Comparative vaccine studies in HLA-A2.1-transgenic mice reveal a clustered organization of epitopes presented in hepatitis C virus natural infection |
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| Authors: | Himoudi Nourredine Abraham Jean-Daniel Fournillier Anne Lone Yu Chun Joubert Aurélie Op De Beeck Anne Freida Delphine Lemonnier François Kieny Marie Paule Inchauspé Geneviève |
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| Affiliation: | Unité Mixte CNRS-BioMérieux, UMR 2142, Ecole Normale Supérieure, 46 Allée d'Italie, 69364 Lyon Cédex 07, France. |
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| 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. |
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