Developing an HPV vaccine to prevent cervical cancer and genital warts

The challenges of the journey from target identification through development of a prophylactic quadrivalent human papillomavirus (HPV) vaccine have been met in Gardasil®. Cervical cancer is the second leading cause of cancer-related death in women worldwide. Approximately 70% of cervical cancer is caused by infection with HPV types 16 and 18 and ∼90% of genital warts are caused by HPV types 6 and 11. The quadrivalent HPV vaccine was generated by expression of the major capsid protein (L1) of HPV types 16, 18, 6 and 11 in yeast. L1 proteins self assemble into pentamer structures and these pentamer structures come together to form virus-like particles (VLPs). The VLPs are antigenically indistinguishable from HPV virions. The VLPs contain no viral DNA and therefore the vaccine is non-infectious. Gardasil® is composed of VLPs of HPV types 16, 18, 6 and 11 conjugated to a proprietary amorphous aluminum hydroxyphosphate sulfate adjuvant. The results of a rigorous clinical program have demonstrated that the vaccine is safe and highly efficacious in preventing dysplasias, cervical intraepithelial neoplasias (CIN 1–3) the precursors of cervical cancer and external genital lesions caused by vaccine-HPV types. In conclusion, Gardasil® addresses a major medical need, that is, reduction of HPV-related disease including cervical cancer as a safe, immunogenic, and highly efficacious vaccine.