Genital infections with human papillomavirus (HPV) are increasingly re
cognized as a significant source of human disease; HPV is now implicat
ed in up to 90% of cervical carcinomas. Neutralizing antibodies agains
t papillomaviruses recognize conformational epitopes formed when viral
capsid proteins assemble into virions or virus-like particles. Immuni
zation with plasmid DNA encoding the major viral capsid protein L1 was
studied as a means of inducing neutralizing antibodies and protection
against virus challenge. In a cottontail rabbit papillomavirus (CRPV)
model, immunization with plasmid DNA encoding L1 elicited conformatio
nally specific neutralizing antibodies and provided immunity against p
apilloma formation upon challenge with CRPV. Immunization with DNA enc
oding the capsid protein may provide a means of protecting humans agai
nst HPV and would simplify the production of multivalent vaccines by c
ombining plasmids that encode the viral capsid proteins of different s
trains. This may be of importance given the multiplicity of HPV types
capable of causing disease.