Analysis of Promiscuous T cell Epitopes for Vaccine Development Against West Nile Virus Using Bioinformatics Approaches

Abstract

West Nile virus (WNV) is a major pathogenic flavivirus which causes human neuro-invasive disease, worldwide. Still successful vaccine and therapeutic treatment against WNV infection is not available, which demands the development of more potential WNV vaccines. The present study used immunoinformatics methods viz. Matrix and Artificial Neural Network (ANN) based algorithm to identify the promiscuous and conserve T cell epitopes from entire WNV proteome followed by structure based analysis of identified epitopes. The epitopes were also taken for TAP binding analysis and epitope conservancy analysis. Among 89 identified epitopes, eight epitopes showed high potential and conserve nature but two epitopes viz. capsid 40FVLALLAFF48 and NS2B 9LMFAIVGGL17 were found most promiscuous and having high population coverage in comparison of other identified epitopes and known antigenic positive control epitopes. Further, Autodock 4.2 and NAMD–VMD molecular dynamics simulation were used for docking and molecular dynamics simulation respectively, to validate epitope and allele complex stability. The 3D structure models were generated for epitopes and corresponding HLA allele by Pepstr and Modeller 9.10, respectively. Epitope FVLALLAFF-B*3501 allele and epitope LMFAIVGGL-B*5101 HLA allele complexes have shown best energy minimization and stable complexes during simulation. The study also showed the optimum binding epitopes FVLALLAFF and LMFAIVGGL with cTAP1 (PDB ID: 1JJ7) cavity, as revealed by Autodock 4.2, concluding favored passage through the ER membrane from cytosol to the ER lumen during cytosolic processing. The docking experiment of epitopes FVLALLAFF, LMFAIVGGL with cTAP1 very well show 1 H-bond state with a binding energy of −1.62 and −0.23 kcal/mol, respectively. These results show a smooth pass through of the epitope across the channel of cTAP1 via being weakly bonded and released into the ER lumen through the cavity of cTAP1. Overall, identified peptides have potential application in the development of short peptide based vaccines and diagnostic agents for West Nile virus.