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Induction of specific immune responses by polycation-based vaccines.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2002 Nov 01; Vol. 169 (9), pp. 5217-26. - Publication Year :
- 2002
-
Abstract
- The s.c injection of tumor Ag-derived, MHC class I-binding peptides together with cationic poly-amino acids (e.g., poly-L-arginine; pR) has been shown to protect animals against a challenge with tumor cells expressing the respective peptide(s). Given our only restricted knowledge about immunogenic tumor-associated peptides, we sought to determine whether this pR-based vaccination protocol would also induce protective cancer immunity if large proteins were used instead of peptide epitopes. We found that the intracutaneous administration of the model Ag beta-galactosidase (beta-gal) together with pR (referred to as pR-based protein vaccine; pR-PV) was significantly more potent in protecting mice against the growth of beta-gal-expressing RENCA cells than the protein alone. Coadministration of pR enhanced both the beta-gal-induced specific humoral and CD8 response. The protective effect required CD8(+), but neither CD4(+) T lymphocytes nor beta-gal-specific Abs. beta-Gal priming of protective CD8(+) T lymphocytes was found to be CD4(+) T cell-independent, to take place within the draining lymph nodes, and to be accomplished by day 5 after vaccination. Ablation of the injection sites as early as 1.5 h after pR-PV administration still led to protection in a large proportion of the animals, indicating that certain protein Ags administered intradermally in the context of polycations are quickly transported to the draining nodes, where they induce molecular and cellular events resulting in the helper-independent priming and expansion of Tc1 cells. However, optimal protection required the prolonged presence of the injection site, suggesting that pR-PV injection facilitates the formation of a cutaneous depot of Ag-charged cells capable of migration and T cell activation.
- Subjects :
- Adjuvants, Immunologic administration & dosage
Animals
Antigen-Presenting Cells immunology
Antigen-Presenting Cells metabolism
Antineoplastic Agents administration & dosage
Antineoplastic Agents immunology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Cations administration & dosage
Clone Cells
Cytotoxicity, Immunologic
Epitopes, T-Lymphocyte immunology
Growth Inhibitors administration & dosage
Growth Inhibitors immunology
Histocompatibility Antigens Class I immunology
Injections, Intradermal
Injections, Subcutaneous
Kidney Neoplasms immunology
Kidney Neoplasms prevention & control
Kidney Neoplasms therapy
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
Peptides administration & dosage
Polyamines administration & dosage
Polyelectrolytes
Tumor Cells, Cultured
Vaccines administration & dosage
beta-Galactosidase administration & dosage
Cations immunology
Peptides immunology
Polyamines immunology
Vaccines immunology
beta-Galactosidase immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 169
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 12391240
- Full Text :
- https://doi.org/10.4049/jimmunol.169.9.5217