治疗型HBV DNA疫苗肌注-电转染法免疫恒河猴的效果及安全性观察

为观察肌注—电转染法接种治疗型HBVDNA疫苗对恒河猴的免疫效果，对健康恒河猴采用肌注—电转染法接种治疗型HBV DNA疫苗，剂量分别为0．2mg／只、1mg／只和2mg／只；前3次给药时间间隔1个月，主要观察免疫效果；此后6次给药为每天1次，观察重复给药的安全性。结果显示肌注—电转染法接种疫苗后，不同剂量组均可有效诱导恒河猴产生HBsAg特异性抗体(抗—HBs)；重复给药未见明显的各系统毒副反应及血液学和血生化异常，血清抗核抗体(ANA)阴性。表明治疗型HBV DNA疫苗用肌注—电转染法免疫可显著增强恒河猴的免疫效果；多次重复接种该疫苗未见恒河猴的毒性反应，疫苗具有安全性。

INDUCTION OF IMMUNE RESPONSES AND SAFETY PROFILES IN RHESUS MACAQUES IMMUNIZED WITH THE THERAPEUTIC DNA VACCINE AGAINST HEPATITIS B VIRUS

To evaluate the immune response and safety of the therapeutic DNA vaccine against the hepatitis B virus in rhesus macaques immunized by intramuscular injection of therapeutic DNA vaccine combined with electroporation. HBV DNA vaccine was administered to rhesus macaques by repeated intramuscular injections combined with electroporation in doses of 0 2,1 and 2mg, monthly for three consecutive months. The anti HBs antibody level was used to evaluate the efficacy of induction of humoral immunity. After that, the vaccine was intramuscularly injected daily in the same dose for six days to evaluate its safety. It was found that immunization with the therapeutic DNA vaccine against hepatitis B virus by means of intramuscular injections combined with electroporation induced a strong and specific anti HBs humoral immune response in rhesus macaques.Nine repeated intramuscular injections of the vaccine did not show adverse effects on behaviors, hematology, blood chemistry, and histopathology. No evidences of autoimmune mediated pathology and anti nuclear antibodies were observed in the rhesus macaques. These results suggested that electroporation significantly improves the efficacy of the therapeutic HBV DNA vaccine in rhesus macaques.The vaccine is safe and well tolerated.