Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects

被引:11
|
作者
Chen, C-A [1 ]
Chang, M-C [2 ]
Sun, W-Z [2 ]
Chen, Y-L [1 ]
Chiang, Y-C [1 ]
Hsieh, C-Y [1 ]
Chen, S. M. [1 ]
Hsiao, P-N [2 ]
Cheng, W-F [1 ,3 ]
机构
[1] Natl Taiwan Univ, Dept Obstet & Gynecol, Coll Med, Taipei 10764, Taiwan
[2] Natl Taiwan Univ, Dept Anesthesiol, Coll Med, Taipei 10764, Taiwan
[3] Natl Taiwan Univ, Grad Inst Clin Med, Coll Med, Taipei 10764, Taiwan
关键词
noncarrier naked DNA vaccine; antigen; immunologic response; antitumor effect; TUMOR-SPECIFIC IMMUNITY; PLASMID DNA; GENE-GUN; CANCER-IMMUNOTHERAPY; PROTECTIVE IMMUNITY; FUSION PROTEIN; T-CELLS; IMMUNIZATION; VIRUS; ENHANCEMENT;
D O I
10.1038/gt.2009.31
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. Gene Therapy (2009) 16, 776-787; doi:10.1038/gt.2009.31; published online 9 April 2009
引用
收藏
页码:776 / 787
页数:12
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