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PLoS Pathog:新皮肤癌疫苗在动物模型中效果显著

  1. 乳头瘤病毒
  2. 器官移植
  3. 多乳鼠
  4. 皮肤癌

来源:生物谷 2014-02-22 18:26

动物实验的结果显示新疫苗能够显著降低乳头瘤病毒相关的良性和恶性皮肤癌。

2014年2月23日讯 /生物谷BIOON/--器官移植过程中需要服用免疫抑制类药物,防止移植受体的免疫系统对移植器官产生排斥反应。而器官移植病人免疫系统功能被抑制后,乳头瘤病毒(Papillomaviruses)会趁虚而入,侵染正常皮肤,引起非黑色素瘤皮肤癌。该皮肤癌会大量生长,严重影响病人的生活质量。有研究称移植病人患该皮肤癌的概率是正常人的250倍。

位于海德堡的德国癌症研究中心的Frank Rosl博士带领研究团队为了帮助器官移植病人不患皮肤癌,构建了乳头瘤病毒疫苗。动物实验的结果显示该疫苗能够显著降低乳头瘤病毒相关的良性和恶性皮肤癌。

多乳鼠(multimammate mouse)是研究乳头瘤病毒的良好模式动物。该鼠能够模拟人类的感染过程。而且多乳鼠对乳头瘤病毒比人类还敏感,大多数小鼠会自发产生一些良性的皮肤癌。

科学家构建乳头瘤病毒疫苗,并将疫苗注射入多乳鼠体内。科学家发现该疫苗能够完全防止良性和恶性皮肤癌的出现。

科学家称,该疫苗并没有完全清除乳头瘤病毒,但是皮肤细胞中的病毒数量会显著降低,所以疫苗成功的"教会"了免疫系统识别该病毒。更重要的是在免疫抑制剂处理过的多乳鼠中同样有效。

科学家称,该研究是开发临床疫苗防止乳头瘤病毒诱发癌症的基础,器官移植病人尤其需要该疫苗。(生物谷Bioon.com)

doi: 10.1371/journal.ppat.1003924

Protective Vaccination against Papillomavirus-Induced Skin Tumors under Immunocompetent and Immunosuppressive Conditions: A Preclinical Study Using a Natural Outbred Animal Model

Sabrina E. Vinzón, Ilona Braspenning-Wesch, Martin Müller, Edward K. Geissler, Ingo Nindl, Hermann-Josef Grone, Kai Schafer, Frank Rosl

Certain cutaneous human papillomaviruses (HPVs), which are ubiquitous and acquired early during childhood, can cause a variety of skin tumors and are likely involved in the development of non-melanoma skin cancer, especially in immunosuppressed patients. Hence, the burden of these clinical manifestations demands for a prophylactic approach. To evaluate whether protective efficacy of a vaccine is potentially translatable to patients, we used the rodent Mastomys coucha that is naturally infected with Mastomys natalensis papillomavirus (MnPV). This skin type papillomavirus induces not only benign skin tumours, such as papillomas and keratoacanthomas, but also squamous cell carcinomas, thereby allowing a straightforward read-out for successful vaccination in a small immunocompetent laboratory animal. Here, we examined the efficacy of a virus-like particle (VLP)-based vaccine on either previously or newly established infections. VLPs raise a strong and long-lasting neutralizing antibody response that confers protection even under systemic long-term cyclosporine A treatment. Remarkably, the vaccine completely prevents the appearance of benign as well as malignant skin tumors. Protection involves the maintenance of a low viral load in the skin by an antibody-dependent prevention of virus spread. Our results provide first evidence that VLPs elicit an effective immune response in the skin under immunocompetent and immunosuppressed conditions in an outbred animal model, irrespective of the infection status at the time of vaccination. These findings provide the basis for the clinical development of potent vaccination strategies against cutaneous HPV infections and HPV-induced tumors, especially in patients awaiting organ transplantation.

 

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