|
Title
|
|
|
|
Polyelectrolyte capsules-containing HIV-1 p24 and poly I:C modulate dendritic cells to stimulate HIV-1-specific immune responses
| |
|
Author
|
|
|
|
| |
|
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-γ (IFN-γ) 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. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Molecular therapy. - New York
| |
|
Publication
|
|
|
|
New York
:
2010
| |
|
ISSN
|
|
|
|
1525-0016
| |
|
DOI
|
|
|
|
10.1038/MT.2010.82
| |
|
Volume/pages
|
|
|
|
18
:7
(2010)
, p. 1408-1416
| |
|
ISI
|
|
|
|
000279398900020
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|