Evaluation of an E6 and E7 multiepitope fused or not to ubiquitin against HPV16 derived cervical cancer

Abstract

Responsible for the deaths of 230 thousand women each year, the cervical cancer is the second most common cancer among women worldwide. Only in Brazil more than 18,000 new cases of this disease it is estimated in 2010 and HPV infection is a major risk factor for its etiopathogenesis. The HPV16 and HPV18 are the types most commonly identified in cervical cancer and therefore the focus of many studies at treatment of this pathology. The discovery of the involvement of cellular immunity in response to infection has allowed the study of various immunotherapeutic strategies against the HPV and cervical cancer. Two prophylactic vaccines against HPV16 and HPV18 were licensed, however, due to the high cost of the vaccine, a large proportion of the population of developing countries has no access to this vaccination, thus making it difficult to reduce the high incidence of cervical cancer. Furthermore, these vaccines do not benefit women already infected with the virus and cervical cancer. For these reasons the Butantan Institute is developing a vaccine against established HPV infection that could be accessible to the majority of the population. The E7 and E6 oncoproteins of HPV are involved in uncontrolled proliferation and cellular transformation and for this reason, E6 and E7 have been of particular interest for the development of therapeutic vaccines. Our laboratory is developing a vaccine compound of epitopes of these two oncoproteins and to enhance a cytotoxic cellular immune response against the tumor, these epitopes was conjugated with Ubiquitin. Thus, this project will involve the expression and purification of chimeric protein containing E6E7 with and without Ubiquitin. Tests will be carried out to check the prophylactic and therapeutic potential of this new vaccine against induced tumor in mice and to assess the immunogenic response of these vaccines. (AU)