Sequence and Structure Based Binding Prediction Study of HLA Class I and cTAP Binding Peptides for Japanese Encephalitis Vaccine Development

Japanese encephalitis is a major threat in developing countries, even the availability of several conventional vaccines, which demand development of more effective vaccines. The present study used propred I and Immune Epitope Database Artificial Neural Network (ANN) algorithm (IEDB-ANN) to identify the conserve and promiscuous T cell epitopes from JEV proteome followed by structure based analysis of potential epitopes. Among all identified 102 epitopes, ten epitope were promiscuous but two epitopes of glycoprotein viz. (55)LVTVNPFVA(63) and (38)IPIVSVASL(46) were found most promiscuous, highly conserved and high population coverage in comparison of known antigenic positive control peptides. The B cell epitopes of glycoprotein also share these two T cell epitopes revealed by BCPred algorithm which can be a basis to confer the protection by neutralizing antibody combined with an effective cell-mediated response. 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 binding stability. The 3D structure models were generated for epitopes and corresponding HLA allele by Pepstr and Modeller 9.10 respectively. Epitope LVTVNPFVA-B5101 allele complex showed best energy minimization and stability over the time window during simulation. Here we also present the binding sequel of epitope LVTVNPFVA and its eventual transport through cTAP1 (PDB ID: 1JJ7) revealed by Autodock 4.2, which is an essential path for HLA class I binding epitopes to elicit immune response. The docking experiment of epitope LVTVNPFVA and cTAP1 very well show a 2 H-bond with a binding energy of -1.88 kcal/mol and other binding state of epitope forming no H-bond with a binding energy of -1.13 kcal/mol in the lower area of cTAP1 cavity. These results show a smooth pass through of the epitope across the channel of cTAP1. Overall, identified peptides have potential application in the design and development of short peptide based vaccines and diagnostic agents for Japanese encephalitis.