Protection against Papillomavirus with a Polynucleotide Vaccine

Genital infectionswith human papillomavirus(HPV) are increasingly recognized as a significant source of human disease; HPV is now implicated in up to 90% of cervicalcarcinomas.Neutralizing antibodies against papillomaviruses recognize conformational epitopes formed when viral capsid proteins assemble into virions or virus-like particles. Immunization 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, immuniza­ tion with plasmid DNA encoding L1 elicitedconformationally specific neutralizing antibodies and provided immunity against papilloma formation upon challenge with CRPV. Immunization with DNA encoding the capsid protein may provide a means of protecting humans against HPV and would simplifythe production of multivalent vaccines by combining plasmids that encode the viral capsid proteins of different strains. This may be of importance given the multiplicity of HPV types capable of causing disease. Genital infection with human papillomavirus (HPV) is in­ creasingly recognized as a source of sexually transmitted dis­ ease in the United States [1], Infection with HPV may cause genital condylomas and cervical neoplasia and may be associ­ ated with as many as 90% of cervical carcinomas [2]. There are at least 76 types of HPV, and -40 infect the human repro­ ductive tract [3]. Types 16, 18, 31, 33, 35, 45, and 56 are commonly found in premalignant dysplasias and cervical carci­ nomas and are thought to be etiologic agents for cancer, whereas types 6, 11, 42, 43, and 44 are the most common causes of genital condylomas [3]. Both the carcinoma- and condyloma-associated types may be found in cervical intraepi­ thelial neoplasia [3].