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.
Highlights
Cervical cancer is the 2nd leading cause of cancer deaths in women worldwide
We found that intratumoral vaccination with the E7 peptide-based vaccine in combination with Pan HLA-DR epitope (PADRE) peptide and poly(I:C) generates even higher frequency of E7-specific CD8+ T cells as well as better survival compared to subcutaneous vaccination in treated mice
Mice vaccinated with the E7 peptide in combination with PADRE peptide and poly(I:C) generate the highest frequency of E7-specific CD8+ T cells In order to determine the antigen-specific T cell immune responses in mice vaccinated with the combination of E7 peptide-based vaccine with PADRE peptide and poly(I:C), we performed intracellular cytokine staining followed by flow cytometry analyses
Summary
The primary etiological factor in the development of cervical cancer is infection by human papillomavirus (HPV) [1]. HPV infection is a necessary factor for the development and maintenance of cervical cancer and effective vaccination against HPV represents an opportunity to control cervical cancer Peptide-based vaccination has emerged as a potentially important strategy for the development of therapeutic HPV vaccination as they are considered to be safe, easy peptide-based vaccine potency that may potentially be suitable for clinical translation. 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
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