A novel multi-epitope peptide vaccine against (a) genotype of Hepatitis C virus: An in silico approach

Background and Objectives: Hepatitis C is a virus disease causes chronic hepatitis and carcinoma hepatocellular. Non-structural proteins NS3, NS4A and NS5A are important in virus replication and translation. Recent therapies are not appropriate for anti-hepatitis C virus activity in human. In this study, due to the frequency of 1a and 3a subtypes of HCV in Iran a fusion protein has designed using bioinformatics techniques based on non-structural proteins NS3, NS4 and NS5A. Predicted immunogenicity properties of designed fusion protein can be used as a multi-epitope vaccine for genotype (a) to prevent hepatitis C disease. Materials and Methods: In order to design the vaccine, conserved sequence of proteins (NS3/NS4A and NS5A) of (a) genotype HCV are used. All epitopes including Linear and conformational B cell, MHC-I and MHC-II binding epitopes and inducing Gamma interferon epitopes were determined in vaccine construct. Also, similar motifs detected by MHC-I, MHC-II, B cell and Gamma interferon Linked by the GGGS linker. 3D-structure and Molecular dynamics (MD) simulation of designed peptide determined by ITASSER and GROMACS package. Molecular docking was performed between TLR-3 and TLR-8 immune receptors using Cluspro server. To analysis the schematic illustration of the interactions between docked proteins the PDBsum online database was used. Results: The final designed multi-epitope protein includes 170 amino acids. The structure of protein composed of 18.2% Helix, 9.4% sheet, 14.1% Turn and 58.2% coil. Molecular dynamics (MD) simulation revealed stable structure of candidate vaccines. So, the best model docking with the most clusters and the lowest energy was selected. Docking results showed multi-epitope peptide interacted with Toll-like 3 and 8 receptors. Conclusion: These analyses suggest designed vaccines can induced humoral and cellular immune responses against HCV. However, experimental tests are required to evaluate the safety and immunogenicity profile of designed multi-epitope vaccines.