Journal article
The broad assessment of HCV genotypes 1 and 3 antigenic targets reveals limited cross-reactivity with implications for vaccine design
Gut, Vol.65(1), pp.112-123
2016
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 IFNγ-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.
Details
- Title
- The broad assessment of HCV genotypes 1 and 3 antigenic targets reveals limited cross-reactivity with implications for vaccine design
- Authors/Creators
- A. von Delft (Author/Creator) - University of OxfordI.S. Humphreys (Author/Creator) - University of OxfordA. Brown (Author/Creator) - University of OxfordK. Pfafferott (Author/Creator) - University of OxfordM. Lucas (Author/Creator) - School of Pathology and Laboratory MedicineP. Klenerman (Author/Creator) - University of OxfordG.M. Lauer (Author/Creator) - Ragon Institute of MGH, MIT and HarvardA.L. Cox (Author/Creator) - John Hopkins Univ.S. Gaudieri (Author/Creator) - School of Anatomy, Physiology and Human BiologyE. Barnes (Author/Creator) - University of Oxford
- Publication Details
- Gut, Vol.65(1), pp.112-123
- Publisher
- BMJ Publishing Group
- Identifiers
- 991005542097907891
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.125 Hepatitis
- 1.125.83 HCV
- Web Of Science research areas
- Gastroenterology & Hepatology
- ESI research areas
- Clinical Medicine