title: Improving therapeutic HPV peptide-based vaccine potency by enhancing CD4+ T help and dendritic cell activation.
abstract: 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.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Chao-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Archana
authors.initials: A
authors.lastname: Monie
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Pang
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008810:Mice, Inbred C57BL; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011070:Poly I-C / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000821:virology
chemical_list: D000998:Antiviral Agents; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D010455:Peptides; C059731:oncogene protein E7, Human papillomavirus type 16; D011070:Poly I-C