摘要
目的观察F基因型腮腺炎减毒活疫苗的急性毒性及长期毒性试验效果。方法取前期制备的F基因型腮腺炎减毒活疫苗进行大鼠急性毒性试验,之后进行临床症状监测及大体病理学检查;并采用恒河猴进行长期毒性试验,之后观察试验动物的临床症状,进行血液学、生化检测、CD4+、CD8+细胞比例检测、病毒血症检测、病毒在组织器官的分布检测以及病理检查。结果急性毒性试验表明给予大鼠相当于人用剂量的1200倍剂量时,无论是临床症状监测还是大体病理学检查,均无明显异常;而长期毒性试验结果表明,恒河猴3次免疫8倍人用剂量时,疫苗对动物临床症状、血液学和血清生化指标无明显影响,CD4+、CD8+细胞比值亦无明显改变,动物的血液及组织器官中均未检出腮腺炎病毒RNA,各组织器官未见明显大体病理学改变。结论 F基因型腮腺炎减毒活疫苗的急性毒性试验及长期毒性试验均无明显异常,充分验证了疫苗的安全性,从而为疫苗进入临床试验提供了数据支持并奠定了基础。
Objective To observe the effect of acute toxicity and long - term toxicity test for F genotype live attenuated mumps vac- cine. Methods Acute toxicity test was taken in rats with the pre - preparation of F genotype live attenuated mumps vaccine. Then we monitored the clinical symptoms and examined the general pathology. Longterm toxicity test was carried out with rhesus monkeys, and the clinical symptoms, hematological, biochemical detection, CD4 ＋ , CD8 ＋ cell ratio, viremia detection, virus distribution of tissues and organs and pathology detection were studied. Results Acute toxicity test showed there were no obvious abnormalities whether in clinical symptoms or in gross pathological examination when the rats were given the dose equivalent to 1200 times the human dose. Long - term tox- icity test showed that when third immunized the rhesus monkeys with the dose equivalent to 8 times of the human dose, there was no signif- icant effect against animal clinical symptoms, hematology and serum biochemical detection, and there was no obvious change in CD4 ＋ and CD8 ＋ cell ratio. Mumps virus RNA was not detected in blood, tissues and organs, as well as there were no significant general pathological changes in tissues and organs. Conclusion The safety of the F genotype mumps live attenuated vaccine was fully verified when there were no significantly abnormal issues in the acute toxicity test and long - term toxicity tests, which provided data and laid the foundation for the vaccine entering the clinical trials.
出处
《医学研究杂志》
2013年第5期30-34,共5页
Journal of Medical Research
基金
国家"863"计划项目(2012AA02A404)
"十二五"重大新药创制国家科技重大专项基金资助项目(2012ZX09101319)
国家科技重大专项基金资助项目(2009ZX10004-308)
云南省应用基础研究重点项目(2008CC018)
