Safety of Tetravalent Influenza Vaccines Adjuvanted with Modified Liposomes
OBJECTIVE To investigate the safety of the tetravalent influenza vaccines adjuvanted with PEG6000 and cationic[2,3-dioleoxy propyltrimethylammonium 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 toxici-ty 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 tox-icity 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 15 μg)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(6 µg)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 examina-tion 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.
万方数据
维普
