Polyelectrolyte capsules-containing HIV-1 p24 and poly I:C modulate dendritic cells to stimulate HIV-1-specific immune responses

W De Haes, S De Koker, C Pollard, D Atkinson, E Vlieghe, J Hoste, J Rejman, S De Smedt, J Grooten, G Vanham, E Van Gulck

    Research output: Contribution to journalA1: Web of Science-article

    Abstract

    Polyelectrolyte microcapsules (MCs) are potent protein delivery vehicles which can be tailored with ligands to stimulate maturation of dendritic cells (DCs). We investigated the immune stimulatory capacity of monocyte-derived DC (Mo-DC) loaded with these MCs, containing p24 antigen from human immunodeficiency virus type 1 (HIV-1) alone [p24-containing MC (MCp24)] or with the Toll-like receptor ligand 3 (TLR3) ligand poly I:C (MCp24pIC) as a maturation factor. MO-DC, loaded with MCp24pIC, upregulated CCR7, CD80, CD83, and CD86 and produced high amounts of interleukin-12 (IL-12) cytokine, to a similar extent as MCp24 in the presence of an optimized cytokine cocktail. MO-DC from HIV-infected patients under highly active antiretroviral therapy (HAART) exposed to MCp24 together with cytokine cocktail or to MCp24pIC expanded autologous p24-specific CD4(+) and CD8(+) T-cell responses as measured by interferon-gamma (IFN-gamma) and IL-2 cytokine production and secretion. In vivo relevance was shown by immunizing C57BL/6 mice with MCp24pIC, which induced both humoral and cellular p24-specific immune responses. Together these data provide a proof of principle that both antigen and DC maturation signal can be delivered as a complex with polyelectrolyte capsules to stimulate virus-specific T cells both in vitro and in vivo. Polyelectrolyte MCs could be useful for in vivo immunization in HIV-1 and other infections
    Original languageEnglish
    JournalMolecular Therapy
    Volume18
    Issue number7
    Pages (from-to)1408-1416
    Number of pages9
    ISSN1525-0016
    DOIs
    Publication statusPublished - 2010

    Keywords

    • B780-tropical-medicine
    • Viral diseases
    • HIV-1
    • AIDS
    • Monocytes
    • Dendritic cells
    • Capacity
    • Immune reconstitution
    • P24 antigen
    • Cytokine
    • CD4-positive-T-lymphocytes
    • CD8-positive-T-lymphocytes
    • In vivo
    • In vitro

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