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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología experimental > DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista >

Combination of a TLR4 ligand and anaphylatoxin C5a for the induction of antigen-specific cytotoxic T cell responses
Autor(es) : Rudilla, F. (Francesc)
Fayolle, C. (Catherine)
Casares, N. (Noelia)
Durantez, M. (Maika)
Arribillaga, L. (Laura)
Lozano, T. (Teresa)
Villanueva, L. (Lorea)
Pio, R. (Rubén)
Sarobe, P. (Pablo)
Leclerc, C. (Claude)
Prieto, J. (Jesús)
Lasarte, J.J. (Juan José)
Palabras clave : EDA
C5a
Dendritic cell
Adjuvant
Vaccine
Fusion protein
Fecha incorporación: 2012
Editorial : Elsevier
Versión del editor: http://www.sciencedirect.com/science/article/pii/S0264410X12002460
ISSN: 1873-2518
Cita: Rudilla F, Fayolle C, Casares N, Durantez M, Arribillaga L, Lozano T, et al. Combination of a TLR4 ligand and anaphylatoxin C5a for the induction of antigen-specific cytotoxic T cell responses. Vaccine 2012 Apr 16;30(18):2848-2858.
Resumen
The complement system and Toll-like receptors (TLR) are key innate defense systems which might interact synergistically on dendritic cells (DC) to reinforce adaptive immunity. In a previous work, we found that the extra domain A from fibronectin EDA (an endogenous ligand for TLR4) can favour antigen delivery to DC and induce their maturation. Given the potential of anaphylatoxins to cause inflammation and activation of myeloid cells, we hypothesized that a fusion protein between EDA, and anaphylatoxins C3a, C4a or C5a together with an antigen might improve the immunogenicity of the antigen. Naked DNA immunization with a construct expressing the fusion protein between C5a, EDA and the cytotoxic T cell epitope SIINFEKL from ovalbumin, induced strong antigen specific T cell responses. The purified recombinant fusion protein EDA-SIINFEKL-C5a induced activation of dendritic cells, the production of proinflammatory cytokines/chemokines and stimulated antigen presenting cell migration and NK cell activation. As compared to EDA-SIINFEKL, the fusion protein EDA-SIINFEKL-C5a did not induce the production of the immunosuppressive molecules IL-10, CCL17, CCL1, CXCL12 or XCL1 by DC. Moreover, EDA-SIINFEKL-C5a induced strong specific T cell responses in vivo and protected mice against E.G7-OVA tumor growth more efficiently than EDA-SIINFEKL or SIINFEKL-C5a recombinant proteins. Our results suggest that fusion proteins containing EDA, the anaphylatoxin C5a and the antigen may serve as a suitable strategy for the development of anti-tumor or anti-viral vaccines.
Enlace permanente: http://hdl.handle.net/10171/21671
Aparece en las colecciones: DA - CIMA - Oncología - Biomarcadores - Artículos de Revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista

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