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首页> 外文期刊>Laboratory Animal Science >DEVELOPMENT OF A NEUROVIRULENT TESTING SYSTEM FOR ORAL POLIOVIRUS VACCINE WITH TRANSGENIC MICE
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DEVELOPMENT OF A NEUROVIRULENT TESTING SYSTEM FOR ORAL POLIOVIRUS VACCINE WITH TRANSGENIC MICE

机译：转基因小鼠口腔脊髓灰质炎疫苗神经毒性测试系统的研制

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摘要

Because only primates are susceptible to polioviruses, the neurovirulent safety and consistency of oral poliovirus vaccine (OPV) were assayed in the monkey neurovirulence test, After the development of transgenic (Tg) mice carrying the gene for human poliovirus receptor (PVR), the suitability of these mice to replace monkeys for OPV testing was evaluated, Two lines of Tg mice, TgPVR1 and TgPVR21, were tested, The TgPVR21 mice, inoculated in the spinal cord, were as sensitive as monkeys in discriminating between type-3 and type-2 OPV lots that had passed and those that had failed the monkey neurovirulence test, Results of the new molecular assay by polymerase chain reaction and restriction enzyme cleavage indicated that each OPV lot contained minuscule amounts of neurovirulent revertants in the viral genome. All type-3 OPV lots that failed the monkey neurovirulence test had higher percentages of 472-C revertants than did lots that passed this test, Analysis of multiple type-3 OPV lots also indicated a good correlation between the contents of 472-C revertants and results of the TgPVR2 mouse test. An overview of a significant set of data suggests that the TgPVR21 mouse model is suitable for the evaluation of type-3 and type-2 OPV. The necessity of the TgPVR mouse test for the neurovirulence of type-1 OPV, which is the most stable of the three Sabin strains, is under consideration.
机译：由于只有灵长类动物对脊髓灰质炎病毒敏感，因此在猴子神经毒性试验中测定了口服脊髓灰质炎病毒疫苗（OPV）的神经毒性安全性和一致性。在携带人类脊髓灰质炎病毒受体（PVR）基因的转基因（Tg）小鼠发育后，评估了这些小鼠中替代猴子进行OPV测试的情况，测试了两行Tg小鼠TgPVR1和TgPVR21，接种在脊髓中的TgPVR21小鼠与猴子一样敏感，可以区分3型和2型通过和未通过猴子神经毒性测试的OPV批次，通过聚合酶链反应和限制性内切酶裂解的新分子分析结果表明，每个OPV批次在病毒基因组中均含有微量的神经毒性回复剂。所有未通过猴子神经毒性测试的3型OPV批次中的472-C恢复子百分率均高于通过该测试的批次。对多个3型OPV批次的分析还表明472-C恢复子含量与TgPVR2鼠标测试的结果。对大量数据的概述表明，TgPVR21小鼠模型适用于3型和2型OPV评估。 TgPVR小鼠测试对于三种Sabin菌株中最稳定的1型OPV的神经毒性的必要性正在考虑中。

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