Formulation of a Novel NS5A- and NS5B-Based Chimeric Vaccine Against Hepatitis C Virus: An Artificial Intelligence-Supported Approach

Abstract

We aimed to design a multiepitope vaccine against hepatitis C virus (HCV) with the potential to elicit broad protective immunity against diverse HCV genotypes through computational design. Method : One hundred sequences of the most widespread subtypes of HCV were retrieved from the Los Alamos National Laboratory database, and consensus sequences of the NS5A and NS5B proteins were generated to construct an efficient vaccine for human use. Numerous B-cell lymphocyte, cytotoxic T-lymphocyte and helper T-lymphocyte epitopes located in the conserved domains of HCV proteins and similar in human and mouse alleles were evaluated criteria for use in the vaccine construct. Population coverage analysis identified that substantial parts of the worldwide population carry epitopes and their corresponding alleles within their genome, which confirms that the vaccine candidate is an effective agent against this lethal disease. Codon optimization and in silico cloning of eukaryotic and prokaryotic vectors validated the strong expression of the vaccine construct in the host systems. Molecular docking analysis revealed favorable binding affinities between the vaccine construct and toll-like receptors, which confirmed the vaccine’s capacity to induce robust and stable immune responses against the hepatitis C virus. We incorporated new bioinformatic methods to design multiepitope vaccine against HCV. The development of a vaccine targeting multi genotypes of HCV could potentially provide for long-term protection against infection and may mitigate the risk of drug resistance across various genotypes and subtypes. Current research emphasizes the need for a vaccine that can elicit comprehensive immune responses, including both neutralizing antibodies and T-cell responses, to effectively address the genetic diversity of the virus. Future experimental studies are essential to validate predicted immunogenicity, structural stability, and protective efficacy before clinical consideration.