Enhancement of DNA vaccine potency against hamster oral papillomavirus-associated oral cancer by electroporation in vivo

We previously developed a hamster oral papilloma virus (HOPV) tumor model. We also showed that immunization with a DNA vaccine consisting of naked plasmid DNA (pDNA) encoding the L1 region of the HOPV genome (pHOPV-L1) had a cancer suppressing effect in this model. Here, we investigated if the use of electroporation as a vaccine delivery system could enhance the effect of this vaccine. A pHOPV-L1 vaccine was generated and was inoculated (100 µg/animal) intramuscularly into hamsters (n=10 per group), who then underwent eight rounds of electroporation of 50, 100, or 200 V/cm (VE50, VE100, and VE200 group, respectively). Control groups (n=10 per group) were untreated (N), or were treated with electroporation alone (E50, E100, and E200 groups) or vaccination alone (V group). The animals then underwent carcinogenic treatment over the next 69 days, during which 9,10-dimethyl-1,2-benzanthracene (DMBA) was applied onto lingual mucosa and a lingual wound was created. Histopathological analysis of lingual tissue indicated that all of the animals in the N and E groups developed lingual carcinoma that was accompanied by koilocytosis in the squamous carcinoma lesions. In contrast, 4, 5, 7 and 9 animals in the V, VE50, VE100 and VE200 groups, respectively, showed no carcinoma lesions. All of the animals with carcinomas ultimately showed a decreasing trend in weight, as well as HOPV infection that was detected using real-time PCR analysis. On the other hand, all animals without carcinomas increased in weight over the entire course of the experiment and did not display HOPV infection. These data confirm that a vaccine consisting of naked pDNA from the L1 region of HOPV can suppress HOPV-associated cancer, and show that its cancer suppressing effects can be enhanced by low-voltage electroporation following inoculation. We conclude that low-voltage electroporation is a useful and safe delivery system for DNA vaccines and should be further exploited.