Fowlpox virus recombinants expressing HPV-16 E6 and E7 oncogenes for the therapy of cervical carcinoma elicit humoral and cell-mediated responses in rabbits

J Transl Med. 2010 Apr 21:8:40. doi: 10.1186/1479-5876-8-40.

Abstract

Background: Around half million new cases of cervical cancer arise each year, making the development of an effective therapeutic vaccine against HPV a high priority. As the E6 and E7 oncoproteins are expressed in all HPV-16 tumour cells, vaccines expressing these proteins might clear an already established tumour and support the treatment of HPV-related precancerous lesions.

Methods: Three different immunisation regimens were tested in a pre-clinical trial in rabbits to evaluate the humoral and cell-mediated responses of a putative HPV-16 vaccine. Fowlpoxvirus (FP) recombinants separately expressing the HPV-16 E6 (FPE6) and E7 (FPE7) transgenes were used for priming, followed by E7 protein boosting.

Results: All of the protocols were effective in eliciting a high antibody response. This was also confirmed by interleukin-4 production, which increased after simultaneous priming with both FPE6 and FPE7 and after E7 protein boost. A cell-mediated immune response was also detected in most of the animals.

Conclusion: These results establish a preliminary profile for the therapy with the combined use of avipox recombinants, which may represent safer immunogens than vaccinia-based vectors in immuno-compromised individuals, as they express the transgenes in most mammalian cells in the absence of a productive replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Antibody Specificity / immunology
  • Cell Extracts
  • Cell Line, Tumor
  • Chickens
  • Female
  • Fowlpox virus / genetics*
  • Humans
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / immunology*
  • Mice
  • Oncogene Proteins, Viral / genetics*
  • Papillomavirus E7 Proteins / genetics*
  • Rabbits
  • Recombination, Genetic
  • Repressor Proteins / genetics*
  • T-Lymphocytes, Cytotoxic / immunology
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / therapy*
  • Uterine Cervical Neoplasms / virology

Substances

  • Cell Extracts
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • oncogene protein E7, Human papillomavirus type 16