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

Abstract Licensed human papillomavirus (HPV) vaccines do not target cutaneous genus beta (ß)HPV types implicated in skin cancer development in immunosuppressed individuals. The conserved N-terminus of minor capsid protein offers the opportunity to develop broad-spectrum vaccine candidates. We employed a sequential immunization strategy using N-terminal L2 fragments of five ßHPVs that induced a broad humoral immunity against different ßHPV types. Four monoclonal antibodies (mAb) were generated that cross-neutralized multiple ßHPV types and conferred in vivo protection against potentially oncogenic HPV5/24/38. MAb epitopes were identified and inserted 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 HPV5/38/76 infection. Chimeric VLPs displaying βHPV L2 cross-neutralizing epitopes represent promising broad-spectrum vaccine candidates against βHPV infection and the associated risk of keratinocytic skin cancerogenesis in immunosuppressed patients.