Enhanced CTL response by controlled intracellular trafficking of antigen in dendritic cells following DNA vaccination
| Autor: | Yoshinobu Takakura, Mitsuhiro Matono, Xin Guan, Atsushi Kawase, Makiya Nishikawa, Keiko Isaji |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Ovalbumin
Antigen presentation Freund's Adjuvant Genetic Vectors Pharmaceutical Science Biology Major histocompatibility complex Epitope DNA vaccination Cell Line Interferon-gamma Mice Antigen MHC class I Vaccines DNA Cytotoxic T cell Animals Antigens Antigen Presentation Dendritic Cells Molecular biology Mice Inbred C57BL CTL Protein Transport Electroporation biology.protein Female Plasmids T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 135(3) |
| ISSN: | 1873-4995 |
| Popis: | To elicit a cytotoxic T lymphocytes (CTL) response efficiently after DNA vaccination, we constructed several plasmid DNA (pDNA) vectors encoding the major histocompatibility complex (MHC) class I-restricted epitope peptide (SIINFEKL) of ovalbumin (OVA) or OVA protein with modified intracellular trafficking. An in vitro antigen presentation assay was carried out using DC2.4 cells, a dendritic cell line, to examine the potentials of the constructs following direct transfection. Among the vectors, pPep-ER, pDNA encoding antigen peptide combined with an endoplasmic reticulum (ER)-retention signal, exhibited a significant ability of antigen presentation compared with the counterpart without the signal. Based on the in vitro results, we carried out in vivo immunization experiments using pPep-ER via the intradermal or intramuscular route in combination with electroporation in mice. pPep-ER showed an efficient antigen-specific CTL induction and the effect was superior to that exhibited by the positive control, OVA in complete Freund's adjuvant (CFA). The levels of interferon gamma (IFN-gamma) released from spleen cells were significantly increased by pPep-ER compared with pPep-free. Immunization with pPep-ER also exhibited a high inhibitory effect on the growth of E.G7 tumor. These results indicate that DNA vaccination with the pDNA vector expressing a MHC class I epitope peptide with controlled intracellular trafficking is a promising method of inducing an antigen-specific CTL response via direct presentation. |
| Databáze: | OpenAIRE |
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