Development of an HPV vaccine for a broad spectrum of high-risk types

Abstract

Cervical cancer, the second most frequent gynecological malignancy in the world, is caused by infection with high-risk human papillomaviruses (HPV16, 18, and other 13 types). Vaccines protecting women from infection with high-risk HPVs can reduce prevalence of cervical cancer without costly screening for cervical precancerous lesions. Two vaccines containing HPV16 and 18 virus-like particles (VLPs), which were produced by self-assembly of the major capsid protein L1 of each HPV type, successfully induced type-specific neutralizing antibodies in the recipients of the large scale clinical trials and have been approved by several countries. Although HPV16 and HPV18 account for approximately 50% and 20% of cervical cancer, respectively, the remaining major issue to be addressed is how to prevent infection with other high-risk HPVs. Our and other studies have indicated that the HPV minor capsid protein L2 has several type-common neutralization epitopes and that immunization of animals with peptides having the L2-epitopes protects them against experimental challenge. Recently, we have shown that a type of chimeric VLP, HPV16 VLPs to which the type-common L2-epitope was added, induced in rabbits both the anti-HPV16 L1 neutralizing antibody at a high level and the anti-L2 cross-neutralizing antibody at lower but sufficient levels to be protective shown in the other animal experiments. Thus, this type of chimeric VLP seems likely to be one of the next-generation vaccine candidates for a broad spectrum of high-risk HPV types.