乙肝核酸疫苗安全性的初步研究  

Evaluation of the long-term toxicity for hepatitis B nucleic acid vaccine

作　　者：佘佳红[1] 袁伯俊[1] 陆国才[1] 胡振林[2] 陈黛影[1] 

机构地区：[1]第二军医大学新药评价中心,上海200433 [2]第二军医大学医学遗传教研室,上海200433

出　　处：《中国新药杂志》2005年第9期1141-1144,共4页Chinese Journal of New Drugs

摘　　要：目的:研究乙肝核酸疫苗对小鼠和豚鼠的长期毒性。方法:健康小鼠和豚鼠分别按体重随机分为低、中、高剂量组(小鼠剂量分别为0·5,1·5,4·5mg·kg-1,豚鼠剂量分别为0·1,0·4,0·8mg·kg-1)和溶媒对照组。2种动物均每周后肢肌内注射2次,共8周。末次给药后24h和停药后30d分别测血液学、血液生化、病理检查和小鼠的各项免疫指标(包括IgG1和IgG2a亚型血清水平、血清抗核抗体、血清抗体总水平、γ-干扰素(IFN-γ)和白介素-4(IL-4)血清水平、外周血中各淋巴细胞亚群的分布情况和染色体整合检测)。结果:两种动物各剂量组的各项常规检测指标均未见有任何异常变化,与空白及溶媒对照组相比均无显著性差异。小鼠免疫指标未出现与治疗目的无关的改变。结论:受试疫苗在两种动物未观察到明显的生化、病理学、免疫学指标异常。小鼠和豚鼠肌内注射乙肝核酸疫苗的安全剂量分别为4·5和1·2mg·kg-1。Objective：To assess the long-term toxicity of hepatitis B nucleic acid vaccine （HBV DNA vaccine） in mice and guinea pigs. Methods： Mice and guinea pigs were randomly injected with the vaccine （low, medium and high doses）, solvent that was used to dissolve the vaccine or water alone twice per week for 8 weeks, respectively. The tested mice and guinea pigs were euthanized in 24 hours and 30 days, respectively, at the end of the 8-week course of treatment to assess their physical, histopathological and immune conditions. The blood tests included hematology, biochemistry, serum IgG1, IgG2a, IFN-γ ang IL-4 levels,serum antinuclear antibody,total serum antibody,and lymphocytes and chromosomal status.Results：No significant differences were observed in the vaccine and solvent groups compared with the water group for all of the examinations Conclusion：The nucleotide vaccine became no toxic to the mice and guinea pigs with a safe dose of 4.5 and 1.2mg·kg^-1,respectively.

关 键 词：乙肝核酸疫苗 小鼠 豚鼠 长期毒性 

分 类 号：R965.3[医药卫生—药理学] R512.62[医药卫生—药学]