title: Polyelectrolyte capsules-containing HIV-1 p24 and poly I:C modulate dendritic cells to stimulate HIV-1-specific immune responses.
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.
authors.affiliation: Institute of Tropical Medicine of Antwerp, Department of Microbiology, Unit Virology, Antwerp, Belgium. wdehaes@itg.be
authors.forename: Winni
authors.initials: W
authors.lastname: De Haes
authors.forename: Stefaan
authors.initials: S
authors.lastname: De Koker
authors.forename: Charlotte
authors.initials: C
authors.lastname: Pollard
authors.forename: Derek
authors.initials: D
authors.lastname: Atkinson
authors.forename: Erika
authors.initials: E
authors.lastname: Vlieghe
authors.forename: Jessy
authors.initials: J
authors.lastname: Hoste
authors.forename: Joanna
authors.initials: J
authors.lastname: Rejman
authors.forename: Stefaan
authors.initials: S
authors.lastname: De Smedt
authors.forename: Johan
authors.initials: J
authors.lastname: Grooten
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.forename: Ellen
authors.initials: E
authors.lastname: Van Gulck
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D016655:HIV Core Protein p24 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D011070:Poly I-C / Q000737:chemistry / Q000276:immunology*; D011108:Polymers / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D016655:HIV Core Protein p24; D007376:Interleukin-2; D011108:Polymers; D018664:Interleukin-12; D007371:Interferon-gamma; D011070:Poly I-C
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