Residual enzymatic activity of the tetanus toxin light chain present in tetanus toxoid batches used for vaccine production
Residual enzymatic activity of the tetanus toxin light chain present in tetanus toxoid batches used for vaccine production
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DOI：
10.1016/j.vaccine.2008.05.014
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发表时间：
2008-07-23
期刊：
影响因子：
5.5
通讯作者：
Kraemer, B.
中科院分区：
文献类型：
--
作者：
Behrensdorf-Nicol, H. A.;Kegel, B.;Kraemer, B.
破伤风神经毒素 (TeNT) 的轻链是一种锌依赖性金属蛋白酶，可特异性裂解突触小泡蛋白 synaptobrevin。破伤风毒性的这一关键机制会导致抑制性神经递质释放受阻。我们最近报道了一种高度灵敏的内肽酶检测方法的开发，用于基于这种蛋白水解特征的活性 TeNT 的体外特异性检测。使用这种方法，我们可以证明用于生产破伤风疫苗的甲醛灭活 TeNT 制剂（类毒素）含有较高的残留突触短蛋白裂解活性。在从多家疫苗制造商获得的许多破伤风类毒素批次中检测到了这种活性，这些疫苗在强制性动物试验中没有表现出任何体内毒性。酶活性可归因于游离 TeNT 轻链的存在，其功能并未受到甲醛处理的限制，但缺乏进入体内神经元所需的功能性重链。据我们所知，这是第一份描述破伤风类毒素残留蛋白水解活性的报告。 (c) 2008 Elsevier Ltd. 保留所有权利。
The light chain of tetanus neurotoxin (TeNT) is a zinc-dependent metalloprotease which specifically cleaves the synaptic vesicle protein synaptobrevin. This crucial mechanism of tetanus toxicity leads to a blockade of inhibitory neurotransmitter release. We recently reported the development of a highly sensitive endopeptidase assay for the specific in vitro detection of active TeNT based on this proteolytic feature. Using this method, we could show that formaldehyde-inactivated TeNT preparations (toxoids), which are used for the production of tetanus vaccines, contain a high residual synaptobrevin-cleaving activity. Such an activity was detected in numerous tetanus toxoid batches obtained from several vaccine manufacturers which did not display any in vivo toxicity in the obligatory animal tests. The enzymatic activity could be attributed to the presence of free TeNT light chains whose function had not been restrained by the formaldehyde treatment, but which lack the functional heavy chain necessary for entering neurons in vivo. To our knowledge, this is the first report describing a residual proteolytic activity in tetanus toxoids. (c) 2008 Elsevier Ltd. All rights reserved.