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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2004-07, Vol.53 (7), p.642-650
• Main Authors: HALLEZ, Sophie, SIMON, Philippe, HUBERT, Pascale, GERDAY, Colette, BURNY, Arsène, BONIVER, Jacques, FOIDART, Jean-Michel, DELVENNE, Philippe, JACOBS, Nathalie, MAUDOUX, Frédéric, DOYEN, Jean, NOËL, Jean-Christophe, BELIARD, Aude, CAPELLE, Xavier, BUXANT, Frédéric, FAYT, Isabelle, LAGROST, Anne-Cécile
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Viral - immunology; Antibody Formation; Antineoplastic agents; Bacterial Proteins - immunology; Biological and medical sciences; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Carrier Proteins - immunology; CD4; CD8; CD8-Positive T-Lymphocytes - immunology; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Human health sciences; human papillomavirus; Human papillomavirus 16; Humans; IFN-gamma; Immunoglobulin D - immunology; Immunologie & maladie infectieuse; Immunology & infectious disease; immunotherapy; Interferon-gamma - metabolism; Lipoproteins - immunology; Medical sciences; Oncogene Proteins, Viral - immunology; Oncologie; Oncology; Original; Papillomaviridae - immunology; Papillomavirus E7 Proteins; Papillomavirus Infections - immunology; Papillomavirus Infections - therapy; Papillomavirus Infections - virology; Papillomavirus Vaccines; Pharmacology. Drug treatments; Recombinant Fusion Proteins - immunology; Sciences de la santé humaine; T-Lymphocytes, Cytotoxic - immunology; Tumors; 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
• ISSN: 0340-7004; 1432-0851; 1432-0851
• DOI: 10.1007/s00262-004-0501-4

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). 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. 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. 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.