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Journal of Virology, December 2002, p. 12735-12746, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12735-12746.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Comparative Vaccine Studies in HLA-A2.1-Transgenic Mice Reveal a Clustered Organization of Epitopes Presented in Hepatitis C Virus Natural Infection

Nourredine Himoudi,1 Jean-Daniel Abraham,2 Anne Fournillier,1 Yu Chun Lone,3 Aurélie Joubert,1 Anne Op De Beeck,4 Delphine Freida,1 François Lemonnier,3 Marie Paule Kieny,2 and Geneviève Inchauspé1*

Unité Mixte CNRS-BioMérieux, UMR 2142, Ecole Normale Supérieure, 69364 Lyon Cédex 07,1 INSERM U554, Institut de Virologie, 67000 Strasbourg,2 BÂtiment de Rétrovirologie, Institut Pasteur, 75015 Paris,3 CNRS-UPR2511, Institut de Biologie de Lille, 59021 Lille Cédex, France4

Received 28 May 2002/ Accepted 3 September 2002

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.

* Corresponding author. Mailing address: Unité Mixte CNRS-BioMérieux, UMR 2142, Ecole Normale Supérieure, 46 Allée d'Italie, 69364 Lyon Cédex 07, France. Phone: 33-44-72-72-85-90. Fax: 33-44-72-72-85-33. E-mail: genevieve.inchauspe{at}ens-lyon.fr.

Journal of Virology, December 2002, p. 12735-12746, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12735-12746.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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