Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects.
Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8+ T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
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CA
Chen
M-C
MC
Chang
W-Z
WZ
Sun
Y-L
YL
Chen
Y-C
YC
Chiang
C-Y
CY
Hsieh
S M
SM
Chen
P-N
PN
Hsiao
W-F
WF
Cheng
D000818:Animals; D019470:Biolistics / Q000379:methods; D002021:Buffers; D002057:Burns, Chemical / Q000209:etiology; D039521:CD11c Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured / Q000276:immunology; D003713:Dendritic Cells / Q000378:metabolism; D020405:Dermis / Q000187:drug effects / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004337:Drug Carriers / Q000494:pharmacology / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte; D005260:Female; D005434:Flow Cytometry; D006046:Gold / Q000009:adverse effects; D007167:Immunotherapy / Q000379:methods*; D007271:Injections, Intradermal; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D011312:Pressure; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*
D002021:Buffers; D039521:CD11c Antigen; D019496:Cancer Vaccines; D004337:Drug Carriers; D018984:Epitopes, T-Lymphocyte; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; D006046:Gold; D008156:Luciferases