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

Winni De Haes, Stefaan De Koker UGent, Charlotte Pollard UGent, Derek Atkinson, Erika Vlieghe, Jessy Hoste, Joanna Rejman UGent, Stefaan De Smedt UGent, Johan Grooten UGent and Guido Vanham, et al. (2010) MOLECULAR THERAPY. 18(7). p.1408-1416
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
COATED PLGA MICROPARTICLES, IN-VITRO, CD8(+) T-CELLS, CROSS-PRESENTATION, AUTOLOGOUS HIV-1, ANTIGEN DELIVERY, INFECTION, NANOPARTICLES, MICROCAPSULES, THERAPY
journal title
MOLECULAR THERAPY
Mol. Ther.
volume
18
issue
7
pages
1408 - 1416
Web of Science type
Article
Web of Science id
000279398900020
JCR category
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
JCR impact factor
7.149 (2010)
JCR rank
10/158 (2010)
JCR quartile
1 (2010)
ISSN
1525-0016
DOI
10.1038/mt.2010.82
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1017037
handle
http://hdl.handle.net/1854/LU-1017037
date created
2010-08-03 11:09:45
date last changed
2010-08-19 15:18:44
@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},
}

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, W., 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.