Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Exp Parasitol. 2012 Dec;132(4):403-9. doi: 10.1016/j.exppara.2012.09.001. Epub 2012 Sep 13.
To develop an efficient liposomal vaccine delivery system, the size of liposomes is critical to their adjuvant activities. In the present study, liposomes with different sizes (100, 400, 1000 nm) containing recombinant major surface glycoprotein of Leishmania (rgp63) were prepared, characterized, and inoculated subcutaneously into BALB/c mice to evaluate the rate of protection and the type of immune response generated against leishmaniasis. The lowest footpad lesion size and splenic parasite burden were seen in the mice immunized with large size (≥400 nm) liposomes after challenge with Leishmania major. The production of IFN-γ was only elevated in the spleen cells of mice immunized with large size (≥400 nm) liposomes. The highest IgG2a/IgG1 ratio was also seen in the sera of the mice immunized with large size (≥400 nm) liposomes before and 14 weeks after challenge. The results showed that immunization with small size (100 nm) liposomes induces a Th2 response, whereas immunization with large size (≥400 nm) liposomes induces a Th1 type of immune response. There was no significant difference in the type of induced immune response between the mice immunized with liposomes of 400 nm and those immunized with liposomes of 1000 nm or unextruded. The results of the current study demonstrated that the size of liposomes plays a significant role in the type of generated immune response.
为了开发高效的脂质体疫苗递送系统,脂质体的大小对于其佐剂活性至关重要。在本研究中,制备了含有重组利什曼原虫主要表面糖蛋白(rgp63)的不同大小(100、400、1000nm)的脂质体,对其进行了表征,并皮下接种于 BALB/c 小鼠,以评估对利什曼病的保护率和产生的免疫应答类型。在受到大(≥400nm)脂质体免疫的小鼠中,最小的足底病变和脾脏寄生虫负荷可见于大(≥400nm)脂质体免疫的小鼠。仅在大(≥400nm)脂质体免疫的小鼠的脾细胞中升高 IFN-γ的产生。在受到大(≥400nm)脂质体免疫的小鼠的血清中,IgG2a/IgG1 比值也最高。结果表明,小(100nm)脂质体免疫诱导 Th2 反应,而大(≥400nm)脂质体免疫诱导 Th1 型免疫应答。在受到 400nm 脂质体免疫的小鼠与受到 1000nm 脂质体免疫或未挤出脂质体免疫的小鼠之间,诱导的免疫应答类型没有显著差异。本研究结果表明,脂质体的大小在产生的免疫应答类型中起重要作用。