Therapeutic HPV DNA vaccines

Abstract

Human papillomavirus (HPV) has been associated with several human cancers, including cervical cancer, vulvar cancer, vaginal and anal cancer, and a subset of head and neck cancers. The identification of HPV as an etiological factor for HPV-associated malignancies creates the opportunity for the control of these cancers through vaccination. Currently, the preventive HPV vaccine using HPV virus-like particles has been proven to be safe and highly effective. However, this preventive vaccine does not have therapeutic effects, and a significant number of people have established HPV infection and HPV-associated lesions. Therefore, it is necessary to develop therapeutic HPV vaccines to facilitate the control of HPV-associated malignancies and their precursor lesions. Among the various forms of therapeutic HPV vaccines, DNA vaccines have emerged as a potentially promising approach for vaccine development due to their safety profile, ease of preparation and stability. However, since DNA does not have the intrinsic ability to amplify or spread in transfected cells like viral vectors, DNA vaccines can have limited immunogenicity. Therefore, it is important to develop innovative strategies to improve DNA vaccine potency. Since dendritic cells (DCs) are key players in the generation of antigen-specific immune responses, it is important to develop innovative strategies to modify the properties of the DNA-transfected DCs. These strategies include increasing the number of antigen-expressing/antigen-loaded DCs, improving antigen processing and presentation in DCs, and enhancing the interaction between DCs and T cells. Many of the studies on DNA vaccines have been performed on preclinical models. Encouraging results from impressive preclinical studies have led to several clinical trials.