人轮状病毒抗原非复制型重组腺病毒黏膜免疫效果的研究

Mucosal immune response induced by recombinant adenoviruses expressing human rotavirus genes

目的 :对人轮状病毒抗原非复制型重组腺病毒诱导黏膜免疫的效果进行初步评价。方法 :用表达轮状病毒VP7、VP6基因的 3株重组腺病毒rvAdG1VP7(G)、rvAdG1VP7和rvAdVP6 ,分别通过灌胃和滴鼻两种途径对BALB C小鼠进行 2次免疫后 ,对肺灌洗液和肺、肠粘膜组织匀浆液中轮状病毒特异性的分泌型IgA(secretoryIgA ,SIgA)和local IgG进行检测。结果 :对肺灌洗液中特异性SIgA进行检测 ,发现滴鼻组的免疫学效果明显优于灌胃组。对肺、肠组织匀浆液中特异性IgA的分析表明 ,灌胃途径刺激异位粘膜组织产生免疫应答的能力较弱。对rvAdVP6滴鼻组小鼠肺灌洗液 (1∶2 0 )特异性local IgG和SI gA的阳转率进行比较 ,发现特异性local IgG的应答水平明显高于特异性SIgA。结论 :重组腺病毒可有效诱导针对轮状病毒的黏膜免疫。此研究为轮状病毒基因工程疫苗的免疫方案、免疫途径及免疫保护作用等的进一步研究奠定了基础。

Objective:To evaluate the mucosal immune effects in vivo induced by recombinant adenovirus expressing main constructive antigens of human rotavirus(RV).Methods:BLAB/c mice were administered three different recombinant adenoviruses rvAdG1VP7(G),rvAdG1VP7 and rvAdVP6 which expresses VP7 or VP6 separately via intranasal and oral routes,respectively.Both RV specific secretory IgA(SIgA) and RV specific local IgG in lung lavage fluid,lung and intestine homogenate fluid were investigated after 2 round immunizations.Results:The titer of the specific SIgA in the lung lavage fluid of mice immunized intranasally with different recombinant adenoviruses were all superior to that of mice immunized orally.The specific IgA in the lung and intestine homogenate fluids could be induced after intranasal immunization,and in the same time,the specific IgA only be found in the intestine after oral immunization.In contrast to the positive rate of the specific local IgG in lung lavage fluid with the specific SIgA after intranasal immunization using rvAdVP6,found that the level of the specific local IgG was superior to that of the specific SIgA.Conclusion:The recombinant adenoviruses could prime mucosal immunity specific to RV effecxtively.The study laid a solid foundation for the further study of the vaccine formulation,inoculation route and protective immunity,etc. [