复制缺陷型重组腺病毒rvAdG1VP7免疫学效果的研究

Immune responses induced in vivo by replication defective recombinant adenovirus rvAdG1VP7

目的 对 1株可表达A组轮状病毒主要结构抗原VP7的重组腺病毒rvAdG1VP7的体内免疫学效果进行研究。方法 通过灌胃和滴鼻 2种途径对BALB/c小鼠进行免疫 ,并对免疫后小鼠体液和黏膜免疫进行分析。结果 初次免疫后 ,2组小鼠均有应答 ,但血清IgG抗体滴度及阳转率不同。再次免疫后 ,显示出明显的加强效果。除了血清IgG外 ,小鼠还产生了较强的针对轮状病毒的血清IgA。滴鼻组在肺灌洗液和肠匀浆液中均可检测到SIgA ,灌胃组仅在肠道检测到SIgA。滴鼻组的免疫学效果明显优于灌胃组。对滴鼻组小鼠肺灌洗液IgG/SIgA的阳转率进行了比较 ,发现IgG的应答水平明显高于SIgA。免疫后小鼠血清中IgG的动态观察表明 ,抗体可长期持续至少半年以上。 结论 重组腺病毒载体rvAdG1VP7所取得的良好免疫学效果 ,为我国具有自主知识产权的新型轮状病毒基因工程疫苗的进一步研制奠定了基础。

Objective To study the immune responses induced in vivo by a strain of replication defective recombinant adenovirus rvAdG1VP7 expressing the major neutralizing antigen VP7 of group A rotavirus. Methods BLAB/c mice were used as model immunized intranasally (inl) or orally (ora), respectively, to test the immunization effects of the recombinant adenovirus. Results The systemic immune responses to rotavirus VP7 could be induced in two groups of mice, but the titer and the positive rate of serum IgG antibody were different, and the boost responses were evident after the second inoculation. In addition to IgG, the serum IgA specific to VP7 could also be detected. SIgA was detected in both lung lavage fluid and intestinal homogenate when administered inl to BLAB/c mice, whereas only found in intestinal homogenate in BLAB/c mice administered ora. The results indicated that the immunization efficacy of intranasal inoculation was superior to that of oral inoculation. The level of local IgG was superior to SIgA in lung lavage fluid, suggesting that rotavirus-specific local IgG was likely to be important at mucosal surface after immunization with recombinant replication defective adenovirus. The IgG titer lasted at least 6 months post oral inoculation. Conclusion The ability of rvAdG1VP7 to induce immune responses has laid a solid foundation for the development of rotavirus genetic engineering vaccine against rotavirus infection.