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

Abstract

BackgroundEffective 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.MethodsWe 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).ResultsWe 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.ConclusionsThe 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.

Peptide-Conjugated PAMAM Dendrimer as a Universal DNA Vaccine Platform to Target Antigen-Presenting Cells

“…The universal peptide PADRE binds/activates cells bearing any of the 15 major forms of the HLA-DR and has been widely used as immune adjuvant (14,30,31). Its adjuvant (although modest) effect has been confirmed in this report (Fig.…”

Self-Adjuvanting Polymer–Peptide Conjugates As Therapeutic Vaccine Candidates against Cervical Cancer

“…(QAEPDRAHYNIVTFCCKCD; E7 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] ) which contains a CTL epitope (CD8 + cytotoxic T lymphocytes), and T-helper cell (CD4 + ) and B-cell epitopes ( Figure 1). 9 This combination makes 8Q an ideal candidate to stimulate long-term vaccine efficacy to kill cancer cells.…”

Prediction of Promiscuous Epitopes in the E6 Protein of Three High Risk Human Papilloma Viruses: A Computational Approach

“…Nevertheless, it is estimated that these two preventative vaccines will provide protection against cervical cancer caused by HPV 16 and 18 only (Govan, 2008). Also, administration of these vaccines in developing countries like India has proved severe side effects and even deaths in some cases which ultimately therapeutic vaccine on the other hand, which is considered to be safe, stable and easily producible (Wu et al, 2010) is the need of the hour as considerable population is already suffering from HPV infection worldwide. HPV E6 and E7 proteins though do not elicit strong immune response; transformation of HPV associated lesions (Ma et al, 2010) and form the ideal choice for the therapeutic vaccines.…”