dc.creator | Fytili, P. | en |
dc.creator | Dalekos, G. N. | en |
dc.creator | Schlaphoff, V. | en |
dc.creator | Suneetha, P. V. | en |
dc.creator | Sarrazin, C. | en |
dc.creator | Zauner, W. | en |
dc.creator | Zachou, K. | en |
dc.creator | Berg, T. | en |
dc.creator | Manns, M. P. | en |
dc.creator | Klade, C. S. | en |
dc.creator | Cornberg, M. | en |
dc.creator | Wedemeyer, H. | en |
dc.date.accessioned | 2015-11-23T10:26:51Z | |
dc.date.available | 2015-11-23T10:26:51Z | |
dc.date.issued | 2008 | |
dc.identifier | 10.1016/j.vaccine.2008.05.045 | |
dc.identifier.issn | 0264-410X | |
dc.identifier.uri | http://hdl.handle.net/11615/27607 | |
dc.description.abstract | The HCV-specific HLA-A2-restricted NS3(1073) epitope is one of the most frequently recognized epitopes in hepatitis C. NS3(1073)-specific T-cell responses are associated with clearance of acute HCV-infection. Therefore this epitope is an interesting candidate for a HCV-peptide vaccine. However, heterogeneity between genotypes and mutations in the epitope has to be considered as an obstacle. We here identified 34 naturally occurring NS3(1073)-variants, as compared with the wild type genotype-1 variants (CVNGVCWTV/CINGVCWTV) by sequencing sera of 251 Greek and German patients and searching for published HCV-genomes. The frequency of variants among genotype-1 patients was 10%. Importantly, HLA-A2 binding was reduced only in 3 genotype 1 mutants while all non-genotype I variants showed strong HLA-A2-binding. By screening 28 variants in ELISPOT assays from T cell lines we could demonstrate that HCV-NS3(1073)-wild-type-specific T-cells displayed cross-genotype-reactivity, in particular against genotypes 4-6 variants. However, single aa changes within the TCR-binding domain completely abolished recognition even in case of conservative aa exchanges within genotype-1. NS3(1073)-specific T-cell lines from recovered, chronically infected, and HCV-negative individuals showed no major difference in the pattern of cross-recognition although the proliferation of NS3(1073)-specific T-cells differed significantly between the groups. Importantly, the recognition pattern against the 28 variants was also identical directly ex vivo in a patient with acute HCV infection and a healthy volunteer vaccinated with the peptide vaccine IC41 containing the NS3(1073)-wild-type peptide. Thus, partial cross-genotype recognition of HCV NS3(1073)-specific CD8 T cells is possible; however, even single aa exchanges can significantly limit the potential efficacy of vaccines containing the NS3(1073)-wildtype peptide. (C) 2008 Elsevier Ltd. All rights reserved. | en |
dc.source | Vaccine | en |
dc.source.uri | <Go to ISI>://WOS:000258009000006 | |
dc.subject | hepatitis C | en |
dc.subject | peptide vaccine | en |
dc.subject | CD8+T-cell | en |
dc.subject | cross-genotype recognition | en |
dc.subject | NS3 1073 | en |
dc.subject | epitope variants | en |
dc.subject | HEPATITIS-C-VIRUS | en |
dc.subject | IMMUNE-RESPONSES | en |
dc.subject | PEPTIDE-VACCINE | en |
dc.subject | VIRAL CLEARANCE | en |
dc.subject | INFECTION | en |
dc.subject | IMMUNOGENICITY | en |
dc.subject | INDIVIDUALS | en |
dc.subject | REPLICATION | en |
dc.subject | PERSISTENCE | en |
dc.subject | RECHALLENGE | en |
dc.subject | Immunology | en |
dc.subject | Medicine, Research & Experimental | en |
dc.title | Cross-genotype-reactivity of the immunodominant HCVCD8 T-cell epitope NS3-1073 | en |
dc.type | journalArticle | en |