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: Chao-Yi Wu, Archana Monie, Xiaowu Pang, Chien-Fu Hung, T-C Wu
• Journal: Journal of biomedical science (J Biomed Sci) Vol. 17 Pg. 88 (Nov 22 2010) ISSN: 1423-0127 [Electronic] England
• PMID: 21092195 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, immunology)
• Papillomavirus Vaccines (immunology)
• Peptides (genetics, immunology)
• Poly I-C (immunology)
• Uterine Cervical Neoplasms (immunology, prevention & control, virology)