The study of DNA vaccine potency against hamster oral papillomavirus-associated oral cancer

在之前的研究中，我们建立了一个高重复性的致癌模型，将DMBA应用与仓鼠舌粘膜的物理损伤相结合。利用该动物模型，我们通过分子克隆和病毒基因组测序证明了一种新型仓鼠口腔乳头瘤病毒（HOPV）的存在。在本研究中，我们使用HOPV仓鼠模型来测试单独接种Ll、L2、E6和E7基因或pDNA/普鲁兰复合物是否可以预防口腔癌的发展。并利用同一模型探讨了DNA疫苗的最适宜接种途径和多价DNA疫苗的抗肿瘤效果。因此，人们认识到，使用pDNA/普鲁兰复合物比裸pDNAs在预防口腔癌方面更有用。结果表明，抗肿瘤作用的大小依次为肌注bbb、口服bbb、粘膜注bbb、皮下注bbb。这些结果表明，肌肉注射DNA疫苗可能有助于hopv相关的癌症保护。利用电穿孔技术增强了DNA疫苗的抗癌作用。人们认识到电穿孔技术是将DNA疫苗插入组织细胞的一种非常有用的技术，因此在体内电穿孔是一种有效的DNA疫苗递送方法。本研究结果提示，多价DNA疫苗，尤其是Ll+L2多价DNA疫苗，具有增强抗癌作用的作用。总之，本研究表明，在仓鼠中，肌肉注射L1+L2多价DNA疫苗对hopv相关口腔癌的保护作用最高，这表明肌肉注射可能是DNA疫苗预防hopv相关癌症的最佳给药途径。很明显，体内电穿孔对于DNA疫苗的递送是有用的。

In a previous investigation, we developed a highly reproducible carcinogenesis model by combining DMBA application with physical wounding of the hamster lingual mucosa. Using this animal model, we demonstrated the presence of a novel hamster oral papillomavirus (HOPV) by the molecular cloning and sequencing of this viral genome. In this study, we used this HOPV hamster model to test whether vaccination with either the Ll, L2, E6 and E7 genes alone or pDNA/pullulan complex could prevent oral carcinoma development. And also we used the same model to investigate the most appropriate route for inoculation of DNA vaccine and antitumor efficacy of polyvalence DNA vaccines. As a result, it was recognized that using pDNA/pullulan complexes were more useful than the naked pDNAs for prevention of oral cancer. It was evident that the extent of antitumor efficacy was in the order intramuscular>oral intramucosal>subcutaneous administration. These results demonstrate that intramuscular administration of the DNA vaccine may be useful in HOPV-associated cancer protection. Using the electroporation, anti-cancer effects were enhanced in DNA vaccine. It was recognized the electroporation was very useful technique for the insert DNA vaccines to the cells of tissues, and it was therefore in vivo electroporation was a potent method for DNA vaccine delivery. From the result of this study, it was suggested that polyvalent DNA vaccines enhanced anti-cancer effects, in particular Ll+L2 polyvalent DNA vaccine. In conclusion, the present study has shown that in hamsters, the highest protection against HOPV-associated oral cancer development was produced by immunization with the L1+L2 polyvalent DNA vaccine by intramuscular administration, suggesting that intramuscular injection may be an optimal route of administration for DNA vaccine to prevent HOPV-associated cancer. And it became clear that it was useful to use in vivo electroporation for DNA vaccine delivery.