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Comparative vaccine studies in HLA-A2.1-transgenic mice reveal a clustered organization of epitopes presented in hepatitis C virus natural infection.

par 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
Référence Journal of virology, 76, 24, page (12735-12746)
Publication Publié, 2002-12

Article révisé par les pairs

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Résumé :

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.