Development of an L2-based HPV vaccine to generate broad immunity

DESCRIPTION (provided by applicant): Cervical cancer accounts for nearly 10% of all cancers in women and is the second leading cause of death from cancer in women worldwide. More than 470,000 cases are diagnosed every year and 250,000 deaths are related solely to cervical cancer. Human papillomavirus (HPV) is broadly accepted to play a causative role in the development of cervical cancer and also other anogenital and head and neck cancers, as well as skin cancer. Therefore, the prevention of HPV infection generates an effective preventive procedure in the struggle against various types of cancer. Seventy percent of cervical cancer is caused by infection with HPV types 16 and 18, with the remaining 30% caused by 15 other identified oncogenic HPV types. The current approved vaccines, based on L1 virus-like particles, provide protection against HPV 16 and 18 and the cutaneous types HPV 6 and 11. Neither broad protection against all known types that are related to cervical cancer nor protection against the skin-cancer-causing virus types is covered by these vaccines. Generating this protection is the goal of the described work to develop a novel vaccine based on an L2 approach that provides broad immunity to prevent HPV-associated infection and diseases. This L2 peptide approach is supported by significant research that describes the ability of L2 epitopes to induce neutralizing antibodies. Different strategies have been employed to present L2 epitope sequences capable of generating neutralizing antibodies, including fusion proteins of similar or divergent HPV types, larger or smaller sections of the L2 protein, and incorporation of an adjuvant. A successful L2-based vaccine could be developed if it neutralizes a significantly greater number of strains than the L1 vaccines. Combined with an appropriate adjuvant, based on Dynavax adjuvant technologies, the development of a broadly immunogenic L2-based HPV vaccine has a strong probability of success. The overall goal for this project is to demonstrate an L2 fusion protein vaccine ready for testing in non-human primates. By characterizing the immunogenicity of the L2 epitope fusion constructs, we expect to define a lead candidate antigen for application in later stages. PUBLIC HEALTH RELEVANCE: Human papillomavirus (HPV) plays a causative role in the development of cervical cancer in women, with more than 470,000 cases diagnosed every year and 250,000 deaths related solely to cervical cancer. The current approved vaccines only provide protection against virus types that cause 70% of cervical cancer. The goal of the described work is to develop a novel vaccine that provides broader immunity for prevention of HPV-associated infection to protect against all currently known oncogenic and the most important cutaneous HPV types.