{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:22:04Z","timestamp":1778768524269,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T00:00:00Z","timestamp":1414627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K010239\/1"],"award-info":[{"award-number":["MR\/K010239\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>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<jats:sub>1073<\/jats:sub> and NS3<jats:sub>1446<\/jats:sub>, and multiple variants for epitope NS3<jats:sub>1406<\/jats:sub> that occurred in &gt;5% of genotype 1 and 3 sequences at a population level. Cross\u2010reactivity of vaccine\u2010induced T cells was determined using variant peptides in IFN\u2010\u03b3 ELISPOT assays. Vaccine\u2010induced T cells targeted approximately 90% of NS3<jats:sub>1073<\/jats:sub> genotype 1 sequences and 50% of NS3<jats:sub>1446<\/jats:sub> genotype 1 and 3 sequences. For NS3<jats:sub>1406,<\/jats:sub> 62% of subtype\u20101b 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<jats:sub>1406<\/jats:sub> that was maximally cross\u2010reactive. In vitro priming assays showed that of those tested the NS3<jats:sub>1406<\/jats:sub> vaccine variant was the most immunogenic. T cells primed with genotype 1 variants from subtype 1a or 1b were broadly cross\u2010reactive with other variants from the same subtype. We conclude that immunization with candidate HCV adenoviral vaccines generates cross\u2010reactive T cells at immunodominant epitopes. The degree of cross\u2010reactivity varies between epitopes and may be HCV\u2010subtype specific.<\/jats:p>","DOI":"10.1002\/eji.201444686","type":"journal-article","created":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T09:39:35Z","timestamp":1411810775000},"page":"309-316","source":"Crossref","is-referenced-by-count":32,"title":["Cross\u2010reactivity of hepatitis C virus specific vaccine\u2010induced T cells at immunodominant epitopes"],"prefix":"10.1002","volume":"45","author":[{"given":"Christabel","family":"Kelly","sequence":"first","affiliation":[{"name":"Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo","family":"Swadling","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Brown","sequence":"additional","affiliation":[{"name":"Nuffield Department 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