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首页> 外文期刊>Vaccine >Characterization of the carbohydrate binding and ADP-ribosyltransferase activities of chemically detoxified pertussis toxins.
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Characterization of the carbohydrate binding and ADP-ribosyltransferase activities of chemically detoxified pertussis toxins.

机译:化学解毒的百日咳毒素的碳水化合物结合和ADP-核糖基转移酶活性的表征。

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摘要

Pertussis toxin (PTx) is an essential component of the acellular pertussis (aP) vaccine. However, because PTx in its native form is considered too toxic for human vaccine use, it must be inactivated into a stable, nontoxic form by treatment with chemical detoxifying agents or by genetic modification. Therefore, testing for the residual PTx in the aP vaccine is a major quality control step for vaccine manufacturers and regulatory authorities. The histamine sensitization test is currently the standard safety test method for all aP vaccines, regardless of the vaccine formula or the detoxification process, except for those with genetically modified PTx. However, test result variability and ethical concerns regarding animal use necessitate an alternative method. In vitro assays based on the biochemical properties of PTx have been considered as potential alternatives to the histamine sensitization test. In this study, the suitability of assays based on the ADP-ribosyltransferase and carbohydrate binding activities of PTx was assessed for PTx after treatment with formaldehyde, glutaraldehyde or both denaturants in sequence. The results indicated a distinctive pattern of the biochemical activities depending on the detoxification methods and storage conditions. These results suggest that although a more careful study is needed, these in vitro biochemical assays can be considered potential alternatives to the histamine sensitization test, as they might provide more specific safety information of aP vaccines
机译:百日咳毒素(PTx)是脱细胞百日咳(aP)疫苗的重要组成部分。但是,由于天然形式的PTx被认为对于人类疫苗使用而言毒性太大,因此必须通过化学解毒剂处理或通过基因修饰将其灭活为稳定的无毒形式。因此,对aP疫苗中的残留PTx进行测试是疫苗制造商和监管机构的主要质量控制步骤。目前,组胺敏化测试是所有aP疫苗的标准安全性测试方法,而不论疫苗配方或排毒过程如何,除了带有基因修饰的PTx的那些。但是,测试结果的变异性和与动物使用有关的道德考量需要另一种方法。基于PTx的生化特性的体外测定已被认为是组胺敏化试验的潜在替代方法。在这项研究中,按顺序用甲醛,戊二醛或两种变性剂处理后,评估了基于PTx的ADP-核糖基转移酶和碳水化合物结合活性的分析的适用性。结果表明取决于排毒方法和储存条件的生化活性的独特模式。这些结果表明,尽管需要进行更仔细的研究,但这些体外生化分析可能被认为是组胺敏化试验的潜在替代方法,因为它们可能提供aP疫苗的更具体的安全性信息。

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