Intranasal vaccination with a recombinant vesicular stomatitis virus expressing cottontail rabbit papillomavirus L1 protein provides complete protection against papillomavirus-induced disease.

Immunizations with live recombinant vesicular stomatitis viruses (rVSV) expressing foreign viral proteins have successfully protected animals from challenges with several heterologous viruses. We developed an rVSV expressing the major capsid protein (L1) of cottontail rabbit papillomavirus (CRPV) and tested the efficacy of protection following CRPV challenge. An rVSV expressing L1 of CRPV (VSV-L1) was characterized for the protective ability afforded by intranasal, intradermal, or intramuscular vaccination in rabbits subsequently challenged with CRPV. Protein expression of L1 in VSV-L1 was confirmed by radioimmunoprecipitation assays. Nuclear localization of L1 was demonstrated by indirect immunofluorescence assays. Immunized rabbits elicited significant VSV neutralization and VLP-L1 enzyme-linked immunosorbent assay titers. VSV-L1 vaccination was not associated with weight loss or any other adverse clinical signs in the rabbit model. VSV shedding in nasal secretions occurred in some rabbits, peaking at 4 to 6 days after intranasal vaccination, with no further shedding after day 6. Specific humoral immunity to the L1 protein was consistently seen after a single VSV-L1 vaccination when administered through an intradermal or intramuscular route or after a boost via the intranasal route. Rabbits were completely protected from CRPV-induced papillomas after VSV-L1 vaccination and boost given intranasally or intramuscularly. Vaccination with VSV-L1 is a novel approach to prevent papillomavirus-induced disease and demonstrates a potential strategy for developing a human papillomavirus vaccine that can be given without injection.