L2 epitope presenting virus-like particles as broad-spectrum vaccine candidates targeting genus beta human papillomaviruses.

Licensed human papillomavirus (HPV) vaccines do not target cutaneous ßHPV types implicated in skin cancer development in immunosuppressed individuals. The conserved N-terminus of minor capsid protein L2 contains cross-neutralization epitopes, offering the opportunity to develop broad-spectrum vaccine candidates. A sequential immunization strategy using N-terminal L2 fragments of five ßHPVs induced type-common humoral immunity. Four monoclonal antibodies (mAb) were generated that cross-neutralized multiple ßHPV types and conferred in vivo protection against potentially oncogenic HPV5/38/24. MAb epitopes were inserted individually into the DE-surface loop of HPV16 L1 virus-like particles (VLP). Immunizations with chimeric VLPs induced cross-neutralizing antibodies against multiple ßHPV types and conferred in vivo protection against HPV5 infection. Chimeric VLPs displaying ßHPV-L2 cross-neutralizing epitopes are promising broad-spectrum vaccine candidates against the plethora of ßHPVs. Immunization of patients prior to immunosuppression may reduce the burden of ßHPV infection and thus lower their highly increased risk to develop keratinocytic skin cancer.