Comparative vaccine studies in HLA-A2.1-transgenic mice reveal a clustered organization of epitopes presented in hepatitis C virus natural infection.
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.
Himoudi
Nourredine
N
Unité Mixte CNRS-BioMérieux, UMR 2142, Ecole Normale Supérieure, 46 Allée d'Italie, 69364 Lyon Cédex 07, France.
Abraham
Jean-Daniel
JD
Fournillier
Anne
A
Lone
Yu Chun
YC
Joubert
Aurélie
A
Op De Beeck
Anne
A
Freida
Delphine
D
Lemonnier
François
F
Kieny
Marie Paule
MP
Inchauspé
Geneviève
G
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*
D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D019444:Vaccines, DNA; D014765:Viral Vaccines; D007371:Interferon-gamma