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Lentiviral vectors encoding HIV-1 polyepitopes induce broad CTL responses in vivo.
Iglesias M. C., Mollier K., Beignon A.-S., Souque P., Adotevi O., Lemonnier F., Charneau P.
Molecular Therapy 15, 6 (2007) 1203-10 - http://hal.archives-ouvertes.fr/hal-00167663
Sciences du Vivant/Microbiologie et Parasitologie/Virologie
(17375069)
Lentiviral vectors encoding HIV-1 polyepitopes induce broad CTL responses in vivo.
Maria Candela Iglesias1, Karine Mollier1, Anne-Sophie Beignon1, Philippe Souque1, Olivier Adotevi2, François Lemonnier2, Pierre Charneau1
1 :  Virologie moléculaire et Vectorologie
Institut Pasteur de Paris – CNRS : URA3015
25-28 rue du Docteur Roux 75724 Paris Cedex 15
France
2 :  Immunité Cellulaire Antivirale
Institut Pasteur de Paris
25-28 rue du Docteur Roux, F-75724 Paris Cedex 15
France
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.
Anglais

Articles dans des revues avec comité de lecture
10.1038/sj.mt.6300135
Molecular Therapy (Mol Ther)
Publisher Nature Publishing Group: Open Access Hybrid Model Option B
ISSN 1525-0016 (eISSN : 1525-0024)
internationale
06/2007
20/03/2007
15
6
1203-10