Sequence and Structure Based Binding Prediction Study of HLA Class I and cTAP Binding Peptides for Japanese Encephalitis Vaccine Development
- 99 Downloads
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. 55LVTVNPFVA63 and 38IPIVSVASL46 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.
KeywordscTAP Epitope Encephalitis Immunoinformatics Simulation Vaccine
We are thankful to Prof. A. K. Ghosh, IFTM University, for his experimental guidance during the course of experimental work. We are also grateful to Institute of Engineering and Technology, Mangalayatan University, for providing necessary experimental facilities.
Compliance of Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
The authors declare that there were no animals or humans involved in this present study.
- Burrows SR, Elkington RA, Miles JJ, Green KJ, Walker S, Haryana SM, Moss DJ, Dunckley H, Burrows JM, Khanna R (2003) Promiscuous CTL recognition of viral epitopes on multiple human leukocyte antigens: biological validation of the proposed HLA A24 supertype. J Immunol 171:1407–1412CrossRefPubMedGoogle Scholar
- Castelli M, Cappelletti F, Diotti RA, Sautto G, Criscuolo E, Peraro MD, Clementi N (2013) Peptide-Based vaccinology: experimental and computational approaches to target hypervariable viruses through the fine characterization of protective epitopes recognized by monoclonal antibodies and the identification of T-cell-activating peptides. Clin Dev Immunol. doi: 10.1155/2013/521231 PubMedPubMedCentralGoogle Scholar
- Erra EO, Askling HH, Rombo L, Riutta J, Vene S, Yoksan S, Lindquist L, Pakkanen SH, Huhtamo E, Vapalahti O, Kantele A (2012) A single dose of vero cell-derived Japanese encephalitis (JE) vaccine (Ixiaro) effectively boosts immunity in travelers primed with mouse brain-derived JE vaccines. Clin Infect Dis 55:825–834CrossRefPubMedPubMedCentralGoogle Scholar
- Feng G, Jiang Q, Xia M, Lu Y, Qiu W, Zhao D, Lu L, Peng G, Wang Y (2013) Enhanced immune response and protective effects of Nano-chitosan-based DNA vaccine encoding T Cell epitopes of Esat-6 and FL against Mycobacterium tuberculosis infection. PLoS One 8(4):e61135CrossRefPubMedPubMedCentralGoogle Scholar
- Jardine J, Julien JP, Menis S, Ota T, Kalyuzhniy O, McGuire A, Sok D, Huang PS, MacPherson S, Jones M, Nieusma T, Mathison J, Baker D, Ward AB, Burton DR, Stamatatos L, Nemazee D, Wilson IA, Schief WR (2013) Rational HIV immunogen design to target specific germline B cell receptors. Science 340(6133):711–716CrossRefPubMedPubMedCentralGoogle Scholar
- Singh A, Mitra M, Sampath G, Venugopal P, Rao JV, Krishnamurthy B, Gupta MK, Sri Krishna S, Sudhakar B, Rao NB, Kaushik Y, Gopinathan K, Hegde NR, Gore MM, Krishna Mohan V, Ella KM (2015a) A Japanese encephalitis vaccine from India induces durable and cross-protective immunity against temporally and spatially wide-ranging global field strains. J Infect Dis 212(5):715–725CrossRefPubMedGoogle Scholar
- WHO (2015) Weekly epidemiological record. WHO, Geneva, pp 69–88Google Scholar