Figure 5.

Schematic model depicting the mechanism of action of therapeutic vaccine. The mechanism for anti-HPV activity constitutes through its targeting of E6 and E7 oncoproteins upon APCs for activation of CD8+ and CD4+ cells in the TME. Administration of varying therapeutic HPV vaccine types results in the delivery of different forms of antigen into the body. DNA plasmids encoding HPV oncoproteins E6 and E7 can be transfected into dendritic cells through DNA vaccines or infection of transformed live vector-based vaccines. These antigens are then transcribed into RNA; however, RNA can also be introduced into the cell through RNA vaccines. Transcribed RNA is further translated into antigen proteins or long peptides. Antigen proteins or long peptides can also be taken up by the dendritic cell through phagocytosis after administration of a protein-based or peptide-based vaccine. These proteins or peptides are processed into short peptides by proteasomes and loaded onto an MHC class I molecule in the endoplasmic reticulum (ER) to be presented to T-cell receptors on CD8+ T cells. In addition, dendritic cells or tumor cells can be prepared ex vivo to express target antigens on MHC class I molecules with necessary co-stimulatory molecules and be administered back into the body as whole cell-based vaccines through adoptive transfer to prime T cells. On the other hand, the protein or peptide antigens taken up by the dendritic cell can be degraded into smaller fragments by proteases in the endosome. The endosome containing the small antigenic peptides is then fused with the exosome containing the MHC class II molecule, during which the antigenic peptide is loaded onto the MHC class II molecule. The MHC class II–antigenic peptide complex is then transported to the cell surface to be presented to T-cell receptors on CD4+ T cells. Adapted and modified with open access permission from (80).