Effective induction of type 1 helper IgG2a and cytotoxic T-cell responses in mice following immunization with human papillomavirus type 16 E2 in MF59

Human papillomavirus (HPV) 16 E2-specific cell-mediated immunity to the early viral antigen E2 is associated with regression of natural infection in patients with cervical dysplasia. Vaccination strategies that activate this type of immune response may have application in the immunotherapeutic treatment of pre-existing HPV infections. The objective of this study was to test if cell-mediated immunity to E2 could be activated when delivered with the already licensed adjuvant MF59. We found that immunization of mice with E2 in MF59 stimulated T-cell responses when administered either intraperitoneally (IP) or subcutaneously (SC), and that the response was polarized to a Th-1 type IgG(2a) response in the IP immunized mice. The magnitude of the lymphoproliferative response was augmented by reducing the time interval between the primary and secondary immunizations from 12 to 4 wk. Stronger responses to the C-terminal third of E2 were detected, suggesting that one or more immunodominant epitopes were localized to this region. Significantly, immunization with E2 in MF59 IP was sufficient to stimulate an E2-specific cytotoxic T-cell response. This immunization regimen activates the components of a cell-mediated immunity that are predicted to be efficacious in clearance of pre-existing infection, and supports its testing in a papillomavirus challenge model, as the next step in the progression toward its development as an immunotherapeutic vaccine for use in humans.