Eradication of established HPV 16-expressing tumors by a single administration of a vaccine composed of a liposome-encapsulated CTL-T helper fusion peptide in a water-in-oil emulsion

Vaccine. 2006 Jun 12;24(24):5235-44. doi: 10.1016/j.vaccine.2006.03.079. Epub 2006 Apr 18.


Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide with half a million new cases per year. Despite the encouraging development of a preventive vaccine for HPV, a therapeutic vaccine for cervical cancer or pre-cancerous lesions remains a high priority. The preclinical study reported here used VacciMax((R)) (VM) to deliver a peptide-based vaccine composed of an HPV 16 E7-derived cytotoxic T lymphocyte (CTL) epitope fused to the T helper epitope PADRE (FP) and combined with CpG or lipopeptide adjuvant. In the study, C57BL/6 mice received 0.5million HPV 16-expressing C3 tumor cells. Mice were inoculated post-tumor challenge with a single s.c. injection of FP-CpG-VM on either day 4, 5, 6, 9, or 14. All mice that received the FP-CpG-VM vaccine were tumor-free to day 130 when the experiment was terminated. In contrast, only a minority of mice that received a control vaccine were tumor-free on day 60. Cytotoxicity assays, ELISPOT and intracellular staining for interferon (IFN)-gamma showed the immune response was specific for the selected CTL epitope. All mice that received the FP-CpG-VM vaccine remained tumor-free when re-challenged with 6million C3 cells. Cytotoxicity assays 4 months post-challenge showed that only splenocytes from mice inoculated with the FP-CpG-VM vaccine had high lysis activity. These results indicate that VacciMax((R)) causes a rapid, robust, durable and therapeutic CTL response to HPV 16 E7 protein expressing tumors.

MeSH terms

  • Animals
  • Emulsions
  • Epitopes, T-Lymphocyte*
  • Female
  • Human papillomavirus 16 / immunology*
  • Immunization
  • Liposomes
  • Malaria Vaccines / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Oligodeoxyribonucleotides / administration & dosage*
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Uterine Cervical Neoplasms / therapy*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*


  • CPG-oligonucleotide
  • Emulsions
  • Epitopes, T-Lymphocyte
  • Liposomes
  • Malaria Vaccines
  • Oligodeoxyribonucleotides
  • Oncogene Proteins, Viral
  • PADRE 45
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Vaccines, Synthetic
  • Viral Vaccines
  • oncogene protein E7, Human papillomavirus type 16