Selection of Conserved Epitopes from Hepatitis C Virus for Pan-Populational Stimulation of T-Cell Responses

Abstract

The hepatitis C virus (HCV) is able to persist as a chronic infection, which can lead to cirrhosis and liver cancer. There is evidence that clearance of HCV is linked to strong responses by CD8 cytotoxic T lymphocytes (CTLs), suggesting that eliciting CTL responses against HCV through an epitope-based vaccine could prove an effective means of immunization. However, HCV genomic plasticity as well as the polymorphisms of HLA I molecules restricting CD8 T-cell responses challenges the selection of epitopes for a widely protective vaccine. Here, we devised an approach to overcome these limitations. From available databases, we first collected a set of 245 HCV-specific CD8 T-cell epitopes, all known to be targeted in the course of a natural infection in humans. After a sequence variability analysis, we next identified 17 highly invariant epitopes. Subsequently, we predicted the epitope HLA I binding profiles that determine their potential presentation and recognition. Finally, using the relevant HLA I-genetic frequencies, we identified various epitope subsets encompassing 6 conserved HCV-specific CTL epitopes each predicted to elicit an effective T-cell response in any individual regardless of their HLA I background. We implemented this epitope selection approach for free public use at the EPISOPT web server.

Immunogenicity Prediction by VaxiJen: A Ten Year Overview

“…Such efforts fall into two camps: un-validated prediction-only methods that predict supposedly high-binding and more modern approaches that use immunoinformatics to select rather than predict the best epitopes suitable for forming a vaccine [204,205]; Helping to identify immunogenic and potentially protective single proteins from the genome of a given pathogenic microorganism. Such methodologies come in two main guises: "pipelines" or networks of methods and algorithms that together are able to select appropriate proteins [206,207] and single methods that seek to predict immunogens.…”

iVAX: An integrated toolkit for the selection and optimization of antigens and the design of epitope-driven vaccines

“…For instance, although some viruses exhibit a high degree of strain-to-strain variation at the protein level, highly conserved, immunogenic T cell epitopes can be identified using computational methods; examples can be found in preclinical studies related to tuberculosis (TB), Human Immunodeficiency Virus (HIV), smallpox and H. pylori published by our group [9][10][11][12][13][14][15][16] and in those published by other geneto-vaccine researchers (Sette and Newman, 17 Brusic, 18 Petrovsky, 19 Reche, 20 and He, 21 for example). Vaccines that include multiple epitopes in a single delivery vehicle have been shown to elicit epitope-specific, broad-based immune response, conferring protection against several strains.…”

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production

“…43 By contrast, allele-based selection methods define promiscuous epitopes as those restricted to as many HLA alleles as possible in the target population, as a function of specific allele frequency distributions. These methods includes OptiTope, 44 Episopt, 45 and Predivac-2.0. 21 In addition, some algorithms have been proposed to simultaneously optimize coverage of HLA alleles (target population) and pathogen antigenic coverage.…”