食蟹猴肌肉注射冻干人用狂犬病疫苗(Vero细胞)的长期毒性  

Long-term toxicity of freeze-dried rabies vaccine for human use(Vero cells)for intramuscular injection in machins

作　　者：苗丽[1] 丁丽丽[1] 李春艳[1] 赵博[1] 崔文广[1] 苑志刚[1] 刘岩[1] 杨屹[1] 

机构地区：[1]长春生物制品研究所有限责任公司疫苗研究室,吉林长春130062

出　　处：《中国生物制品学杂志》2014年第11期1369-1374,共6页Chinese Journal of Biologicals

摘　　要：目的评价食蟹猴反复肌肉注射冻干人用狂犬病疫苗(Vero细胞)的长期毒性。方法采用区段随机分组法,将24只食蟹猴分为阴性对照组、辅料对照组、冻干人用狂犬病疫苗低(1剂/次)、高(5剂/次)剂量组(分别为临床人用剂量的1和5倍),每组6只,雌雄各半,各组均于第0、3、7、14、28和42 d经肌肉注射各免疫1次,停药后进行一般临床观察及体重、体温、心电图、眼科、血液学指标、血液生化及电解质指标、尿液指标、免疫指标、骨髓涂片、脏器及组织病理学改变观察,连续观察4周。结果试验期间各组动物一般状况良好,注射部位肉眼观察无异常;体重、体温、心电图、血细胞计数、凝血功能、血生化、眼科检查、尿常规、外周血T淋巴细胞亚群分布、血清细胞因子IL-2和IFNγ水平、骨髓组织、脏器系数等均未见有毒理学意义的规律性改变;疫苗低、高剂量组动物免疫后血清抗狂犬病病毒特异性抗体水平明显升高,均可产生具有保护作用(大于0.5 IU/ml)的中和抗体;辅料对照组和疫苗低、高剂量组部分动物注射局部可见轻微刺激性改变,4周恢复期结束时,局部刺激性反应消退。结论冻干人用狂犬病疫苗(Vero细胞)5剂/次(临床拟用剂量的5倍)以下为无毒性反应剂量,临床需重点关注注射部位局部刺激性反应。Objective To evaluate the long-term toxicity of freeze-dried rabies vaccine（Vero cells） for human use in machins after repeat intramuscular injection. Methods Twenty-four machins were randomly divided into negative control,auxiliary material control,as well as low（1 dose / time）and high（5 doses / time）dose groups,six for each,with equal genders. The low and high doses were 1 and 5 times of those for human use in clinic respectively. The machins in each group were injected i.m. on days 0,3,7,14,28 and 42 respectively,and observed for 4 weeks after the last injection for general clinical indexes,bodyweight,body temperature,electrocardiogram（ECG）,ophthalmology,hematology,blood biochemistry,electrolyte index,urine index,immune index,bone marrow smear as well as pathological changes in organs and tissues. Results The general state of animals in various groups were normal,while no visual adverse reactions were observed in injection site. No regular changes of toxicological significance were observed in bodyweight,body temperature,ECG,blood cell count,coagulation function,blood biochemistry,ophthalmology,routine urine examination,peripheral blood T lymphocyte subset distribution,serum IL-2 and IFNγ levels,bone marrow or organ coefficient. The serum specific antibody level against rabies virus increased significantly in low and high dose groups,while protective（more than 0. 5 IU / ml）neutralizing antibodies were induced. Mild irritant changes in injection site were observed in auxiliary material control as well as low and high dose groups,which resolved after a convalescent period of 4weeks. Conclusion The non-toxic reaction dosage of freeze-dried rabies vaccine for human use was less than 5 doses /time,while local irritant reaction in injection site should be noted in clinic.

关 键 词：狂犬病疫苗 VERO细胞 长期毒性 食蟹猴 

分 类 号：R373.9[医药卫生—病原生物学] R392.33[医药卫生—基础医学]