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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: To observe the toxicity and severity of SD vaccine induced by repeated injections of HCV. Methods: SD rats were randomly divided into two groups: low dose (500μg / kg) and low dose (1500μg / kg) and vehicle control group. The same satellite group was used for the detection of specific antibodies. Each group was given subcutaneous Injection 1, the end of the recovery observed for 4 weeks. Results: The animals in each group were generally in good condition during the administration period. No abnormalities were observed in the naked eye at the injection site. No significant abnormalities were found in food intake, body weight and body temperature. The serum levels of HCV specific antibodies in the two groups of low and high dose groups were significantly increased, and increased with the prolongation of immunization time (especially in high dose female mice). The performance of the two groups after administration were significantly higher than the high dose (1500μg / kg) group, mainly TP, ALB decreased slightly, NE% slightly increased, LY% slightly decreased, the injection site of the skin showed varying degrees of subcutaneous acute inflammation Response, there is a dose-effect trend, male rats brain, kidney coefficient and epididymal weight and coefficient of micro decrease, but after stopping can be restored, no significant delay in toxicity. Conclusions: The new vaccine dose of 500μg / kg (299.4 times of the recommended clinical dose and 48.5 times of the equivalent dose of the rat) is the non-toxic reaction dose. The clinical need to focus on the acute subcutaneous tissue inflammation at the injection site, Pay attention to white blood cells and their classification and TP, ALB changes.