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

J Biomed Sci. 2010 Nov 22;17(1):88. doi: 10.1186/1423-0127-17-88.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Inbred C57BL
  • Papillomaviridae / immunology
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / immunology*
  • Papillomavirus Vaccines / immunology*
  • Peptides / genetics
  • Peptides / immunology*
  • Poly I-C / immunology
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / prevention & control
  • Uterine Cervical Neoplasms / virology


  • Antiviral Agents
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Peptides
  • oncogene protein E7, Human papillomavirus type 16
  • Poly I-C