Single-Dose Therapeutic Vaccination of Mice with Vesicular Stomatitis Virus Expressing Human Papillomavirus Type 16 E7 Protein

Department of Obstetrics, Gynecology, and Reproductive Sciences; Investigative Medicine Program; Microbiology Graduate Program; Department of Pathology; Departments of Genetics, Molecular Biophysics and Biochemistry, and Therapeutic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510

^* To whom correspondence should be addressed. Email: daniel.dimaio{at}yale.edu.

	Abstract

We are developing recombinant attenuated vesicular stomatitis virus (VSV) as a vaccine vector to generate humoral- and cell-mediated immune responses. Here, we explore the use of VSV vaccines for cancer immunotherapy. Immunotherapy targeting high-risk human papillomavirus (HPV) lesions has the potential to benefit HPV-infected individuals and cervical cancer patients by generating cytotoxic T cells that kill tumor cells that express viral antigens. A single dose of VSV expressing the HPV16 E7 oncogene was used for therapeutic vaccination of mice bearing TC-1 syngeneic tumors which express HPV16 E7. HPV16 E7-specific T-cells were generated and displayed cytotoxic activity against the tumor cells. By 14 days post-vaccination, average tumor volumes were 10-fold less in the vaccinated group compared to mice that received the empty vector VSV, and regression of pre-existing tumors occurred in some cases. This anti-tumor effect was CD8 T-cell dependent. Our results demonstrate anti-tumor responses to HPV16 E7 and suggest that recombinant VSV-based vaccination should be explored as a therapeutic strategy for cervical carcinoma and other HPV-associated cancers.