| Domaine : |
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Sciences du Vivant/Microbiologie et Parasitologie/Virologie
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PMID (identifiant de la référence Pubmed) : |
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(17375069) |
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| Titre : |
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Lentiviral vectors encoding HIV-1 polyepitopes induce broad CTL responses in vivo. |
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| Auteur(s) : |
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Maria Candela Iglesias1, Karine Mollier1, Anne-Sophie Beignon1, Philippe Souque1, Olivier Adotevi2, François Lemonnier2, Pierre Charneau1 |
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| Laboratoire : |
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| Résumé : |
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Lentiviral vectors have been tested as vaccination vectors in anti-tumoral and anti-viral models. They efficiently transduce dendritic cells and stimulate strong T-cell responses against the encoded antigen. However, their capacity to stimulate a cytotoxic T-lymphocyte (CTL) response against several antigens has not been evaluated. Broad anti-human immunodeficiency virus 1 (HIV-1) T-cell immune responses are important for the control of HIV replication. We evaluated the potential of polyepitope-encoding lentiviral vectors to induce broad anti-HIV CTL responses. We constructed two lentiviral vectors coding for an HLA-A2- or HLA-B7-restricted polyepitope and evaluated their immunogenicity by direct injection of vector particles in HLA-A2 or HLA-B7 transgenic mice. In vitro cytotoxicity assays showed that a single immunization induces a strong, diversified, and long-lasting CTL response in both mouse models. CTL responses were directed against all 13 epitopes in the HLA-A2 system and 8 out of 12 in the HLA-B7 system. A second immunization augmented the number of responding mice in the HLA-A2 system but not in the HLA-B7 system. HLA-B7-immunized mice mounted strong interferon-gamma (IFN-gamma)-secreting T-cell responses against a majority of the epitopes and lysed peptide-loaded target cells in vivo. CTL responses in HLA-B7 mice were only partially dependent on CD4 T-cell help. This work underlines the potential of lentiviral vectors as candidates for therapeutic vaccination against acquired immunodeficiency syndrome. |
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Langue du texte intégral : |
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Anglais |
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| Type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1038/sj.mt.6300135 |
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| Journal : |
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| Molecular Therapy (Mol Ther) |
| Publisher |
Nature Publishing Group: Open Access Hybrid Model Option B |
| ISSN |
1525-0016 (eISSN : 1525-0024) |
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| Audience : |
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internationale |
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| Date de publication : |
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06/2007 |
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Date de publication électronique : |
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20/03/2007 |
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| Volume : |
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15 |
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| Numéro : |
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6 |
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| Page, identifiant, ... : |
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1203-10 |
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