流感疫苗脂质体干粉黏膜免疫研究

Study on mucosal immunity of influenza vaccine lyophilized liposome

目的考察H3N2单价流感疫苗脂质体诱发呼吸道黏膜免疫的效果,并比较呼吸道不同部位产生抗体水平的差异。方法将实验小鼠分为非脂质体疫苗原液组、脂质体疫苗冻干粉组、阳性对照和阴性对照组(n=5)。非脂质体疫苗原液组和脂质体疫苗冻干粉组各以每只4μg和6μg血凝素含量(H3N2亚型)滴鼻免疫,同时以非脂质体疫苗原液腹腔给药和脂质体疫苗冻干粉腹腔给药作为阳性对照,以未免疫小鼠(磷酸盐缓冲液给药)作为阴性对照。免疫28 d后,采用间接ELISA法检测血清IgG和呼吸道黏膜sIgA分泌水平。结果脂质体滴鼻给药诱导的黏膜sIgA水平高于腹腔给药免疫组(P<0.05),上呼吸道(鼻咽部)黏膜sIgA水平明显高于下呼吸道(肺部)(P<0.01);与非脂质体组滴鼻免疫相比,上呼吸道脂质体组诱发的sIgA水平较低(P<0.01),而下呼吸道脂质体组诱发的sIgA水平较高(P<0.05)。结论流感疫苗脂质体滴鼻给药能有效诱发体液免疫和呼吸道黏膜免疫,上呼吸道黏膜免疫水平高于下呼吸道,但与非脂质体相比,脂质体在下呼吸道(肺部)能表现出更好的免疫佐剂效应。

Objective To evaluate the mucosal immunity effects of H3N2 influenza vaccine lyophilized liposomes,and to compare the antibody levels in different parts of the respiratory tract.Method Experimental mice were divided into the influenza vaccine non-liposome group,the influenza vaccine lyophilized liposome group,positive control group and negative control group（n=5）.4μg and 6μg hemagglutinin（H3N2 subtype） per mouse were delivered intranasally to the influenza vaccine non-liposome group and the influenza vaccine lyophilized liposome group mice,with intraperitoneally injected influenza vaccine non-liposome group and lyophilized liposome group mice as the positive control,and PBS intraperotoneal injection group as the negative control.The indirect ELISA method was used to measure the serum IgG and respiratory mucosal sIgA levels after 28 days of immunization.Result The respiratory sIgA level of the influenza vaccine lyophilized liposome group was higher than that of the influenza vaccine non-liposome group（P〈0.05）.The sIgA level of upper respiratory tract（nasopharynx） was significantly higher than that of the lower respiratory tract（lung）（P〈0.01）.Conclusion The influenza vaccine lyophilized liposome could effectively induce humoral immunity and mucosal immunity of respiratory.The mucosal immunity effect of upper respiratory tract was higher than that of lower respiratory tract.But comparing with non-liposome vaccine,liposome performs well on lower respiratory tract in terms of adjuvant effect.