Synergy effects of Polyinosinic-polycytidylic acid, CpG oligodeoxynucleotide, and cationic peptides to adjuvant HPV E7 epitope vaccine through preventive and therapeutic immunization in a TC-1 grafted mouse model.

Cross-talk by pattern recognition receptors may facilitate the maturation of dendritic cells and fine tune the immune response. Thus, the inclusion of ligands agonistic to multiple receptors in a vaccine formula may be an effective strategy to elicit robust antitumor cellular immunity. We tested the adjuvant effects and possible synergy of CpG (CpG oligodeoxynucleotide), Poly I:C (polyinosinic-polycytidylic acid) and the cationic peptide Cramp (cathelicidin-related antimicrobial peptide) formulated in a DOTAP (1,2-dioleoyl-3-trimethylammonium-propane) liposomal HPV E7 epitope vaccine on a TC-1 grafted mouse model. The vaccine formulations were administered both preventively and therapeutically. Based on our results, both CpG and Poly I:C-adjuvanted vaccines abolished tumor development in a preventive trial and significantly suppressed tumor growth in a therapeutic trial. Increased interferon (IFN)-γ expression and potent memory T cells in splenocytes as well as elevated CD8+IFN-γ+ cells in both spleen and tumor tissue indicated an elevated E7-specific cellular immune response. Although synergistic effects were detected between CpG and Poly I:C, their adjuvant effects were not enhanced further when combined with Cramp. Because the enhancement of tumor antigen-specific cellular immune responses is vital for the clearance of infected and cancerous cells, our results contribute a potential adjuvant combination for cancer vaccines.