Increased Immunity to Cottontail Rabbit Papillomavirus Infection in EIII/JC Inbred Rabbits after Vaccination with a Mutant E6 That Correlates with Spontaneous Regression

Our previous studies showed that a progressive cottontail rabbit papillomavirus (CRPV) strain containing a single amino acid change in E6 (E6G252E) induced papilloma regression in EIII/JC inbred rabbits. This finding implied that the point mutation might cause an increase in the antigenicity of the mutant versus the wild-type E6. To test this hypothesis, groups of four EIII/JC inbred rabbits were immunized with wild-type CRPVE6, CRPVE6G252E, CRPV E5, or with vector alone. A gene gun delivery system was used to deliver the DNA vaccines. Two of four rabbits from both E6G252E- and wild-type E6-vaccinated groups were free of papillomas at week 12 after viral challenge. Significantly smaller papillomas were found on E6G252E-vaccinated rabbits than on E6-, E5-, and control vector-vaccinated rabbits (p = 0.01, unpaired Student t test) and these small papillomas regressed at week 20 after viral challenge. E5 vaccination failed to provide protection against viral challenge, and the mean papilloma size was also comparable to that of the control vector-vaccinated rabbits (p > 0.05, unpaired Student t test). We conclude that a single amino acid change in the CRPV E6 protein (G252E) increased protection against wild-type infectious CRPV.