Gene gun-mediated intracutaneous vaccination with papillomavirus E7 gene delays cancer development of papillomavirus-induced skin papillomas on rabbits

Abstract

High-risk human papillomavirus (HPV) E6 and E7 viral oncogenes are expressed in HPV-associated cancers, and thus represent tumor-specific antigens. We used the cottontail rabbit papillomavirus (CRPV) rabbit model to test whether vaccination with either the E6 or E7 genes alone could prevent or delay carcinoma development. CRPV-induced papillomas on 24 rabbits were allowed to grow for 3 months without any treatment intervention. An immunization protocol using gene gun-mediated intracutaneous administration of DNA plasmids encoding the E6 or the E7 gene or vector only, respectively was initiated at this time point. Carcinoma development was followed up to 24 months after virus infection. Within this period, five rabbits died due to other causes but without carcinoma; one from the vector control group, and two each from the E6- and E7-vaccinated groups. The remaining seven rabbits from the vector control group developed carcinoma within 7–17 months. The remaining six E6-vaccinated rabbits developed cancer within 8–15 months. There was no delay in cancer development for the E6-vaccinated rabbits compared to the vector-injected rabbits. Some delay in cancer development in the remaining E7-vaccinated rabbits was observed; one developed cancer at month 23 and a second was without cancer at month 24. In addition, some E7-vaccinated rabbits with primary skin carcinomas had fewer lung metastases (<2) compared to vector-vaccinated controls (20+). These results suggested that gene gun-mediated intracutaneous immunization with papillomavirus early gene E7 but not E6 delayed carcinoma development of papillomavirus-induced lesions.