水痘减毒活疫苗(SV-1细胞)的大鼠长期毒性试验  

Long-term toxicity test on live attenuated varicella vaccine(SV-1 cells)in rats

作　　者：杨利伟 栾春芳 干玲玲 王琳[2] 孟凡红 黄金凤 YANG L-wei LUAN Chun-fang GAN Ling-ling WANG Lin MENG Fan-hong HUANG Jin-feng(Sinovac （ Dalian ） Vaccine Technology Co., Ltd., Dalian 116620, Liaoning Province, China)

机构地区：[1]科兴(大连)疫苗技术有限公司,辽宁大连116620 [2]北京科兴生物制品有限公司,北京100085

出　　处：《中国生物制品学杂志》2017年第1期5-10,共6页Chinese Journal of Biologicals

摘　　要：目的观察SD大鼠注射水痘减毒活疫苗(SV-1细胞)后可能出现的毒性反应、毒性反应的恢复情况及可能出现的延迟性毒性反应。方法将SD大鼠随机分为8组,1~4组(主试验组)分为阴性对照组(生理盐水,2.5 ml/只)、细胞基质对照组(SV-1细胞基质,2.5 ml/只)、疫苗低剂量组(水痘减毒活疫苗1剂)和疫苗高剂量组(水痘减毒活疫苗5剂),每组30只;5~8组(卫星组)分组同1~4组,每组10只。均经大鼠颈背部皮下单点注射,每2周注射1次,连续注射3次,末次免疫后6周为恢复期。试验期间进行一般临床观察、体重、食量、体温、眼科、血细胞计数、凝血功能、血液生化、免疫指标、大体解剖观察、主要脏器称重、组织病理学等检查。结果试验期间,主试验组各组动物一般状况良好,各项指标检测均未见有毒理学意义的规律性改变,且动物脏器重量均未见与疫苗相关的明显改变,各组织脏器大体解剖观察均未见明显与给药相关的毒性病理学改变,注射局部组织未见明显与疫苗相关的刺激性反应;卫星组大鼠免疫前血清抗体均为阴性,末次免疫后2周,阴性对照组和细胞基质组抗体检测结果均为阴性,低剂量组和高剂量组抗体阳转率100%,抗体几何平均滴度(GMT)分别为1∶73.5和1∶111.4,仅有部分大鼠可检测到分泌IFNγ的T淋巴细胞。结论水痘减毒活疫苗(SV-1细胞)经大鼠长期毒性试验未见明显毒性反应,初步证实该疫苗具有良好的安全性及有效性。Objective To observe the possible toxic reactions and their convalescence as well as the potential delayed toxic reactions in SD rats after immunization with live attenuated varicella vaccine. Methods SD rats were randomly divided into eight groups. Groups 1 ~ 4 consisted of 30 rats, while groups 5 ~ 8 consisted of 10 rats. Groups 1 and 5 were served as negative control（physiological saline, 2. 5 ml）, while groups 2 and 6 as cell matrix control（SV-1 cell matrix,2. 5 ml）, groups 3 and 7 as low dose vaccine（one dose of live attenuated varicella vaccine）, and groups 4 and 8 as high dose vaccine（five doses of vaccine）groups. All the rats were injected s.c. in a single site of neck back, every 2 weeks for3 times. The time duration within 6 weeks after the last immunization was served as the convalescent period, in which the general clinical index, bodyweight, appetite, body temperature, ophthalmology, blood cell count, blood coagulation function, blood biochemistry and immune index were measured, while gross anatomic observation, main viscera weighing and histopathological examination were carried out. Results The general state of animals in groups 1 ~ 4 were normal,while no regular changes of toxicological significance were observed in various indexes. Gross anatomic observation showed no obvious change associated with immunization in toxicologic pathology of various tissues and organs, and no obvious vaccine-associated stimulating response in injection site. All the serum antibodies in groups 5 ~ 8 were negative before immunization. However, the serum antibodies in groups 5 and 6 were negative 2 weeks after the last immunization,while the antibody positive rates in groups 7 and 8 were 100%, and the GMTs were 1 ∶ 73. 5 and 1 ∶ 111. 4 respectively.The T lymphocytes secreting IFNγ were detected in partial rats. Conclusion Long-term toxicity test in rats showed no obvious toxic reaction of live attenuated varicella vaccine（SV-1 cells）, indicating good safety and effectiveness.

关 键 词：水痘减毒活疫苗 长期毒性试验 

分 类 号：R373.12[医药卫生—病原生物学] R392-33[医药卫生—基础医学]