title: Identification and retrospective validation of T-cell epitopes in the hepatitis C virus genotype 4 proteome: an accelerated approach toward epitope-driven vaccine development.
abstract: With over 150 million people chronically infected worldwide and millions more infected annually, hepatitis C continues to pose a burden on the global healthcare system. The standard therapy of hepatitis C remains expensive, with severe associated side effects and inconsistent cure rates. Vaccine development against the hepatitis C virus has been hampered by practical and biological challenges posed by viral evasion mechanisms. Despite these challenges, HCV vaccine research has presented a number of candidate vaccines that progressed to phase II trials. However, those efforts focused mainly on HCV genotypes 1 and 2 as vaccine targets and barely enough attention was given to genotype 4, the variant most prevalent in the Middle East and central Africa. We describe herein the in silico identification of highly conserved and immunogenic T-cell epitopes from the HCV genotype 4 proteome, using the iVAX immunoinformatics toolkit, as targets for an epitope-driven vaccine. We also describe a fast and inexpensive approach for results validation using the empirical data on the Immune Epitope Database (IEDB) as a reference. Our analysis identified 90 HLA class I epitopes of which 20 were found to be novel and 19 more had their binding predictions retrospectively validated; empirical data for the remaining 51 epitopes was insufficient to validate their binding predictions. Our analysis also identified 14 HLA class II epitopes, of which 8 had most of their binding predictions validated. Further investigation is required regarding the efficacy of the identified epitopes as vaccine targets in populations where HCV genotype 4 is most prevalent.
authors.affiliation: a Department of Chemistry; School of Sciences and Engineering; The American University in Cairo; New Cairo, Egypt.
authors.forename: Karim M
authors.initials: KM
authors.lastname: Abdel-Hady
authors.forename: Andres H
authors.initials: AH
authors.lastname: Gutierrez
authors.forename: Frances
authors.initials: F
authors.lastname: Terry
authors.forename: Joe
authors.initials: J
authors.lastname: Desrosiers
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
authors.forename: Hassan M E
authors.initials: HM
authors.lastname: Azzazy
mesh_terms: D000350:Africa, Central / Q000453:epidemiology; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006526:Hepatitis C / Q000453:epidemiology / Q000821:virology; D006801:Humans; D008877:Middle East / Q000453:epidemiology; D020543:Proteome / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D020543:Proteome; D014764:Viral Proteins
keywords: Immune Epitope Database; T-cell epitopes; genotype 4; hepatitis C virus; immunoinformatics; vaccine; validation