Chimeric virus-like particles of the human papillomavirus type 16 (HPV 16) as a prophylactic and therapeutic vaccine

Abstract

Infection by certain human papillomaviruses (HPV), most notably HPV types 16 and 18, is the major risk factor for cervical cancer. Worldwide, this disease represents the second most frequent malignant tumor in women; thus, there is urgent need for efficient therapy and prevention. The natural history of cervical cancer and its precursors (cervical intraepithelial neoplasias), as well as animal experiments, strongly suggest that the immune system controls both the primary infection (by neutralizing antibodies directed against the major structural protein L1) and the progression of the disease (via cytotoxic T cells specific for the viral oncoproteins expressed in transformed cells, e.g., E7). By the expression of an HPV 16 L1E7 fusion protein, we have generated chimeric virus-like particles (CVLP). Immunization of mice with CVLPs induces neutralizing antibodies directed against L1 virus-like particles (devoid of the E7 portion) and E7-specific T cells as measured in vitro. Vaccinated animals are protected against tumor growth following inoculation of syngeneic HPV 16-transformed cells. In addition, we observed a therapeutic effect of vaccination on pre-existing tumors. This data allowed us to conclude that CVLPs are suitable for prevention and therapy of HPV infection. A vaccine based on HPV 16 L1E7 CVLPs is currently under development.