Phase I/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein-based vaccine in women with oncogenic HPV-positive cervical intraepithelial neoplasia

Cancer Immunol Immunother. 2004 Jul;53(7):642-50. doi: 10.1007/s00262-004-0501-4. Epub 2004 Feb 17.


Purpose: Infection with oncogenic human papillomavirus (HPV) and HPV-16 in particular is a leading cause of anogenital neoplasia. High-grade intraepithelial lesions require treatment because of their potential to progress to invasive cancer. Numerous preclinical studies have demonstrated the therapeutic potential of E7-directed vaccination strategies in mice tumour models. In the present study, we tested the immunogenicity of a fusion protein (PD-E7) comprising a mutated HPV-16 E7 linked to the first 108 amino acids of Haemophilus influenzae protein D, formulated in the GlaxoSmithKline Biologicals adjuvant AS02B, in patients bearing oncogenic HPV-positive cervical intraepithelial neoplasia (CIN).

Methods: Seven patients, five with a CIN3 and two with a CIN1, received three intramuscular injections of adjuvanted PD-E7 at 2-week intervals. Three additional CIN1 patients received a placebo. CIN3 patients underwent conization 8 weeks postvaccination. Cytokine flow cytometry and ELISA were used to monitor antigen-specific cellular and antibody responses from blood taken before and after vaccine or placebo injection.

Results: Some patients had preexisting systemic IFN-gamma CD4+ (1/10) and CD8+ (5/10) responses to PD-E7. Vaccination, not placebo injection, elicited systemic specific immune responses in the majority of the patients. Five vaccinated patients (71%) showed significantly increased IFN-gamma CD8+ cell responses upon PD-E7 stimulation. Two responding patients generated long-term T-cell immunity toward the vaccine antigen and E7 as well as a weak H. influenzae protein D (PD)-directed CD4+ response. All the vaccinated patients, but not the placebo, made significant E7- and PD-specific IgG.

Conclusions: The encouraging results obtained from this study performed on a limited number of subjects justify further analysis of the efficacy of the PD-E7/AS02B vaccine in CIN patients.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / immunology
  • Antibody Formation
  • Bacterial Proteins / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Carrier Proteins / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin D / immunology
  • Interferon-gamma / metabolism
  • Lipoproteins / immunology
  • Oncogene Proteins, Viral / immunology*
  • Papillomaviridae / immunology*
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / therapy*
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines*
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Uterine Cervical Dysplasia / immunology
  • Uterine Cervical Dysplasia / therapy*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / therapy*
  • Uterine Cervical Neoplasms / virology
  • Vaccination


  • Antibodies, Viral
  • Bacterial Proteins
  • Cancer Vaccines
  • Carrier Proteins
  • Immunoglobulin D
  • Lipoproteins
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Recombinant Fusion Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • Interferon-gamma
  • glpQ protein, Haemophilus influenzae