Serological response to an HPV16 E7 based therapeutic vaccine in women with high-grade cervical dysplasia

Gynecol Oncol. 2010 Feb;116(2):208-12. doi: 10.1016/j.ygyno.2009.05.044. Epub 2009 Jun 24.

Abstract

Purpose: Infection with oncogenic human papillomaviruses has been linked to the development of cervical neoplasia and cancer. The exclusive expression of E7, a viral oncogene, in infected cells makes this protein an ideal target for immunotherapy. We recently reported on the results of a trial in women with cervical carcinoma-in-situ using HspE7, a protein vaccine consisting of full length HPV16 E7 linked to a heat shock protein from M. bovis. The stimulating effects of HspE7 on specific cytotoxic T lymphocytes have been demonstrated in vitro and in (pre-)clinical trials. The induction of a B-cell response by HspE7 and its association with clinical outcome is unknown, and is the purpose of this study.

Experimental design: We measured the serum IgG levels against HPV16 E7 and HPV16 and -18 VLPs using a multiplexed Luminex based assay in 57 women with CIS who received the HspE7 vaccine.

Results: Vaccination with HspE7 results in a modest, yet maintained increase in HPV16 E7 specific IgG levels. While not significant, increased HPV16 E7 IgG levels appear to be correlated with a positive therapeutic effect. Women who were previously treated for recurrent disease (by LEEP) had significantly higher HPV16 E7 IgG levels compared with subjects without recurrent disease (p=0.01). In women with recurrent disease, higher IgG levels correlated with complete pathological response.

Conclusions: This study suggests that IgG levels could potentially be used as a marker for response to a therapeutic vaccine. Further translational investigations of the 'priming' of local immune responses using extirpative procedures should be explored.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Bacterial Proteins / immunology
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cervical Intraepithelial Neoplasia / immunology
  • Cervical Intraepithelial Neoplasia / therapy*
  • Cervical Intraepithelial Neoplasia / virology
  • Chaperonin 60 / immunology
  • Female
  • Human papillomavirus 16 / immunology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Mycobacterium bovis / immunology
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / pathology
  • Papillomavirus Vaccines / adverse effects
  • Papillomavirus Vaccines / immunology
  • Papillomavirus Vaccines / therapeutic use*
  • Uterine Cervical Dysplasia / immunology
  • Uterine Cervical Dysplasia / therapy*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / therapy*
  • Uterine Cervical Neoplasms / virology

Substances

  • Antibodies, Viral
  • Bacterial Proteins
  • Cancer Vaccines
  • Chaperonin 60
  • Immunoglobulin G
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • heat-shock protein 65, Mycobacterium
  • oncogene protein E7, Human papillomavirus type 16