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 (20219934) |
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| titre : |
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Preclinical studies of a modified vaccinia virus Ankara-based HIV candidate vaccine: antigen presentation and antiviral effect. |
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| auteur(s) : |
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Samantha Brandler1, 2, Alice Lepelley1, Marion Desdouits3, Florence Guivel-Benhassine1, Pierre-Emmanuel Ceccaldi3, Yves Lévy2, 4, Olivier Schwartz1, 2, Arnaud Moris ( ) 1, 2 |
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| laboratoire : |
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| résumé : |
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Poxvirus-based human immunodeficiency virus (HIV) vaccine candidates are currently under evaluation in preclinical and clinical trials. Modified vaccinia virus Ankara (MVA) vectors have excellent safety and immunogenicity records, but their behavior in human cell cultures remains only partly characterized. We studied here various virological and immunological aspects of the interactions of MVA-HIV, a vaccine candidate developed by the French National Agency for AIDS Research (ANRS), with primary human cells. We report that MVA-HIV infects and drives Gag expression in primary macrophages, dendritic cells (DCs), and epithelial and muscle cells. MVA-HIV-infected DCs matured, efficiently presented Gag, Pol, and Nef antigens, and activated HIV-specific cytotoxic T lymphocytes (CTLs). As expected with this type of vector, infection was cytopathic and led to DC apoptosis. Coculture of MVA-HIV-infected epithelial cells or myotubes with DCs promoted efficient Gag antigen major histocompatibility complex class I (MHC-I) cross-presentation without inducing direct infection and death of DCs. Antigen-presenting cells (APCs) infected with MVA-HIV also activated HIV-specific CD4(+) T cells. Moreover, exposure of DCs to MVA-HIV or to MVA-HIV-infected myotubes induced type I interferon (IFN) production and inhibited subsequent HIV replication and transfer to lymphocytes. Altogether, these results show that MVA-HIV promotes efficient MHC-I and MHC-II presentation of HIV antigens by APCs without facilitating HIV replication. Deciphering the immune responses to MVA in culture experiments will help in the design of innovative vaccine strategies. |
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| domaine : |
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Sciences du Vivant/Microbiologie et Parasitologie
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1098-5514 |
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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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10.1128/JVI.02329-09 |
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| journal : |
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| Journal of Virology (J Virol) |
| Publisher |
American Society for Microbiology |
| ISSN |
0022-538X |
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| Audience : |
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internationale |
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| date de publication : |
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05/2010 |
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date de publication
électronique : |
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10/03/2010 |
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| volume : |
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84 |
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| numéro : |
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10 |
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| page, identifiant, ... : |
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5314-28 |
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| Descripteur(s) MeSH : |
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AIDS Vaccines – Animals – Antigen Presentation – CD4-Positive T-Lymphocytes – Cells – Cultured – Genetic Vectors – Humans – T-Lymphocytes – Cytotoxic – Vaccinia virus |
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