Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells.
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.
Schreibelt
Gerty
G
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Benitez-Ribas
Daniel
D
Schuurhuis
Danita
D
Lambeck
Annechien J A
AJ
van Hout-Kuijer
Maaike
M
Schaft
Niels
N
Punt
Cornelis J A
CJ
Figdor
Carl G
CG
Adema
Gosse J
GJ
de Vries
I Jolanda M
IJ
D001500:BCG Vaccine / Q000276:immunology / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000276:immunology / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000494:pharmacology; D011315:Preventive Medicine; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D014436:Typhoid-Paratyphoid Vaccines / Q000276:immunology / Q000494:pharmacology; D014612:Vaccines / Q000276:immunology / Q000494:pharmacology*; D014614:Vaccines, Synthetic / Q000378:metabolism / Q000494:pharmacology
D001500:BCG Vaccine; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D007252:Influenza Vaccines; D008024:Ligands; D011135:Polysaccharides, Bacterial; D051193:Toll-Like Receptors; D014436:Typhoid-Paratyphoid Vaccines; D014612:Vaccines; D014614:Vaccines, Synthetic; C057664:Vi polysaccharide vaccine, typhoid; D018664:Interleukin-12; D015232:Dinoprostone