Human papillomavirus vaccines.

Genital human papillomavirus (HPV) infections are the viral sexually transmitted diseases most frequently diagnosed that include anogenital condylomas and squamous intra-$bepithelial lesions, among which the precursors of invasive carcinomas of the uterine cervix. In animal PV models, vaccination against L1 and/or L2 viral capsid proteins provides an efficient protection against infection, involving virus type-specific neutralizing antibodies. Vaccination against non-structural E1, E2, E6 or E7 viral proteins does not prevent infection, unless administered altogether, but tends to stimulate regression, warranting the design of therapeutic vaccines. Prophylactic vaccines based on the use of virus-like particles (VLPs) obtained by auto-assembly of L1 or L1 and L2 proteins produced by recombinant DNA technology are under phase I/II clinical trials for HPV6/11 associated with condylomas and for HPV16, the most frequent oncogenic genotype. Second generation vaccines are chimeric proteins or VLPs incorporating one of the structural proteins (L1 or L2) fused to a non-structural protein (E6, E7 or E2), which should induce both humoral and cellular immunity. Vaccine valency (number of genotypes), route of administration (humoral versus local immunity), vaccinees (children, young adults, gender) and forms of vaccines (recombinant $LSalmonella typhimurium*I$L, edible plants expressing L1 and L2 proteins, DNA vaccines, synthetic antigenic peptides) are under study. End points to evaluate vaccine efficacy in phase III trials should include viral DNA detection and typing, and screening for low or high grade intraepithelial lesions. Therapeutic vaccines based on recombinant HPV E6 and/or E7 vaccinia virus, L2-E7 fusion proteins or E7 peptides corresponding to cytotoxic T cell epitopes are currently tested (phase I/II trials) in patients with cervical carcinomas of advanced clinical stages or high grade intraepithelial lesions. Animal studies, phase I/II clinical trials and implementation of the community support that HPV vaccines will constitute an efficient means to prevent carcinoma of the uterine cervix. Copyright 2000 Academic Press.