冻干人用狂犬病疫苗(MRC-5细胞)非临床安全性研究

Non-clinical safety of freeze-dried rabies vaccine(MRC-5 cell) for human

目的 对冻干人用狂犬病疫苗(MRC-5细胞)进行全身主动过敏试验、肌肉刺激性、单次给药毒性和溶血性评价,以考察其安全性。方法 本研究起止时间为2014年3月至2016年10月。按照确定的工艺和质量标准,使用人二倍体细胞MRC-5培养狂犬病固定毒株,灭活、纯化后制备冻干人用狂犬病疫苗,质量检定合格后,用于开展全面的动物毒理试验。结果 在本试验条件下,含有人血白蛋白的赋形剂组、低剂量和高剂量疫苗组均会引起豚鼠过敏症状,第14和21天激发后病死率分别为0(0/6)、0(0/6)、16.67%(1/6)和33.33%(2/6)、50.00%(3/6)、33.33%(2/6),三组病死率差异无统计学意义(P>0.05),不含人血白蛋白的赋形剂组无过敏症状;单次或多次给药均不会引起家兔肌肉刺激性反应;最高剂量50 IU/kg时,均未见明显的ICR小鼠毒性反应;疫苗不会引起红细胞溶血和凝聚。结论 动物试验表明,冻干人用狂犬病疫苗(MRC-5细胞)显示出良好的安全性。

Objective To evaluate the safety of freeze-dried human rabies vaccine (MRC-5 cells) by performing active allergy test,muscle irritation evaluation,single administration toxicity and hemolytic.Methods The experimental study started and ended from March 2014 to October 2016.Following the established processes and quality standards,rabies virus fixed strain was cultured in human diploid MRC-5 cell line,and then was inactivated and purified for preparing the freeze-dried rabies vaccine.After passing the QC test,the vaccine was used for a comprehensive animal toxicology test.Results In this experiment,excipients group containing human albumin,low dose,and high dose vaccine groups caused guinea pig allergy symptoms,the mortality rates after challenge on the 14th and 21st days were 0 (0/6),0 (0/6),16.67%(1/6) and 33.33%(2/6),50.00%(3/6),33.33%(2/6),there was no significant difference in mortality among the triple groups (P>0.05),and the excipients group without human albumin had no allergic symptoms;single or multiple injections of the vaccine did not cause muscle irritation in rabbits;no significant ICR mouse toxicity was observed at the highest dose of 50 IU/kg;the vaccine did not cause red blood cell hemolysis and condensation.Conclusion Freeze-dried rabies vaccine(MRC-5 cell) for human shows good safety in animals.