TY - JOUR
T1 - Enhancement of DNA vaccine potency against hamster oral papillomavirus-associated oral cancer by electroporation in vivo
AU - Jinno, Masato
AU - Isomura, Madoka
AU - Sato, Nobuaki
AU - Torii, Yasuyoshi
AU - Yoshida, Waka
AU - Sugita, Yoshihiko
AU - Kubo, Katsutoshi
AU - Maeda, Hatsuhiko
N1 - Funding Information:
This research was supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, under a Grant-in-Aid for Scientific Research C (Grant No. 15K11031).
Publisher Copyright:
© 2017 The Hard Tissue Biology Network Association Printed in Japan, All rights reserved.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
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U2 - 10.2485/jhtb.26.127
DO - 10.2485/jhtb.26.127
M3 - Article
AN - SCOPUS:85017347665
VL - 26
SP - 127
EP - 134
JO - Journal of Hard Tissue Biology
JF - Journal of Hard Tissue Biology
SN - 1341-7649
IS - 2
ER -