Development of polyepitopic immunogenic contrast against hepatitis C virus 1a-6a genotype by in silico approach

Abstract

Background: Hepatitis C is a viral disease associated with chronic hepatitis and hepatocellular carcinoma. Hepatitis C virus (HCV) plays a critical role in the pathogenesis of this disease. Nonstructural proteins including NS3, NS4A, and NS5A are important in viral replication and translation. Since recent therapies are not appropriate for anti-HCV activity in humans, the main objective of this study is the use of immunoinformatic approaches for designing a novel multiepitope peptide with antigenic properties and examining it as a vaccine against (1a-6a) genotypes of the virus. These types of studies can be helpful for the development of new vaccine strategies against hepatitis C disease. Methods: The conserved position of nonstructural proteins (NS3/NS4a and NS5A) of HCV genotypes was used for vaccine design. Linear and conformational epitopes of B cell, MHC-I, MHC-II binding epitopes, and interferon-gamma inducing epitopes were determined in the construction of the vaccine. Molecular dynamics (MD) simulation and protein docking multiepitope peptides with toll-like receptor (TLR) 3 and TLR8 were analyzed. Results: MD simulation revealed a stable structure of candidate vaccines. Hence, docking results showed multiepitope peptides interaction with TLR3 and TLR8 and epitopes related to NS3 protein have the most interaction. These analyses suggest that designed vaccines can induce humoral and cellular immune responses against HCV. Conclusions: These analyses suggest that designed vaccines can induce humoral and cellular immune responses against HCV. However, experimental tests are required to evaluate the safety and immunogenicity profile of designed multiepitope vaccines.