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

Abstract

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.

Cathelicidins Modulate TLR-Activation and Inflammation

“…In addition, intranasal vaccination of mice using a nanoparticle-based vaccine for an H1N1-ovalbumin influenza virus, also benefits from IDR peptides as adjuvant, which together with c-di-AMP, induced a strong humoral and cellular immune response (174). Furthermore, subcutaneous vaccination of mice with the HPV E7 epitope of human papillomavirus (HPV) using CRAMP as adjuvant, reduced HPV-induced tumor growth (175). Finally, besides their effect on anti-viral vaccinations, IDR peptides were also shown to improve vaccination efficiency against other types of pathogens.…”

“…In gastric or colon tumors, where the expression of LL-37 is reduced (185), treatment with LL-37 activates caspaseindependent apoptosis and reduces tumor progression (186). Additionally, the application of CRAMP as adjuvant for HPV vaccination reduces tumor growth, albeit no direct anti-tumor effects of CRAMP were observed when used to treat HPVinduced tumors (175).…”

Immunogenicity of Varicella-Zoster Virus Glycoprotein E Formulated with Lipid Nanoparticles and Nucleic Immunostimulators in Mice

“…In our previous reports, we proved that encapsulation of economical nucleic acid immunostimulators including polyinosinic-polycytidylic acid (Poly I:C) and the natural phosphodiester CpG oligodeoxynucleotide (CpG ODN) into poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles showed excellent efficacy in therapeutic TC-1-grafted tumor models, in which CMI responses play decisive roles [ 23 , 24 ]. Although this economical adjuvant system also showed potential roles in VZV-gE CMI responses, the application of PLGA carriers is approved by the FDA for only chemical medicines, not vaccines.…”

Polysaccharide-based nanomedicines for cancer immunotherapy: A review

“…The former is usually found in bacteria and the latter is a synthetic analogue of double-stranded RNAs from viral-infected mammalian cells [ [251] , [252] , [253] , [254] ]. The combination of these two substances was reported to demonstrate synergistic effects to stimulate T cell responses and thus were explored as promising immune adjuvants for immunotherapeutic vaccines [ 255 , 256 ]. Despite their effectiveness, this combination would result in severe side effects.…”