title: Strong vaccine-induced CD8 T-cell responses have cytolytic function in a chimpanzee clearing HCV infection.
abstract: A single correlate of effective vaccine protection against chronic HCV infection has yet to be defined. In this study, we analyzed T-cell responses in four chimpanzees, immunized with core-E1-E2-NS3 and subsequently infected with HCV1b. Viral clearance was observed in one animal, while the other three became chronically infected. In the animal that cleared infection, NS3-specific CD8 T-cell responses were observed to be more potent in terms of frequency and polyfunctionality of cytokine producing cells. Unique to this animal was the presence of killing-competent CD8 T-cells, specific for NS3 1258-1272, being presented by the chimpanzee MHC class I molecule Patr-A*03∶01, and a high affinity recognition of this epitope. In the animals that became chronically infected, T-cells were able to produce cytokines against the same peptide but no cytolysis could be detected. In conclusion, in the animal that was able to clear HCV infection not only cytokine production was observed but also cytolytic potential against specific MHC class I/peptide-combinations.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Babs E
authors.initials: BE
authors.lastname: Verstrepen
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Zahra C
authors.initials: ZC
authors.lastname: Fagrouch
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Mooij
authors.affiliation: Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Natasja G
authors.initials: NG
authors.lastname: de Groot
authors.affiliation: Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Bontrop
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Willy M
authors.initials: WM
authors.lastname: Bogers
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koopman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015870:Gene Expression; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007114:Immunization; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D014758:Viral Core Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D016207:Cytokines; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D014758:Viral Core Proteins; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
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