Abstract
Currently dendritic cell (DC)-based vaccines are explored in clinical trials, predominantly in cancer patients. Murine studies showed that only maturation with Toll-like receptor (TLR) ligands generates mature DCs that produce interleukin-12 and promote optimal T-cell help. Unfortunately, the limited availability of clinical-grade TLR ligands significantly hampers the translation of these findings into DC-based vaccines. Therefore, we explored 15 commonly used preventive vaccines as a possible source of TLR ligands. We have identified a cocktail of the vaccines BCG-SSI, Influvac, and Typhim that contains TLR ligands and is capable of optimally maturing DCs. These DCs (vaccine DCs) showed high expression of CD80, CD86, and CD83 and secreted interleukin-12. Although vaccine DCs exhibited an impaired migratory capacity, this could be restored by addition of prostaglandin E(2) (PGE(2); vaccine PGE(2) DCs). Vaccine PGE(2) DCs are potent inducers of T-cell proliferation and induce Th1 polarization. In addition, vaccine PGE(2) DCs are potent inducers of tumor antigen-specific CD8(+) effector T cells. Finally, vaccine PGE(2)-induced DC maturation is compatible with different antigen-loading strategies, including RNA electroporation. These data thus identify a new clinical application for a mixture of commonly used preventive vaccines in the generation of Th1-inducing clinical-grade mature DCs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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BCG Vaccine / immunology
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BCG Vaccine / pharmacology
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Cell Differentiation / drug effects*
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Cell Differentiation / immunology
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Cell Movement / drug effects
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Cells, Cultured
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Dendritic Cells / drug effects*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dendritic Cells / physiology
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Dinoprostone / pharmacology
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Diphtheria-Tetanus-acellular Pertussis Vaccines / immunology
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Diphtheria-Tetanus-acellular Pertussis Vaccines / pharmacology
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Drug Evaluation, Preclinical
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Humans
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Influenza Vaccines / immunology
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Influenza Vaccines / pharmacology
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Interleukin-12 / metabolism
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Ligands
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Monocytes / drug effects*
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Monocytes / immunology
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Monocytes / metabolism
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Monocytes / physiology
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Polysaccharides, Bacterial / immunology
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Polysaccharides, Bacterial / pharmacology
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Preventive Medicine
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Toll-Like Receptors* / immunology
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Toll-Like Receptors* / metabolism
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Typhoid-Paratyphoid Vaccines / immunology
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Typhoid-Paratyphoid Vaccines / pharmacology
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Vaccines / immunology
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Vaccines / pharmacology*
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Vaccines, Synthetic / metabolism
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Vaccines, Synthetic / pharmacology
Substances
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BCG Vaccine
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Diphtheria-Tetanus-acellular Pertussis Vaccines
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Influenza Vaccines
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Ligands
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Polysaccharides, Bacterial
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Toll-Like Receptors
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Typhoid-Paratyphoid Vaccines
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Vaccines
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Vaccines, Synthetic
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Vi polysaccharide vaccine, typhoid
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Interleukin-12
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Dinoprostone