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
Date Issued
01 August 2014
Access level
open access
Resource Type
journal article
Author(s)
Abdel-Hady K.
Terry F.
Desrosiers J.
De Groot A.
Azzazy H.
University of Rhode Island
Publisher(s)
Landes Bioscience
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.
Start page
2366
End page
2377
Volume
10
Issue
8
Language
English
OCDE Knowledge area
Gastroenterología, Hepatología
Scopus EID
2-s2.0-84908439506
PubMed ID
Source
Human Vaccines and Immunotherapeutics
ISSN of the container
21645515
Sponsor(s)
This work has been funded by a grant from the American University in Cairo to Dr Hassan Azzazy and an ARRA supplement to the U19 grant to Prof. Anne De Groot. The iVAX toolkit has been made available for academic use through a unique arrangement with the University of Rhode Island. Thanks to Sheila Chandran for assisting with the in silico analysis and Lana Abdel-Hady for assisting with the artwork
Sources of information: Directorio de Producción Científica Scopus