Ahmad Karkhah
Babol University of Medical Sciences, Iran
Title: In silico development of a peptide based vaccine inducing multi-epitope T-cell responses against hepatitis C virus
Biography
Biography: Ahmad Karkhah
Abstract
Background: Induction of a strong hepatitis C virus (HCV) specific T-helper 1 (Th1) T-cell response plays a pivotal role in control and clearance of the virus. A multi-epitope vaccine containing T-cell epitopes could be a promising vaccination strategy against HCV, but further computational evaluations are important before initiating the experimental study. Method: In the present study, we have employed various approaches to design an efficient multi-epitope vaccine. First, CD8+ cytolytic T-lymphocytes (CTLs) epitopes, helper epitopes and adjuvant which are three essential components of peptide vaccine were determined. CTL epitopes were selected from HCV genotype 1a/1b, consensus regions of non structural protein 3 (NS3) and non structural protein 4A (NS4A) by various servers. NS3 derived sequences by various servers were used to induce CD4+helper T-lymphocytes (HTLs) responses. Heparin-Binding Hemagglutinin (HBHA), a novel TLR4 agonist, was applied as an adjuvant to polarize CD4+T cells toward T-helper 1 to induce strong CTL responses. Then obtained epitopes were linked together by appropriate linkers to enhance epitope presentation. 3D model of protein was generated and physicochemical properties, stability and allergenicity of the protein were predicted using bioinformatics tools and servers. Results: Our results indicated that more than 90% residues locate in favorite or additional allowed region of Ramachandran Plot. Also, based on Ramachandran plot analysis this protein could be classified as a stable fusion protein. In addition, this multi-epitope protein had strong potential to induce specific T-cell response against HCV. Conclusion: Our results supported that this multi-antigenic vaccine could be effectively considered as an efficient vaccine for prophylactic or therapeutic usages.