海藻酸钠水凝胶包装以提升腺病毒载体流感疫苗免疫保护效率的机制研究

Recombinant adenoviruses (Ad) have shown great promise as a vaccine platform for their ability to stimulate potent cellular and humoral responses against harbored antigens. Somehow this application was hampered due to anti-Ad immunity elicited by the initial immunization which usually prevents productive infection with subsequent immunization. Our pre-work showed that encapsulation of Ad-vectored vaccines with alginate gel could significantly protect them from degrading and maintaining their biological activity in vitro. In this study we want to determine whether Ad-vectored vaccines encapsulated in alginate gel would circumvent the pre-existing anti-Ad specific immune response and maintain the immunology efficiency in vivo. Also we would analyze the immunological effects initiated by alginate gel encapsulation in detail, demonstrate the changing in cellular and humoral responses. We hope this study would provide a reasonable strategy to expand the application of Ad-vectored vaccines.

我们及其他研究人员先前的研究显示以腺病毒（Ad5）为载体的如HIV、流感、结核等疫苗可诱导较强的免疫反应。但在实际应用中由于大部分人群体内已存在抗腺病毒中和抗体，或经一次使用腺病毒载体疫苗后即会产生高滴度的中和抗体，从而限制了腺病毒载体疫苗的使用及效果。我们拟通过海藻酸钠水凝胶对腺病毒载体疫苗进行包装，以克服抗体的中和作用并提高腺病毒载体的抗原传递能力。前期实验结果表明，水凝胶包装的腺病毒粒子存活时间明显延长。我们拟在小鼠流感模型中探索水凝胶包装腺病毒载体的免疫学效应，对体液和细胞免疫趋向的影响，尤其是验证水凝胶包装腺病毒载体疫苗能否抵御抗体对腺病毒的中和作用，以及是否具有缓释作用，以延长免疫刺激的时间。从而为提升和优化腺病毒作为疫苗载体的实用性提供新的思路。