Detail The broad assessment of HCV genotypes 1 and 3 antigenic targets reveals limited cross-reactivity with implications for vaccine design (from Gut 2016, 65, 112-123) Bibliografi Author: Delft, Annette von ; Humphreys, Isla S. ; Brown, Anthony ; Pfafferott, Katja ; Lucas, Michaela ; Klenerman, Paul ; Lauer, Georg M. ; Cox, Andrea L. ; Gaudieri, Silvana ; Barnes, Eleanor Topik: HCV; Hepatitis C; Vaccine design; Validation ref - 31 Bahasa: (EN )     Tahun Terbit: 2016     Jenis: Article - diterbitkan di jurnal ilmiah internasional Fulltext: gutjnl-2014-308724.pdf (1.66MB; 0 download) [Informasi yang berkaitan dengan koleksi ini di internet] Abstract Objective: Developing a vaccine that is cross-reactive between HCV genotypes requires data on T cell antigenic targets that extends beyond genotype-1. We characterised T cell immune responses against HCV genotype-3, the most common infecting genotype in the UK and Asia, and assessed within genotype and between genotype cross-reactivity. Design: T cell targets were identified in 140 subjects with either acute, chronic or spontaneously resolved HCV genotype-3 infection using (1) overlapping peptides and (2) putative human leucocyte antigens (HLA)-class-I wild type and variant epitopes through the prior assessment of polymorphic HCV genomic sites associated with host HLA, in IFN?-ELISpot assays. CD4 +/CD8+ T cell subsets were defined and viral variability at T cell targets was determined through population analysis and viral sequencing. T cell cross-reactivity between genotype-1 and genotype-3 variants was assessed. Results: In resolved genotype-3 infection, T cells preferentially targeted non-structural proteins at a high magnitude, whereas in chronic disease T cells were absent or skewed to target structural proteins. Additional responses to wild type but not variant HLA predicted peptides were defined. Major sequence viral variability was observed within genotype-3 and between genotypes 1 and 3 HCV at T cell targets in resolved infection and at dominant epitopes, with limited T cell cross-reactivity between viral variants. Overall 41 CD4/CD8+ genotype-3 T cell targets were identified with minimal overlap with those described for HCV genotype-1. Conclusions: HCV T cell specificity is distinct between genotypes with limited T cell cross-reactivity in resolved and chronic disease. Therefore, viral regions targeted in natural HCV infection may not serve as attractive targets for a vaccine that aims to protect against multiple HCV genotypes. [validation ref - 31] Opini Anda Klik untuk menuliskan opini Anda tentang koleksi ini! Lihat Sejarah Pengadaan  Konversi Metadata   Kembali

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