Document Detail


Polyelectrolyte capsules-containing HIV-1 p24 and poly I:C modulate dendritic cells to stimulate HIV-1-specific immune responses.
MedLine Citation:
PMID:  20461059     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Winni De Haes; Stefaan De Koker; Charlotte Pollard; Derek Atkinson; Erika Vlieghe; Jessy Hoste; Joanna Rejman; Stefaan De Smedt; Johan Grooten; Guido Vanham; Ellen Van Gulck
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-11
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  18     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-02     Completed Date:  2010-09-30     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1408-16     Citation Subset:  IM    
Affiliation:
Institute of Tropical Medicine of Antwerp, Department of Microbiology, Unit Virology, Antwerp, Belgium. wdehaes@itg.be
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MeSH Terms
Descriptor/Qualifier:
Animals
Dendritic Cells / immunology*
Drug Carriers / chemistry*
Female
HIV Core Protein p24 / chemistry,  immunology*
HIV-1 / immunology
Humans
Immunity, Cellular / immunology
Immunity, Humoral / immunology
Interferon-gamma / metabolism
Interleukin-12 / metabolism
Interleukin-2 / metabolism
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence
Poly I-C / chemistry,  immunology*
Polymers / chemistry*
Chemical
Reg. No./Substance:
0/Drug Carriers; 0/HIV Core Protein p24; 0/Interleukin-2; 0/Polymers; 187348-17-0/Interleukin-12; 24939-03-5/Poly I-C; 82115-62-6/Interferon-gamma
Comments/Corrections

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