Figure 2.

Therapeutic HPV DNA vaccination. Several methods of therapeutic vaccinations have been developed. Specifically, for HPV, therapeutic vaccines activate the adaptive immune system by targeting the E6 and/or E7 antigen(s). These methods include live vector–based (bacterial or viral vector) vaccines, peptide-/protein-based vaccines, cell-based (tumor cell or dendritic cell) vaccines, and nucleic acid–based (RNA or DNA) vaccines. While preventive vaccines elicit a humoral immune response through neutralizing antibodies, therapeutic vaccines utilize the cell-mediated immune system to control HPV infections. This schematic outlines therapeutic HPV DNA vaccination. DNA plasmids that encode for HPV antigens, such as early proteins 6 and 7 (E6, E7), are transfected into antigen presenting cells (APCs) such as dendritic cells (DCs). APCs are activated upon direct transfection of these HPV antigens or through indirect transfer of the antigens by way of cross-presentation. DCs home to draining lymph nodes where they can prime naïve T-cells upon presentation of antigenic peptides to T-cells via major histocompatibility complexes (MHCs) The interaction between the MHC molecules and the antigens (i.e., MHC:antigen [Ag] complex) with the T-cell receptor (TCR) is assisted by co-stimulatory compounds, namely B7 present on DCs and CD28 present on T-cells. MHC-I molecules present to CD8+ T-cells and MHC II molecules present to CD4+ T-cells to initiate a cell-mediated immune response. Activated CD8+ T-cells directly kill tumor cells by inducing apoptosis. This immune response is further supported by CD4+ T-cells, which assist in the killing of tumors.