DNA-based immunization by in vivo transfection of dendritic cells.
Delivery of antigen in a manner that induces effective, antigen-specific immunity is a critical challenge in vaccine design. Optimal antigen presentation is mediated by professional antigen-presenting cells (APCs) capable of taking up, processing and presenting antigen to T cells in the context of costimulatory signals required for T-cell activation. Developing immunization strategies to optimize antigen presentation by dendritic cells, the most potent APCs, is a rational approach to vaccine design. Here we show that cutaneous genetic immunization with naked DNA results in potent, antigen-specific, cytotoxic T lymphocyte-mediated protective tumor immunity. This method of immunization results in the transfection of skin-derived dendritic cells, which localize in the draining lymph nodes. These observations provide a basis for further development of DNA-based vaccines and demonstrate the feasibility of genetically engineering dendritic cells in vivo.
Condon
C
C
Department of Dermatology, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
Watkins
S C
SC
Celluzzi
C M
CM
Thompson
K
K
Falo
L D
LD
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D019470:Biolistics; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005240:Feasibility Studies; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D007114:Immunization / Q000379:methods*; D008198:Lymph Nodes / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000473:pathology; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D019444:Vaccines, DNA; D010047:Ovalbumin