural 5 protein, known for its conservancy and ability to elicit strong T-cell response. After retrieving the sequences for all four serotypes from India, various parameters like antigenicity, allergenicity, and toxicity were analysed using VaxiJen and AllerTOPv. 2.0, and ToxinPred, respectively. All sequences were predicted to be antigenic, non-allergic, and non-toxic. The B and T-cell epitopes were predicted using ABCpred and IEDB, respectively. The epitopes were finalised for vaccine construction based on parameters like binding affinity, antigenicity, allergenicity, and immunogenicity. A total of 13 MHC-I and 11 MHC-II epitopes were selected. With the help of specific linkers, adjuvant, and PADRE sequences, the vaccine construct of 407 amino acids was constructed. It was further analysed for its antigenicity, allergenicity, and other physiochemical properties. The vaccine construct was predicted to be stable, antigenic, and non-allergenic. Further, secondary and tertiary structure prediction and refinement were also performed. Moreover, molecular docking and simulation of vaccine construct with human TLR-3 were done. Strong and stable interaction was observed with the immune receptors. Finally, in-silico cloning was performed, followed by immune simulation analysis. The vaccine construct induced strong B-cell and T-cell immune responses, the induction of other immune cells, and the production of interferons and interleukins. Finally, this study concluded that our predicted vaccine construct could be a potential and compelling candidate for all dengue virus serotypes.