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按照《中华人民共和国药典(三部)》(2010年版)及WHO的相关要求,部分疫苗需定期进行猴体的神经毒力试验(NVT),以考察疫苗的毒种是否具有神经毒力及一定的免疫原性。主要试验方法:(1)动物筛选,除常规血液学、生化指标外,特别需检测证明其不含同类型病毒的中和抗体;(2)给药途径主要包括脑内的丘脑、额叶、小脑延髓注射及脊髓注射等。脑内注射特别需注意给药部位准确,可采用脑定位仪或磁共振扫描(MRI)检测注射部位检查是否能看到针迹,确定注射部位。(3)观察指标。动物死亡或濒死状态、一般状况,需重点观察神经症状,对可能出现的神经症状进行评级打分;血液学、血生化重点观察肝功能指标;猴血清内病毒抗体;组织病理学检查,需重点观察注射部位、脑或脊髓组织。神经毒力试验作为减毒活疫苗鉴定的常用试验,也是创新类疫苗制品的临床前安全评价试验之一。猴体神经毒力试验花费较高,给药操作带来的风险较大。但猴与人在生物学上具有高度的相似性,故本试验仍作为临床前安全性评价的重要参考。
According to the “People’s Republic of China Pharmacopoeia (2010)” and the relevant requirements of WHO, some vaccines need to carry out regular neurotoxicity test (NVT) of monkeys in order to investigate the vaccine virulence is neurotoxic and certain Immunogenicity. The main test methods: (1) animal screening, in addition to conventional hematology, biochemical indicators, in particular, need to test to prove that it does not contain the same type of virus neutralizing antibodies; (2) route of administration include the thalamus, frontal lobe, Medulla oblongata injection and spinal injection. Intracranial injection special attention to the site of administration is accurate, the brain locator or magnetic resonance imaging (MRI) can be used to detect whether the injection site can see the stitches and determine the injection site. (3) observation index. Animal death or dying state, the general situation, the need to focus on the observation of neurological symptoms, neurological symptoms may occur on the rating scale; hematology, blood biochemistry focus on the observation of liver function; monkey serum antibody; histopathological examination, the need to focus Observation of injection site, brain or spinal cord tissue. As a commonly used test for the identification of attenuated live vaccines, the neurotoxicity test is also one of the pre-clinical safety evaluation tests for innovative vaccine products. The higher cost of the test of neurotoxicity in monkeys and the higher risk of drug administration. However, monkeys and humans have a high degree of biological similarity, so this test is still an important reference for pre-clinical safety evaluation.