title: Comparative vaccine studies in HLA-A2.1-transgenic mice reveal a clustered organization of epitopes presented in hepatitis C virus natural infection.
abstract: A polyepitopic CD8(+)-T-cell response is thought to be critical for control of hepatitis C virus (HCV) infection. Using transgenic mice, we analyzed the immunogenicity and dominance of most known HLA-A2.1 epitopes presented during infection by using vaccines that carry the potential to enter clinical trials: peptides, DNA, and recombinant adenoviruses. The vaccines capacity to induce specific cytotoxic T lymphocytes and interferon gamma-producing cells revealed that immunogenic epitopes are clustered in specific antigens. For two key antigens, flanking regions were shown to greatly enhance the scope of epitope recognition, whereas a DNA-adenovirus prime-boost vaccination strategy augmented epitope immunogenicity, even that of subdominant ones. The present study reveals a clustered organization of HCV immunogenic HLA.A2.1 epitopes and strategies to modulate their dominance.
authors.affiliation: Unité Mixte CNRS-BioMérieux, UMR 2142, Ecole Normale Supérieure, 46 Allée d'Italie, 69364 Lyon Cédex 07, France.
authors.forename: Nourredine
authors.initials: N
authors.lastname: Himoudi
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Abraham
authors.forename: Anne
authors.initials: A
authors.lastname: Fournillier
authors.forename: Yu Chun
authors.initials: YC
authors.lastname: Lone
authors.forename: Aurélie
authors.initials: A
authors.lastname: Joubert
authors.forename: Anne
authors.initials: A
authors.lastname: Op De Beeck
authors.forename: Delphine
authors.initials: D
authors.lastname: Freida
authors.forename: François
authors.initials: F
authors.lastname: Lemonnier
authors.forename: Marie Paule
authors.initials: MP
authors.lastname: Kieny
authors.forename: Geneviève
authors.initials: G
authors.lastname: Inchauspé
mesh_terms: D000818:Animals; D015789:HLA-A2 Antigen / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D007114:Immunization; D016056:Immunodominant Epitopes; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D019444:Vaccines, DNA; D014765:Viral Vaccines; D007371:Interferon-gamma