以修饰的脂质体为佐剂的四价流感疫苗安全性研究  

Safety of Tetravalent Influenza Vaccines Adjuvanted with Modified Liposomes

作　　者：李漂 杨艾 张茜 刘晓琳 鲁卫东 LI Piao;YANG Ai;ZHANG Qian;LIU Xiaolin;LU Weidong(Yunnan Key Laboratory of Pharmacology for Natural Products,School of Pharmaceutical Science,Kunming Medical University,Kunming 650500,China)

机构地区：[1]昆明医科大学药学院,云南省天然药物药理重点实验室,昆明650500

出　　处：《中国药学杂志》2024年第21期1997-2002,共6页Chinese Pharmaceutical Journal

基　　金：云南省生物医药重大科研专项基金项目资助(2018ZF006)。

摘　　要：目的 考察以聚乙二醇6000(PEG6000)和阳离子[2,3-二油氧基丙基三-甲基氯化铵(DOTAP)∶1,2-二油酰基磷脂酰碱(DOPC)摩尔比4∶1]修饰的脂质体为佐剂的四价流感疫苗安全性。方法 将小鼠分为5组:PBS阴性对照组、空白中性脂质体组、PEG6000脂质体组、阳离子4∶1组、疫苗原液组,通过异常毒性实验、急性毒性实验、长期毒性实验,记录小鼠的一般行为、体质量、摄食量、脏器指数与形态、血液指标等对以PEG6000和阳离子修饰的脂质体为佐剂的四价流感疫苗进行安全性研究。结果 异常毒性实验:注射后7 d内,小鼠全部健存,均未出现异常症状,体质量增加;急性毒性实验:一次性腹腔注射0.5 mL(血凝素含量15μg),14 d内均未见小鼠的异常反应和死亡,体质量均增加,各项血液指标无异常;长期毒性实验:于0、14、28 d进行3次腹腔免疫0.2 mL(血凝素含量6μg),分别于急性期(最后一次免疫3 d后)和恢复期(最后1次免疫14 d后)分批处死小鼠,实验期间小鼠未见异常情况和死亡,体质量均增加,血常规和血液生化指标均属正常范围内波动,未发现与给药相关的毒性反应,病理组织检查脏器无病变。结论 以PEG6000和阳离子4∶1组(DOTAP∶DOPC摩尔比4∶1)修饰的脂质体为佐剂的四价流感疫苗具有较好的安全性。OBJECTIVE To investigate the safety of the tetravalent influenza vaccines adjuvanted with PEG6000 and cationic[2,3-dioleoxypropyltrimethylammonium chloride(DOTAP)∶1,2-dioleoyl phosphatidylcholine(DOPC)]-modified liposomes.METHODS Mice were divided into five groups∶PBS negative control group,blank neutral liposome group,PEG6000 liposome group,cationic 4∶1 liposome group,and vaccine stock solution group.Abnormal toxicity test,acute toxicity test,and long-term toxicity test were performed.The general behavior,body weight,food intaking,viscera index,morphology,and blood indexes of mice were recorded to evaluate the safety of the vaccines adjuvanted with PEG6000 and cationic-modified liposomes.RESULTS Abnormal toxicity test∶within 7 days after injection,all mice were alive with weight gaining and without abnormal symptoms.Acute toxicity test∶0.5 mL(hemagglutinin content 15μg)was injected intraperitoneally,and no abnormal reaction or death was observed within 14 d.Long-term toxicity test∶The mice were inoculated with 0.2 mL of hemagglutinin(6μg)at 0,14 and 28 d respectively.The mice were executed in the acute phase(3 d after the last immunization)and the recovery phase(14 d after the last immunization).No abnormal conditions and death were observed in the mice during the experiment period,and their body weight increased.Hematological examination and blood biochemical indexes fluctuated within the normal range,no toxic reaction related to drug administration was found,and no pathological changes were found in organs.CONCLUSION The tetravalent influenza vaccine adjuvanted with PEG6000 and cationic(DOTAP∶DOPC mole ratio 4∶1)-modified liposome has good safety.

关 键 词：脂质体 流感疫苗 安全性 聚乙二醇6000 2 3-二油氧基丙基三-甲基氯化铵 

分 类 号：R392.3[医药卫生—免疫学]