The broad assessment of HCV genotypes 1 and 3 antigenic targets reveals limited cross-reactivity with implications for vaccine design.
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...
| Päätekijät: | , , , , , , , , , |
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| Aineistotyyppi: | Journal article |
| Kieli: | English |
| Julkaistu: |
2015
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| _version_ | 1826297369503727616 |
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| author | von Delft, A Humphreys, I Brown, A Pfafferott, K Lucas, M Klenerman, P Lauer, G Cox, A Gaudieri, S Barnes, E |
| author_facet | von Delft, A Humphreys, I Brown, A Pfafferott, K Lucas, M Klenerman, P Lauer, G Cox, A Gaudieri, S Barnes, E |
| author_sort | von Delft, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T04:30:33Z |
| format | Journal article |
| id | oxford-uuid:ce26884d-740b-4c69-adb6-d8bff173d6c7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:30:33Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | oxford-uuid:ce26884d-740b-4c69-adb6-d8bff173d6c72022-03-27T07:33:49ZThe broad assessment of HCV genotypes 1 and 3 antigenic targets reveals limited cross-reactivity with implications for vaccine design.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ce26884d-740b-4c69-adb6-d8bff173d6c7EnglishSymplectic Elements at Oxford2015von Delft, AHumphreys, IBrown, APfafferott, KLucas, MKlenerman, PLauer, GCox, AGaudieri, SBarnes, EOBJECTIVE: 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. |
| spellingShingle | von Delft, A Humphreys, I Brown, A Pfafferott, K Lucas, M Klenerman, P Lauer, G Cox, A Gaudieri, S Barnes, E The broad assessment of HCV genotypes 1 and 3 antigenic targets reveals limited cross-reactivity with implications for vaccine design. |
| title | The broad assessment of HCV genotypes 1 and 3 antigenic targets reveals limited cross-reactivity with implications for vaccine design. |
| title_full | The broad assessment of HCV genotypes 1 and 3 antigenic targets reveals limited cross-reactivity with implications for vaccine design. |
| title_fullStr | The broad assessment of HCV genotypes 1 and 3 antigenic targets reveals limited cross-reactivity with implications for vaccine design. |
| title_full_unstemmed | The broad assessment of HCV genotypes 1 and 3 antigenic targets reveals limited cross-reactivity with implications for vaccine design. |
| title_short | The broad assessment of HCV genotypes 1 and 3 antigenic targets reveals limited cross-reactivity with implications for vaccine design. |
| title_sort | broad assessment of hcv genotypes 1 and 3 antigenic targets reveals limited cross reactivity with implications for vaccine design |
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