Ahmad N, Deeba F, Faisal S M, Khan A, Agrewala J N, Dwivedi V, Owais M
Faculty of Pharmacy, Jamia Hamdard, New Delhi 62, India.
Biochimie. 2006 Oct;88(10):1391-400. doi: 10.1016/j.biochi.2006.04.017. Epub 2006 Jun 2.
Earlier we have demonstrated that novel fusogenic liposomes made up of lipid from Escherichia coli (escheriosomes) have strong tendency to fuse with the plasma membrane of target cells and thereby delivering the entrapped contents into their cytosol. The delivery of entrapped antigen in cytosol of the target cells ensues its processing and presentation along with MHC class I pathway that eventually elicit antigen specific cytotoxic T cells. The result of the present study revealed that immunization of BALB/c mice with escheriosome-encapsulated Salmonella typhimurium (S. typhimurium) cytosolic antigens resulted in the augmentation of antigen specific cytotoxic T cell lymphocyte as well as IgG responses. In contrast, free or conventional liposome (PC liposome) encapsulated antigen failed to induce CD8+ CTLs in the immunized animals. Further, immunization with escheriosome-encapsulated antigen resulted in significant enhancement in the release of IFN-gamma and IgG2a in the experimental animals. Interestingly, the immunization with escheriosome-encapsulated antigen resulted in upregulation of CD80 and CD86 on the surface of antigen presenting cells (APCs) as well. Finally, the results of the present study reveal that immunization of animals with escheriosomes encapsulated antigen protected them against virulent S. typhimurium infection. This was evident by increased survival, and reduced bacterial burden in vital organs of the immunized animals. The data of the present study suggest that escheriosomes can emerge as an effective vehicle for intracellular delivery of antigen and thus hold promise in development of liposome based vaccine against Salmonella and other intracellular pathogens.
此前我们已经证明,由大肠杆菌脂质制成的新型融合脂质体(escheriosomes)具有与靶细胞质膜强烈融合的趋势,从而将包裹的内容物递送至其细胞质溶胶中。将包裹的抗原递送至靶细胞的细胞质溶胶中后,会沿着MHC I类途径进行加工和呈递,最终引发抗原特异性细胞毒性T细胞。本研究结果显示,用包裹鼠伤寒沙门氏菌(S. typhimurium)胞质抗原的escheriosome免疫BALB/c小鼠,可增强抗原特异性细胞毒性T淋巴细胞以及IgG反应。相比之下,游离或常规脂质体(PC脂质体)包裹的抗原未能在免疫动物中诱导CD8+ CTL。此外,用包裹抗原的escheriosome免疫导致实验动物中IFN-γ和IgG2a的释放显著增强。有趣的是,用包裹抗原的escheriosome免疫还导致抗原呈递细胞(APC)表面的CD80和CD86上调。最后,本研究结果表明,用包裹抗原的escheriosome免疫动物可保护它们免受毒力鼠伤寒沙门氏菌感染。这在免疫动物的存活率提高以及重要器官中细菌载量降低方面表现明显。本研究数据表明,escheriosomes可成为一种有效的细胞内抗原递送载体,因此在开发基于脂质体的抗沙门氏菌和其他细胞内病原体疫苗方面具有前景。