Improving therapeutic HPV peptide-based vaccine potency by enhancing CD4+ T help and dendritic cell activation

Background: effective vaccination against human papillomavirus (hpv) represents an opportunity to control cervical cancer. peptide-based vaccines targeting hpv e6 and/or e7 antigens while safe,will most likely require additional strategies to enhance the vaccine potency. methods: we tested the hpv-16 e7 peptide-based vaccine in combination with a strategy to enhance cd4+ t help using a pan hla-dr epitope (padre) peptide and a strategy to enhance dendritic cell activation using the toll-like receptor 3 ligand,poly(i:c). results: we observed that mice vaccinated with e7 peptide-based vaccine in combination with padre peptide and poly(i:c) generated better e7-specific cd8+ t cell immune responses as well as significantly improved therapeutic anti-tumor effects against tc-1 tumors compared to e7 peptide-based vaccine with either padre peptide or poly(i:c) alone. furthermore,we found that intratumoral vaccination with the e7 peptide in conjunction with padre peptide and poly(i:c) generates a significantly higher frequency of e7-specific cd8 + t cells as well as better survival compared to subcutaneous vaccination with the same regimen in treated mice. conclusions: the combination of padre peptide and poly(i:c) with antigenic peptide is capable of generating potent antigen-specific cd8+ t cell immune responses and antitumor effects in vaccinated mice. our study has significant clinical implications for peptide-based vaccination. © 2010 wu et al; licensee biomed central ltd.