Designing potent and immunogenic epitope based peptide vaccine against all serotypes of DENV via structural, physico-chemical and immunoinformatics-based approaches.

The globally severe dengue infection caused by all four dengue virus serotypes continues to be a major public health burden. Thus, the present study aimed to design an epitope based peptide vaccine against the E protein using an immunoinformatic approach. Although there is a licensed vaccine against dengue, its efficacy varies across serotypes. We designed an epitope based vaccine against the E protein of dengue that is effective for all serotypes via rigorous computational screening. Immunoinformatic approaches have been used for identifying active domains and functional pockets of the DENV E protein, followed by epitope prediction, model generation, physico-chemical characterization, antigenicity, allergenicity, toxicity analysis. After screening, epitopes within the 45-65 amino acid range were considered to design the vaccine construct. Our final vaccine construct is highly antigenic (0.7991), non-allergenic, and non-toxic. Molecular docking and molecular dynamics simulations further confirmed the stability and high binding energy of the vaccine construct with TLR2 (ΔG = -13.9 kcal/mol), TLR3 (ΔG = -12.4 kcal/mol), human IgG heavy chain (ΔG = -11.7 kcal/mol, and light chain (ΔG = -11.3 kcal/mol). In silico immune simulations showed enhanced B-cell and T-cell responses. In silico cloning and codon optimization confirmed efficient translation of the vaccine construct and its successful expression in the Escherichia coli host system (E. coli K12 strain). However, in vitro and in vivo validations are required to confirm the above-mentioned computational results for the promotion of the vaccine efficacy process.