Cross-reactivity of hepatitis C virus specific vaccine-induced T cells at immunodominant epitopes.
Viral diversity is a challenge to the development of a hepatitis C virus (HCV) vaccine. Following vaccination of humans with adenoviral vectors, we determined the capacity of T cells to target common viral variants at immundominant epitopes ex vivo. We identified two major variants for epitopes NS3(...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2015
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| _version_ | 1797084679429423104 |
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| author | Kelly, C Swadling, L Brown, A Capone, S Folgori, A Salio, M Klenerman, P Barnes, E |
| author_facet | Kelly, C Swadling, L Brown, A Capone, S Folgori, A Salio, M Klenerman, P Barnes, E |
| author_sort | Kelly, C |
| collection | OXFORD |
| description | Viral diversity is a challenge to the development of a hepatitis C virus (HCV) vaccine. Following vaccination of humans with adenoviral vectors, we determined the capacity of T cells to target common viral variants at immundominant epitopes ex vivo. We identified two major variants for epitopes NS3(1073) and NS3(1446), and multiple variants for epitope NS3(1406) that occurred in >5% of genotype 1 and 3 sequences at a population level. Cross-reactivity of vaccine-induced T cells was determined using variant peptides in IFN-γ ELISPOT assays. Vaccine-induced T cells targeted approximately 90% of NS3(1073) genotype 1 sequences and 50% of NS3(1446) genotype 1 and 3 sequences. For NS3(1406), 62% of subtype-1b sequences were targeted. Next, we assessed whether an in vitro priming system, using dendritic cells and T cells from healthy donors, could identify a variant of NS3(1406) that was maximally cross-reactive. In vitro priming assays showed that of those tested the NS3(1406) vaccine variant was the most immunogenic. T cells primed with genotype 1 variants from subtype 1a or 1b were broadly cross-reactive with other variants from the same subtype. We conclude that immunization with candidate HCV adenoviral vaccines generates cross-reactive T cells at immunodominant epitopes. The degree of cross-reactivity varies between epitopes and may be HCV-subtype specific. |
| first_indexed | 2024-03-07T01:58:24Z |
| format | Journal article |
| id | oxford-uuid:9c85ec3a-43f9-4b2e-9716-349189fce287 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:58:24Z |
| publishDate | 2015 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:9c85ec3a-43f9-4b2e-9716-349189fce2872022-03-27T00:36:35ZCross-reactivity of hepatitis C virus specific vaccine-induced T cells at immunodominant epitopes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9c85ec3a-43f9-4b2e-9716-349189fce287EnglishSymplectic Elements at OxfordWiley2015Kelly, CSwadling, LBrown, ACapone, SFolgori, ASalio, MKlenerman, PBarnes, EViral diversity is a challenge to the development of a hepatitis C virus (HCV) vaccine. Following vaccination of humans with adenoviral vectors, we determined the capacity of T cells to target common viral variants at immundominant epitopes ex vivo. We identified two major variants for epitopes NS3(1073) and NS3(1446), and multiple variants for epitope NS3(1406) that occurred in >5% of genotype 1 and 3 sequences at a population level. Cross-reactivity of vaccine-induced T cells was determined using variant peptides in IFN-γ ELISPOT assays. Vaccine-induced T cells targeted approximately 90% of NS3(1073) genotype 1 sequences and 50% of NS3(1446) genotype 1 and 3 sequences. For NS3(1406), 62% of subtype-1b sequences were targeted. Next, we assessed whether an in vitro priming system, using dendritic cells and T cells from healthy donors, could identify a variant of NS3(1406) that was maximally cross-reactive. In vitro priming assays showed that of those tested the NS3(1406) vaccine variant was the most immunogenic. T cells primed with genotype 1 variants from subtype 1a or 1b were broadly cross-reactive with other variants from the same subtype. We conclude that immunization with candidate HCV adenoviral vaccines generates cross-reactive T cells at immunodominant epitopes. The degree of cross-reactivity varies between epitopes and may be HCV-subtype specific. |
| spellingShingle | Kelly, C Swadling, L Brown, A Capone, S Folgori, A Salio, M Klenerman, P Barnes, E Cross-reactivity of hepatitis C virus specific vaccine-induced T cells at immunodominant epitopes. |
| title | Cross-reactivity of hepatitis C virus specific vaccine-induced T cells at immunodominant epitopes. |
| title_full | Cross-reactivity of hepatitis C virus specific vaccine-induced T cells at immunodominant epitopes. |
| title_fullStr | Cross-reactivity of hepatitis C virus specific vaccine-induced T cells at immunodominant epitopes. |
| title_full_unstemmed | Cross-reactivity of hepatitis C virus specific vaccine-induced T cells at immunodominant epitopes. |
| title_short | Cross-reactivity of hepatitis C virus specific vaccine-induced T cells at immunodominant epitopes. |
| title_sort | cross reactivity of hepatitis c virus specific vaccine induced t cells at immunodominant epitopes |
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