Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Gene Ther. 2009 Jun;16(6):776-87. doi: 10.1038/gt.2009.31. Epub 2009 Apr 9.
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.
基因免疫策略主要集中在使用质粒 DNA 和基因枪。然而,仍需要进一步提高潜在 DNA 疫苗的效率、安全性和成本。通过基因枪传递的金颗粒涂层 DNA 格式昂贵、耗时且工艺复杂,并引起无菌安全问题。本研究旨在确定低压基因枪是否可以递送无载体的裸露 DNA 疫苗,而无需任何颗粒涂层,并产生与金颗粒涂层 DNA 疫苗相似的强烈抗原特异性免疫反应和有效的抗肿瘤作用。我们的结果表明,用无载体嵌合 CRT/E7 DNA 接种的小鼠导致 E7 特异性 CD8+ T 细胞前体数量显著增加,并显著提高了 E7 特异性抗体的滴度。此外,无载体裸露的 CRT/E7 DNA 疫苗对皮下表达 E7 的肿瘤和预先建立的表达 E7 的转移性肺肿瘤产生了强大的抗肿瘤作用。此外,与用金颗粒涂层 CRT/E7 DNA 疫苗接种的小鼠相比,用无载体裸露的 CRT/E7 DNA 疫苗接种的小鼠皮肤的烧灼感明显减少。我们得出结论,用低压基因枪递送的无载体裸露 CRT/E7 DNA 疫苗可产生类似的强大免疫反应和有效的抗肿瘤作用,副作用更少,比传统的金颗粒涂层 DNA 疫苗更方便。