title: Therapeutic efficacy of vesicular stomatitis virus-based E6 vaccination in rabbits.
abstract: Millions of people worldwide are currently infected with human papillomaviruses (HPVs). A therapeutic HPV vaccine would have widespread applicability because HPV-associated lesions are difficult to treat and may progress to carcinoma. We developed three attenuated VSV recombinants expressing the cottontail rabbit papillomavirus (CRPV) early protein E6 for use as vaccines. In cultured cells, two vectors expressed different levels of the E6 protein, and one expressed a ubiquitin-E6 fusion protein. All three were tested for therapeutic efficacy in the cottontail rabbit papillomavirus (CRPV)-rabbit model. Mock vaccination had no effect on papilloma growth. In contrast, inoculation with any of the VSV-E6 vaccines reduced the rate of papilloma growth to as little as 24% the rate in the controls. In five experiments, these effects were achieved after a single immunization. Furthermore, complete papilloma regression occurred in some rabbits observed for 4 months. A VSV-based papillomavirus E6 vaccine could have significant advantages over other therapeutic HPV vaccine candidates described to date.
authors.affiliation: Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520-8016, USA. janet.brandsma@yale.edu
authors.forename: Janet L
authors.initials: JL
authors.lastname: Brandsma
authors.forename: Mark
authors.initials: M
authors.lastname: Shlyankevich
authors.forename: Linda
authors.initials: L
authors.lastname: Buonocore
authors.forename: Anjeanette
authors.initials: A
authors.lastname: Roberts
authors.forename: Steven M
authors.initials: SM
authors.lastname: Becker
authors.forename: John K
authors.initials: JK
authors.lastname: Rose
mesh_terms: D000818:Animals; D005260:Female; D007117:Immunization, Secondary; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000628:therapy*; D011817:Rabbits; D014611:Vaccination; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*
chemical_list: C469554:E6 protein, Cottontail rabbit papillomavirus; D009856:Oncogene Proteins, Viral; D014765:Viral Vaccines