MVA E2 recombinant vaccine in the treatment of human papillomavirus infection in men presenting intraurethral flat condyloma - A phase I/II study
MVA E2 recombinant vaccine in the treatment of human papillomavirus infection in men presenting intraurethral flat condyloma - A phase I/II study
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DOI：
10.2165/00063030-200721010-00006
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发表时间：
2007-01-01
期刊：
影响因子：
6.8
通讯作者：
Rosales, Ricardo
中科院分区：
文献类型：
--
作者：
Albarran y Carvajal, Antonio;de la Garza, Alfonso;Rosales, Ricardo
背景：人乳头瘤病毒（HPV）是尖锐湿疣和宫颈癌的病原体。在墨西哥，宫颈癌的死亡率极高，统计数据显示，自1990年以来，死亡人数不断增加。尖锐湿疣和阴茎癌是男性最常见的病变;男性膀胱癌和前列腺癌也与HPV的存在有关。由于FIPV是通过性交传播的，为了消除人群中的病毒，治疗双方都是必要的。解决这一问题的方法包括预防性疫苗，如Gardasil（R）和治疗性疫苗，以治疗男性和女性的感染。这将是唯一的方法，以减少由于这种malignancy.Patients和方法的死亡人数：我们进行了I/II期临床试验，以评估潜在的使用重组牛痘病毒疫苗MVA E2（由修改后的牛痘病毒安卡拉[MVA]表达的E2基因的牛乳头瘤病毒）治疗扁平湿疣病变与致癌HPV在男性。对50例扁平型尖锐湿疣男性患者采用MVA E2治疗性疫苗或氟尿嘧啶（5-氟尿嘧啶）治疗。30名男性接受了治疗性疫苗，每剂共106个病毒颗粒，每周一次直接注射到尿道中，持续4周。20名对照患者在4周内每周两次直接进入尿道接受5%氟尿嘧啶1 mL治疗。通过阴道镜检查和组织学分析监测病变的减少或乳头状瘤病毒感染的消失。通过测量针对MVA E2病毒的抗体和通过分析针对携带致癌乳头瘤病毒的癌细胞的淋巴细胞细胞毒性活性来确定MVA E2处理后的免疫应答。HPV的存在是由杂交捕获（R）method.Results：二十八30例患者显示没有病变或乳头状瘤病毒的存在，诊断阴道镜和刷组织学检查后，4周的MVA E2治疗。所有患者尿道扁平湿疣完全消失，包皮上无醋酸白色斑点。在另外两名患者中，醋酸白斑和扁平湿疣没有减少。所有患者都产生了针对MVA E2疫苗和E2蛋白的抗体，并产生了针对乳头状瘤转化细胞的特异性细胞毒性反应。MVA E2治疗组未检出病毒DNA，对照组20例中13例无病变。其中3名患者在治疗3个月后出现病变复发，没有患者产生针对癌细胞的特异性抗体。相比之下，接受MVA E2治疗的患者在治疗1年后未显示任何病变复发。结论：MVA E2治疗性疫苗能有效刺激免疫系统抵抗乳头瘤病毒，并能使扁平湿疣消退。
Background: 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 FIPV 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 (R), 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.Patients and methods: 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 106 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 1 mL 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 (R) method.Results: 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 patients were free of lesions. Three of these patients had recurrence of lesions after 3 months of treatment and none of the patients developed specific antibodies against cancer cells. In contrast, patients treated with MVA E2 did not show any recurrence of lesions after I year of treatment. In addition, none of the patients had local or systemic adverse effects according to the WHO classification 1-4.Conclusions: Therapeutic vaccination with MVA E2 proved to be very effective in stimulating the immune system against papillomavirus, and in generating regression of flat condyloma lesions in men.