A DNA vaccine encoding the major capsid protein L1 of cottontail rabbit papillomavirus (CRPV) was constructed and administered intracutaneously (i.c.) to rabbits as supercoiled plasmids bound to gold beads using a specialized delivery device ("gene gun"). L1 DNA-vaccinated rabbits developed cellular proliferative responses to CRPV virus-like particles and developed high titered antibodies with neutralizing activity to CRPV. Following experimental challenge with CRPV, all of the L1 DNA-vaccinated rabbits, vs none of the controls, were protected from papilloma formation. These results demonstrate that i.c. vaccination of rabbits with the L1 papillomavirus capsid gene can induce antibodies that protect against subsequent papillomavirus infection.