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目的初步评价以阳离子脂质体二甲基三十六烷基铵(dimo-thylidioctyl ammonium bro-mide,DDA)、聚肌胞苷酸(Poly I∶C)及胆固醇复合佐剂(简称为DPC)为佐剂的结核融合蛋白ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-Rv2626c(LT70)亚单位疫苗的安全性。方法急性毒性试验:分别将低剂量与高剂量(分别相当于人用剂量的10 000和40 000倍)的LT70-DPC结核亚单位疫苗经皮下、腹腔两种途径免疫小鼠,观察小鼠毒性反应、死亡情况及体重变化等,同时推算小鼠对LT70-DPC亚单位疫苗的最大耐受剂量(maximum tolerated dose,MTD);异常毒性试验:将小鼠和豚鼠分别经腹腔注射LT70-DPC结核亚单位疫苗,观察动物异常反应、死亡情况及体重变化等;全身过敏试验:豚鼠经LT70-DPC结核亚单位疫苗免疫后,经相应疫苗静脉攻击,观察豚鼠过敏反应。结果急性毒性试验:皮下及腹腔注射后14 d内均未见小鼠的异常反应和死亡,体重均增加,小鼠对该疫苗的MTD为:LT70蛋白>6 600μg/kg,DDA>166 600μg/kg,Poly I∶C>33 200μg/kg,胆固醇>50 600μg/kg;异常毒性试验:注射后7 d内,小鼠及豚鼠全部健存,均未出现异常症状,体重增加;全身过敏试验:攻击后1 h内,豚鼠均未出现过敏反应。结论 LT70-DPC结核亚单位疫苗具有良好的安全性。
OBJECTIVE: To evaluate the effects of cationic liposomes containing dimodial thioidyl ammonium bromate (DDA), poly I (C) and cholesterol complex adjuvant (DPC) Adjuvanted tuberculosis fusion protein ESAT6-Ag85B-MPT64 (190-198) -Mtb8.4-Rv2626c (LT70) subunit vaccine. Methods Acute Toxicity Test: The mice were immunized subcutaneously with the LT70-DPC tuberculosis subunit vaccine at low dose and high dose (corresponding to 10,000 and 40,000 times the human dose respectively) Response, death and body weight changes, and calculate the maximum tolerated dose (MTD) of LT70-DPC subunit vaccine in mice. Abnormal toxicity test: mice and guinea pigs were injected intraperitoneally with LT70-DPC tuberculosis Subunit vaccine, observation of animal abnormal response, death and body weight changes; systemic allergy test: Guinea pigs after LT70-DPC tuberculosis subunit vaccine immunization, the corresponding vaccine intravenous challenge to observe the guinea pig anaphylaxis. Results Acute toxicity test showed no abnormal reaction and death in mice and increased body weight within 14 days after subcutaneous and intraperitoneal injection. The MTD of mice with this vaccine was: 6 600 μg / kg for LT70, 166 600 μg / kg, Poly I: C> 200 mg / kg, and Cholesterol> 50 600 μg / kg; Abnormal toxicity test: All mice and guinea pigs survived within 7 days after injection. No abnormal symptoms and weight gain were observed. Within 1 h after challenge, no guinea pig allergic reaction. Conclusion LT70-DPC tuberculosis subunit vaccine has good safety.