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中国科学家李荣秀等在TNF疫苗研究方向取得创新性突破成果

2016-10-19 佚名 生物谷

TNF疫苗
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TNF-α生物抑制剂是最早于用于治疗类风湿关节炎的细胞因子靶点，并表现出显着的临床疗效，虽然TNF-α生物抑制剂在全球生物制剂的销售额一直保持领先地位，但TNF-α生物抑制剂的价格昂贵和抗-药物-抗体的副作用限制其广泛的使用，另一种比较好的替代方法TNF-α疫苗的研制工作尽管在前期的动物实验中显示了良好的效果，但在临床实验中却没有达到预期。TNF-α疫苗在临床前动物水平上表现出一定的效果，但在临床

TNF-α生物抑制剂是最早于用于治疗类风湿关节炎的细胞因子靶点，并表现出显着的临床疗效，虽然TNF-α生物抑制剂在全球生物制剂的销售额一直保持领先地位，但TNF-α生物抑制剂的价格昂贵和抗-药物-抗体的副作用限制其广泛的使用，另一种比较好的替代方法TNF-α疫苗的研制工作尽管在前期的动物实验中显示了良好的效果，但在临床实验中却没有达到预期。TNF-α疫苗在临床前动物水平上表现出一定的效果，但在临床实验中没有取得预期疗效。所以需要设计一个更有效的疫苗。该实验室李荣秀教授，张丽博士等人，将白喉毒素T结构域作为分子骨架蛋白设计、制备的TNF-α新型疫苗可以显着降低小鼠类风湿关节炎模型的发病率和发病严重程度。“这是我们首次报道的基于一个临床安全的载体蛋白、骨架蛋白的疫苗设计开发”本文的通讯作者李荣秀教授说道。李教授和他的同事假定将TNF-α的一个有效表位移植到改骨架蛋白上，可以降低TNF-α的本身的毒性，并增加最后疫苗的稳定性。李教授解释到：“白喉毒素的转膜结构域DTT，因其为纯粹的“α螺旋-环状”结构特征，并且拥有丰富的通用T辅助表位，可以协助自身蛋白打破免疫耐受，并且此种设计的蛋白疫苗可以在大肠杆菌中高效表达。”

研究人员在诱导了小鼠关节炎疾病模型后两周给与次TNF-α疫苗。发现基于白喉毒素T结构域（DTT）和TNF-α的表位的新型疫苗可以推迟关节炎发病15天，最终有90%的关节炎模型小鼠发病而DTT对照组仅有45%发病。接受TNF-α疫苗的在发病分数上最终可以降低8倍，这点也在组织切片中对骨侵蚀、滑膜炎症、炎性细胞浸润、软骨破坏的观察得到确认。

有趣的是，通过TNF-α疫苗免疫小鼠后可以刺激针对天然TNF-α的特异性抗体产生，并且大部分抗体为IgG1型抗体，预示着抗体类型发生转换。“令人意想不到的是，此疫苗激发的抗体滴度可以持续长达6个月，证明这种针对TNF-α靶点的疫苗的对慢性炎症疾病的一个明显优势”李教授解释道，“对于TNF-α疫苗来说这是一个显着的进步，因为针对TNF-α的抗体滴度一般都的很短暂的”。项目研究团队目前正在进行该疫苗的临床前研究工作并且希望此疫苗早日进入临床。

原始出处

Zhang L1, Wang J2, Xu A1, Zhong C1, Lu W3, Deng L4, Li R1,5.A Rationally Designed TNF-α Epitope-Scaffold Immunogen Induces Sustained Antibody Response and Alleviates Collagen-Induced Arthritis in Mice.PLoS One. 2016 Sep 22

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    2017-01-02 guihongzh

    #中国科学#

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    2016-10-21 lilianxiang

    #创新#

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    2016-10-21 snowpeakxu

    #TNF#

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    2016-10-21 12498e5fm15(暂无昵称)

    #中国科学家#

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