MVA E2 recombinant vaccine in the treatment of human papillomavirus infection in men presenting intraurethral flat condyloma: a phase I/II study

• Published in: BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy biopharmaceuticals, and gene therapy, 2007, Vol.21 (1), p.47-59
• Main Authors: Albarran Y Carvajal, Antonio, de la Garza, Alfonso, Cruz Quiroz, Benitez Jose Cecilio, Vazquez Zea, Eduardo, Díaz Estrada, Ismael, Mendez Fuentez, Ernesto, López Contreras, Mario, Andrade-Manzano, Alejandro, Padilla, Santiago, Varela, Axel Ramírez, Rosales, Ricardo
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Bovine papillomavirus; Condylomata Acuminata - therapy; DNA-Binding Proteins - immunology; Human papillomavirus; Humans; Male; Middle Aged; Molecular Sequence Data; Papillomaviridae - immunology; Papillomavirus; Papillomavirus Vaccines - adverse effects; Papillomavirus Vaccines - immunology; Papillomavirus Vaccines - therapeutic use; T-Lymphocytes, Cytotoxic - immunology; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - immunology; Vaccines, Synthetic - therapeutic use; Vaccinia virus; Vaccinia virus - genetics; Viral Proteins - immunology
• ISSN: 1173-8804
• DOI: 10.2165/00063030-200721010-00006

Human papillomavirus (HPV) is the etiologic agent for warts and cervical cancer. In Mexico, the death rate from cervical cancer is extremely high, and statistical data show that since 1990 the number of deaths is increasing. Condylomas and cancer of the penis are the most common lesions presented in men; bladder and prostate cancer in men are also associated with the presence of HPV. Since HPV is transmitted by sexual intercourse, treating both partners is necessary in order to eliminate the virus in the population. Approaches to this include preventative vaccines such as Gardasil, and therapeutic vaccines to treat established infections in both men and women. This will be the only way to decrease the numbers of deaths due to this malignancy. We conducted a phase I/II clinical trial to evaluate the potential use of the recombinant vaccinia viral vaccine MVA E2 (composed of modified vaccinia virus Ankara [MVA] expressing the E2 gene of bovine papillomavirus) to treat flat condyloma lesions associated with oncogenic HPV in men. Fifty male patients with flat condyloma lesions were treated with either MVA E2 therapeutic vaccine or fluorouracil (5-fluorouracil). Thirty men received the therapeutic vaccine, at a total of 10(6) virus particles per dose, administered directly into the urethra once every week over a 4-week period. Twenty control patients were treated with 5% fluorouracil 1mL twice weekly over a 4-week period directly into the urethra. Reduction of lesions or absence of papillomavirus infection was monitored by colposcopy and histologic analysis. The immune response after MVA E2 treatment was determined by measuring the antibodies against the MVA E2 virus and by analyzing the lymphocyte cytotoxic activity against cancer cells bearing oncogenic papillomavirus. Presence of papillomavirus was determined by the Hybrid Capture method. Twenty-eight of 30 patients showed no lesion or presence of papillomavirus as diagnosed by colposcopy and brush histologic examination after 4 weeks of MVA E2 treatment. These patients showed complete elimination of flat condyloma in the urethra and no acetowhite spots were detected over the prepuce. In two other patients the acetowhite spots and flat condyloma did not diminish. All patients developed antibodies against the MVA E2 vaccine and E2 protein, and generated a specific cytotoxic response against papilloma-transformed cells. Viral DNA was not detected in MVA E2-treated patients. In the control group, 13 of 20 patie