| Autor: |
Lasarte, J. J., Casares, N., Gorraiz, M., Herváas-Stubbs, S., Arribillaga, L., Mansilla, C., Durantez, M., Llopiz, D., Sarobe, P., Borrás-Cuesta, F., Jesús Prieto, Leclerc, C. |
| Jazyk: |
angličtina |
| Rok vydání: |
2007 |
| Předmět: |
|
| Zdroj: |
Scopus-Elsevier |
| Popis: |
Vaccination strategies based on the in vivo targeting of Ags to dendritic cells (DCs) are needed to improve the induction of specific T cell immunity against tumors and infectious agents. In this study, we have used a recombinant protein encompassing the extra domain A from fibronectin (EDA), an endogenous ligand for TLR4, to deliver Ags to TLR4-expressing DC. The purified EDA protein was shown to bind to TLR4-expressing HEK293 cells and to activate the TLR4 signaling pathway. EDA also stimulated the production by DC of proinflammatory cytokines such as IL-12 or TNF-alpha and induced their maturation in vitro and in vivo. A fusion protein between EDA and a cytotoxic T cell epitope from OVA efficiently presented this epitope to specific T cells and induced the in vivo activation of a strong and specific CTL response. Moreover, a fusion protein containing EDA and the full OVA also improved OVA presentation by DC and induced CTL responses in vivo. These EDA recombinant proteins protected mice from a challenge with tumor cells expressing OVA. These results strongly suggest that the fibronectin extra domain A may serve as a suitable Ag carrier for the development of antiviral or antitumoral vaccines. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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