+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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 Immunology, ImmunoTherapy 53(7): 642-650



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 012410217

Download citation: RISBibTeXText

PMID: 14985860

DOI: 10.1007/s00262-004-0501-4


Related references

Use of cytokine flow cytometry to monitor cellular immune response to a human papillomavirus type 16 E7-derived vaccine Phase I/II trial in women with HPV16 positive grade 3 cervical intraepithelial neoplasia. Journal of Human Virology 4(3): 154, May-June, 2001

A phase I trial of a human papillomavirus (HPV) peptide vaccine for women with high-grade cervical and vulvar intraepithelial neoplasia who are HPV 16 positive. Clinical Cancer Research 6(9): 3406-3416, 2000

Safety and Immunogenicity of a Human Papillomavirus Peptide Vaccine (CIGB-228) in Women with High-Grade Cervical Intraepithelial Neoplasia: First-in-Human, Proof-of-Concept Trial. Isrn Obstetrics and Gynecology 2011: 292951, 2011

A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3. Oncoimmunology 4(10): E1031439, 2015

Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet 386(10008): 2078-2088, 2016

Analysis of E6 variants of human papillomavirus type 33, 52 and 58 in Japanese women with cervical intraepithelial neoplasia/cervical cancer in relation to their oncogenic potential. Cancer Letters 170(1): 19-24, September 10, 2001

A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clinical Cancer Research 15(1): 361-367, 2009

Socioeconomic status and the risk of cervical intraepithelial neoplasia grade 3 among oncogenic human papillomavirus DNA-positive women with equivocal or mildly abnormal cytology. Cancer 104(1): 61-70, 2005

Smoking is a risk factor for cervical intraepithelial neoplasia grade 3 among oncogenic human papillomavirus DNA-positive women with equivocal or mildly abnormal cytology. Cancer Epidemiology, Biomarkers and Prevention 14(5): 1165-1170, 2005

Detection of E5 protein in human papillomavirus type 16 positive cervical intraepithelial neoplasia exfoliated cells. Journal of Cellular Biochemistry Supplement 0(18C): 223, 1994

Lineages of oncogenic human papillomavirus types other than type 16 and 18 and risk for cervical intraepithelial neoplasia. Journal of the National Cancer Institute 106(10), 2014

Human papillomavirus 16 load and E2/E6 ratio in HPV16-positive women: biomarkers for cervical intraepithelial neoplasia >or=2 in a liquid-based cytology setting?. Cancer Epidemiology, Biomarkers and Prevention 18(11): 2992-2999, 2010

Prevalence of cervical infection by human papillomavirus and cervical intraepithelial neoplasia in HIV-positive and negative women. Revista Brasileira de Ginecologia E Obstetricia 37(4): 178-185, 2017

Incidence of Cervical Human Papillomavirus and Cervical Intraepithelial Neoplasia in Women with Positive and Negative HIV Status. Revista Brasileira de Ginecologia E Obstetricia 38(5): 231-238, 2017

Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical intraepithelial neoplasia and cervical infection in young Japanese women. Human Vaccines and Immunotherapeutics 10(7): 1781-1794, 2015