Reversal of papilloma growth in rabbits therapeutically vaccinated against E6 with naked DNA and/or vesicular stomatitis virus vectors.
Persistent infection with high-risk human papillomaviruses (HPVs) is the greatest risk factor for the development of HPV-associated cancers. In this study rabbits bearing persistent and potentially malignant papillomas were used to test the efficacy of vaccination with a recombinant DNA and/or vesicular stomatitis virus (VSV) targeting the cottontail rabbit papillomavirus (CRPV) E6 protein. Immune responses were primed with either vector and boosted twice with the homologous or heterologous E6 vector. Over the course of 18 weeks, E6 vaccination reduced papilloma volumes to one third the volume in the controls, and the rabbits boosted with an heterologous vector tended to mount stronger responses. Small and medium-sized papillomas responded significantly but only slightly better than large papillomas. Finally the initial papilloma burden per rabbit, ranging from <100 mm(3) to >1000 mm(3), was not prognostic of antitumor efficacy. In summary both E6 vaccines elicited significant therapeutic immunity, and their sequential use tended to be advantageous.
Brandsma
Janet L
JL
Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. janet.brandsma@yale.edu
Shlyankevich
Mark
M
Su
Yuhua
Y
Zelterman
Daniel
D
Rose
John K
JK
Buonocore
Linda
L
D000818:Animals; D005260:Female; D005822:Genetic Vectors; D007117:Immunization, Secondary / Q000379:methods; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D010212:Papilloma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018116:Vesiculovirus / Q000235:genetics*
C469554:E6 protein, Cottontail rabbit papillomavirus; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA