CD34-derived dendritic cells transfected ex vivo with HIV-Gag mRNA induce polyfunctional T-cell responses in nonhuman primates

Authors

  • Gabrielle Romain,

    1. CEA, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies (iMETI), DSV, Fontenay-aux-Roses, France
    2. Université Paris-Sud, UMR E1, Orsay, France
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  • Ellen van Gulck,

    1. Virology Unit, Division of Microbiology, Department of Biomedical Sciences (HIV and Retrovirology Research Unit), Department of Microbiology, Institute of Tropical Medicine of Antwerp (ITMA), Antwerp, Belgium
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  • Olivier Epaulard,

    1. CEA, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies (iMETI), DSV, Fontenay-aux-Roses, France
    2. Université Paris-Sud, UMR E1, Orsay, France
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  • SangKon Oh,

    1. Baylor Institute for Immunology Research, Dallas, TX, USA
    2. INSERM U899, Paris, France
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  • Dapeng Li,

    1. Baylor Institute for Immunology Research, Dallas, TX, USA
    2. INSERM U899, Paris, France
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  • Gerard Zurawski,

    1. Baylor Institute for Immunology Research, Dallas, TX, USA
    2. INSERM U899, Paris, France
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  • Sandra Zurawski,

    1. Baylor Institute for Immunology Research, Dallas, TX, USA
    2. INSERM U899, Paris, France
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  • Antonio Cosma,

    1. CEA, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies (iMETI), DSV, Fontenay-aux-Roses, France
    2. Université Paris-Sud, UMR E1, Orsay, France
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  • Lucille Adam,

    1. CEA, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies (iMETI), DSV, Fontenay-aux-Roses, France
    2. Université Paris-Sud, UMR E1, Orsay, France
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  • Catherine Chapon,

    1. CEA, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies (iMETI), DSV, Fontenay-aux-Roses, France
    2. Université Paris-Sud, UMR E1, Orsay, France
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  • Biliana Todorova,

    1. CEA, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies (iMETI), DSV, Fontenay-aux-Roses, France
    2. Université Paris-Sud, UMR E1, Orsay, France
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  • Jacques Banchereau,

    1. Baylor Institute for Immunology Research, Dallas, TX, USA
    2. INSERM U899, Paris, France
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  • Nathalie Dereuddre-Bosquet,

    1. CEA, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies (iMETI), DSV, Fontenay-aux-Roses, France
    2. Université Paris-Sud, UMR E1, Orsay, France
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  • Guido Vanham,

    1. Virology Unit, Division of Microbiology, Department of Biomedical Sciences (HIV and Retrovirology Research Unit), Department of Microbiology, Institute of Tropical Medicine of Antwerp (ITMA), Antwerp, Belgium
    2. Faculty of Medicine and Pharmacy, Free University of Brussels (VUB), Brussels, Belgium
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  • Roger Le Grand,

    1. CEA, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies (iMETI), DSV, Fontenay-aux-Roses, France
    2. Université Paris-Sud, UMR E1, Orsay, France
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  • Frédéric Martinon

    Corresponding author
    1. Université Paris-Sud, UMR E1, Orsay, France
    2. INSERM U899, Paris, France
    • CEA, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies (iMETI), DSV, Fontenay-aux-Roses, France
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Full Correspondence: Dr. Frédéric Martinon, Service d'Immuno-Virologie, iMETI, CEA, 18 route du Panorama, 92265 Fontenay-aux-Roses, France

Fax: +33-1-4654-7726

e-mail: frederic.martinon@cea.fr

Abstract

The pivotal role of DCs in initiating immune responses led to their use as vaccine vectors. However, the relationship between DC subsets involved in antigen presentation and the type of elicited immune responses underlined the need for the characterization of the DCs generated in vitro. The phenotypes of tissue-derived APCs from a cynomolgus macaque model for human vaccine development were compared with ex vivo-derived DCs. Monocyte/macrophages predominated in bone marrow (BM) and blood. Myeloid DCs (mDCs) were present in all tested tissues and were more highly represented than plasmacytoid DCs (pDCs). As in human skin, Langerhans cells (LCs) resided exclusively in the macaque epidermis, expressing CD11c, high levels of CD1a and langerin (CD207). Most DC subsets were endowed with tissue-specific combinations of PRRs. DCs generated from CD34+ BM cells (CD34-DCs) were heterogeneous in phenotype. CD34-DCs shared properties (differentiation and PRR) of dermal and epidermal DCs. After injection into macaques, CD34-DCs expressing HIV-Gag induced Gag-specific CD4+ and CD8+ T cells producing IFN-γ, TNF-α, MIP-1β, or IL-2. In high responding animals, the numbers of polyfunctional CD8+ T cells increased with the number of booster injections. This DC-based vaccine strategy elicited immune responses relevant to the DC subsets generated in vitro.

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