HCV新型抗原疫苗大鼠长期毒性试验研究

HCV new antigen vaccine rats long-term toxicity test research

目的:观察重复注射给予SD大鼠HCV新型抗原疫苗所产生的毒性反应及其严重程度。方法:SD大鼠随机分为500μg/kg、1500μg/kg低、高两个剂量组和溶媒对照组,同设卫星组用于特异性抗体检测,各组于给药0、2、4周皮下注射1次,给药结束恢复性观察4周。结果:给药期间各组动物一般状况良好,注射部位肉眼观察无异常;摄食量、体重、体温无明显异常。低、高两个剂量组大鼠免疫后的血清HCV特异性抗体水平明显升高,随免疫时间延长呈上升趋势(高剂量雌鼠较明显)。两组给药后的各表现均以高剂量(1500μg/kg)组较明显,主要为TP、ALB略微降低,NE%略升高、LY%略降低,注射部位皮肤出现不同程度皮下组织急性炎症反应,有一定剂量-效应趋势,雄鼠脑、肾系数和附睾重量及系数微减少,但停药后均可恢复,未见明显延迟毒性。结论:HCV新型抗原疫苗500μg/kg(为推荐临床拟用剂量的299.4倍,大鼠等效剂量的48.5倍)以下为无毒性反应剂量;临床需重点关注注射部位皮肤局部皮下组织急性炎症反应,注意白细胞及其分类和TP、ALB的变化情况。

Objective：Observation repeated injection to SD rats HCV new antigen vaccine produced by the toxic reaction and its serious degree.Methods：SD rats were randomly divided into 500μg/kg.bw low,1500μg/kg.bw high two dose group and solvent control group,with a satellite group used for specific antibody detection,in each group to medicine 0 w,2 w,4 w subcutaneous injection 1 time,the end to the medicine restorative observation 4 weeks.Results：During the drug group animal general situation is good,the injection site macroscopic observation no abnormalities;Food consumption,body weight,body temperature have no obvious abnormity.Low and high two dose group of rats after immune serum HCV specific antibody level increased significantly,with immune time extension shows ascendant trend（high dose pheromones is obvious）.Two groups after the administration performance are all with high dose（1500μg/kg.bw） group is more apparent,mainly for the TP,ALB slightly lower,NE % slightly raised,LY % slightly lower,injection site skin appear different degree subcutaneous tissue acute inflammatory reaction,have certain dose-effect trend,male brains,renal coefficient and epididymis weight and coefficient micro reduce,but after discontinuation of all can restore,did not see the apparent delay toxicity.Conclusion：HCV new antigen vaccine 500μg/kg.bw（recommended for clinical prove the dose of 299.4 times,rat equivalent dose of 48.5 times） the following is non-toxic reaction dose;Clinical need to focus on injection site skin local subcutaneous tissue acute inflammatory reaction,pay attention to white blood cells and its classification and TP,ALB changes.