治疗性乙型肝炎疫苗长期毒性试验

目的：根据我国相关法规,开展治疗性乙肝疫苗的长期毒性试验.方法：将治疗性乙肝疫苗以高、中、低三个剂量经皮下注射食蟹猴,另以等体积生理盐水作为空白对照,每天给药1次,连续21 d,停药后继续观察4周.以血常规、尿常规、血生化、血清抗体和补体、病理学等为观察指标.结果：各组动物外观、行为活动未见异常,未见死亡;试验组动物对受试疫苗均产生免疫应答,血清中可检测到相应抗体;高剂量治疗性乙肝疫苗对食蟹猴肝、肾功能指标有一定影响,停药后可恢复;未见明显的迟发性毒性反应.结论：治疗性乙型肝炎疫苗安全性良好,对食蟹猴的最大无毒作用剂量为21μg·kg-1,约为人临床拟用剂量的21倍,以体表面积计,约为单次人临床拟用量的8倍.

Long-term Toxicity of Therapeutic Hepatitis B Vaccine

Objective： To observe long-term toxicity of therapeutic hepatitis B vaccine in eynomolgus monkeys based on regulations. Method： Cynomolgus monkeys were treated with therapeutic hepatitis B vaccine at high dose, medium dose and low dose by subcutaneous injection, once a day for 21 days, and in the control group, cynomolgus monkeys were injected with the same volume of sterilized normal saline solution. After treatment, the animals were observed continuously for 4 weeks. Parameters including haematology, u- rine, biochemistry ,immunology and pathology were collected. Result： The appearance and behavior of cynomolgus monkeys in each group were not abnormal, all animals were alive. The humoral immune response to therapeutic hepatitis B vaccine was observed in all the three treatment groups,i, e,hepatitis B surface antibody （HBsAb） were found in their serum; minor hepatic and renal dysfunction was observed in high dose group in the treatment period, but the dysfunction was reversible after treatment, delayed toxicity was not found in each group. Conclusion： Therapeutic hepatitis B vaccine might be safe for clinical use, the maximum non-toxic dosage is 21 μg· kg^-1 for cynomolgus monkeys, which amounts to 21-fold of human clinical dosage ;if the dosage is calculated according to body surface,which equals to 8-fold of human clinical dosage.