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

(2010) MOLECULAR THERAPY. 18(7). p.1408-1416
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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.
Keywords
COATED PLGA MICROPARTICLES, IN-VITRO, CD8(+) T-CELLS, CROSS-PRESENTATION, AUTOLOGOUS HIV-1, ANTIGEN DELIVERY, INFECTION, NANOPARTICLES, MICROCAPSULES, THERAPY

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Citation

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Chicago
De Haes, Winni, Stefaan De Koker, Charlotte Pollard, Derek Atkinson, Erika Vlieghe, Jessy Hoste, Joanna Rejman, et al. 2010. “Polyelectrolyte Capsules-containing HIV-1 P24 and Poly I:C Modulate Dendritic Cells to Stimulate HIV-1-specific Immune Responses.” Molecular Therapy 18 (7): 1408–1416.
APA
De Haes, Winni, De Koker, S., Pollard, C., Atkinson, D., Vlieghe, E., Hoste, J., Rejman, J., et al. (2010). Polyelectrolyte capsules-containing HIV-1 p24 and poly I:C modulate dendritic cells to stimulate HIV-1-specific immune responses. MOLECULAR THERAPY, 18(7), 1408–1416.
Vancouver
1.
De Haes W, De Koker S, Pollard C, Atkinson D, Vlieghe E, Hoste J, et al. Polyelectrolyte capsules-containing HIV-1 p24 and poly I:C modulate dendritic cells to stimulate HIV-1-specific immune responses. MOLECULAR THERAPY. 2010;18(7):1408–16.
MLA
De Haes, Winni, Stefaan De Koker, Charlotte Pollard, et al. “Polyelectrolyte Capsules-containing HIV-1 P24 and Poly I:C Modulate Dendritic Cells to Stimulate HIV-1-specific Immune Responses.” MOLECULAR THERAPY 18.7 (2010): 1408–1416. Print.
@article{1017037,
  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.},
  author       = {De Haes, Winni and De Koker, Stefaan and Pollard, Charlotte and Atkinson, Derek and Vlieghe, Erika and Hoste, Jessy and Rejman, Joanna and De Smedt, Stefaan and Grooten, Johan and Vanham, Guido and Van Gulck, Ellen},
  issn         = {1525-0016},
  journal      = {MOLECULAR THERAPY},
  keyword      = {COATED PLGA MICROPARTICLES,IN-VITRO,CD8(+) T-CELLS,CROSS-PRESENTATION,AUTOLOGOUS HIV-1,ANTIGEN DELIVERY,INFECTION,NANOPARTICLES,MICROCAPSULES,THERAPY},
  language     = {eng},
  number       = {7},
  pages        = {1408--1416},
  title        = {Polyelectrolyte capsules-containing HIV-1 p24 and poly I:C modulate dendritic cells to stimulate HIV-1-specific immune responses},
  url          = {http://dx.doi.org/10.1038/mt.2010.82},
  volume       = {18},
  year         = {2010},
}

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