{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:10:17Z","timestamp":1785175817027,"version":"3.55.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Induction of functional helper CD4<jats:sup>+<\/jats:sup> T cells is the hallmark of a protective immune response against hepatitis C virus (HCV), associated with spontaneous viral clearance. Heterologous prime\/boost viral vectored vaccination has demonstrated induction of broad and polyfunctional HCV\u2010specific CD8<jats:sup>+<\/jats:sup> T cells in healthy volunteers; however, much less is known about CD4<jats:sup>+<\/jats:sup> T\u2010cell subsets following vaccination.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We analyzed HCV\u2010specific CD4<jats:sup>+<\/jats:sup> T\u2010cell populations using major histocompatibility complex class II tetramers in volunteers undergoing HCV vaccination with recombinant HCV adenoviral\/modified vaccinia Ankara viral vectors. Peptide\u2010specific T\u2010cell responses were tracked over time, and functional (proliferation and cytokine secretion) and phenotypic (cell surface and intranuclear) markers were assessed using flow cytometry. These were compared to CD4<jats:sup>+<\/jats:sup> responses in 10 human leukocyte antigen\u2013matched persons with HCV spontaneous resolution and 21 chronically infected patients treated with directly acting antiviral (DAA) therapy. Vaccination induced tetramer\u2010positive CD4<jats:sup>+<\/jats:sup> T cells that were highest 1\u20104 weeks after boosting (mean, 0.06%). Similar frequencies were obtained for those tracked following spontaneous resolution of disease (mean, 0.04%). In addition, the cell\u2010surface phenotype (CD28, CD127) memory subset markers and intranuclear transcription factors, as well as functional capacity of peptide\u2010specific CD4<jats:sup>+<\/jats:sup> T\u2010cell responses characterized after vaccination, are comparable to those following spontaneous viral resolution. In contrast, helper responses in chronic infection were infrequently detected and poorly functional and did not consistently recover following HCV cure.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Helper CD4<jats:sup>+<\/jats:sup> T\u2010cell phenotype and function following HCV viral vectored vaccination resembles \u201cprotective memory\u201d that is observed following spontaneous clearance of HCV. DAA cure does not promote resurrection of exhausted CD4<jats:sup>+<\/jats:sup> T\u2010cell memory in chronic infection.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31160","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T18:54:58Z","timestamp":1580756098000},"page":"1541-1555","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":19,"title":["Characterizing Hepatitis C Virus\u2013Specific CD4+ T Cells Following Viral\u2010Vectored Vaccination, Directly Acting Antivirals, and Spontaneous Viral Cure"],"prefix":"10.1097","volume":"72","author":[{"given":"Felicity","family":"Hartnell","sequence":"first","affiliation":[{"name":"Peter Medawar Building for Pathogen Research,University of Oxford,Oxford,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Esposito","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen 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Srl,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Barnes","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research,University of Oxford,Oxford,United Kingdom"},{"name":"Jenner Vaccine Trials,Nuffield Department of Medicine,University of Oxford,Oxford,United Kingdom"},{"name":"NIHR Biomedical Research Centre Oxford,John Radcliffe Hospital,Oxford,United Kingdom"},{"name":"Translational Gastroenterology Unit,John Radcliffe Hospital,Oxford,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research,University of Oxford,Oxford,United Kingdom"},{"name":"Jenner Vaccine Trials,Nuffield Department of Medicine,University of Oxford,Oxford,United Kingdom"},{"name":"NIHR Biomedical Research Centre Oxford,John Radcliffe Hospital,Oxford,United Kingdom"},{"name":"Translational 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