Abstract
The recent identification of tumor Ags as potential vaccines has prompted the search for efficient adjuvants and delivery systems, especially in the case of peptide-based vaccination protocols. Here, we investigated the adjuvant potential of the recombinant 40-kDa outer membrane protein of Klebsiella pneumoniae (P40) for specific CTL induction. We studied the CTL response induced in HLA-A*0201/K(b) transgenic mice immunized with peptides derived from two melanoma-associated differentiation Ags, the HLA-A*0201-restricted decapeptide Melan-A(26--35) substituted at position 2 and the K(b)-restricted tyrosinase-related protein 2(181--188) T cell epitope. We found that both peptides are able to generate a specific CTL response when mixed with the protein in the absence of conventional adjuvant. This CTL response is a function of the amount of P40 used for immunization. Moreover, the CTL response generated against the tyrosinase-related protein 2(181-188) peptide in presence of P40 is associated with tumor protection in two different experimental models and is independent of the presence of CD4(+) T lymphocytes. Thus, the recombinant bacterial protein P40 functions as a potent immunological adjuvant for specific CTL induction.
MeSH terms
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Adjuvants, Immunologic / administration & dosage*
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Adjuvants, Immunologic / chemical synthesis
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Animals
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Antigens, Neoplasm / administration & dosage
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Antigens, Neoplasm / immunology
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Bacterial Outer Membrane Proteins / administration & dosage
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Bacterial Outer Membrane Proteins / immunology*
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CD8-Positive T-Lymphocytes / immunology
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Cancer Vaccines / administration & dosage
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Cancer Vaccines / chemical synthesis*
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Cancer Vaccines / immunology
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Cytotoxicity, Immunologic / immunology*
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Drug Combinations
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Epitopes, T-Lymphocyte / immunology*
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Immunotherapy, Active / methods
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Injections, Subcutaneous
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Intramolecular Oxidoreductases / administration & dosage
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Intramolecular Oxidoreductases / immunology
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Klebsiella pneumoniae / immunology*
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Lymphocyte Depletion
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MART-1 Antigen
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Macromolecular Substances
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Melanoma, Experimental / immunology
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Melanoma, Experimental / pathology
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Melanoma, Experimental / prevention & control
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Transgenic
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Neoplasm Proteins / administration & dosage
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Neoplasm Proteins / immunology
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Neoplasm Transplantation
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Peptide Fragments / administration & dosage
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Peptide Fragments / chemical synthesis
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Peptide Fragments / immunology*
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T-Lymphocytes, Cytotoxic / immunology*
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Titrimetry
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Tumor Cells, Cultured / transplantation
Substances
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Adjuvants, Immunologic
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Antigens, Neoplasm
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Bacterial Outer Membrane Proteins
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Cancer Vaccines
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Drug Combinations
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Epitopes, T-Lymphocyte
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MART-1 Antigen
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Macromolecular Substances
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Mlana protein, mouse
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Neoplasm Proteins
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Peptide Fragments
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Intramolecular Oxidoreductases
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dopachrome isomerase