Department of Biology, Sciences and Research Branch, Islamic Azad University, Tehran, Iran; Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran.
Acta Trop. 2013 Dec;128(3):528-35. doi: 10.1016/j.actatropica.2013.07.021. Epub 2013 Aug 2.
A suitable adjuvant and delivery system are needed to develop an effective vaccine against leishmaniasis. To induce a Th1 type of response and protection in BALB/c mice against Leishmania major infection, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) nanoliposomes bearing an intrinsic adjuvanticity, were used as an antigen delivery system and immunoadjuvant for soluble Leishmania antigens (SLA). DOTAP liposomes containing different concentrations of SLA were prepared by using lipid film method followed by sonication. The prepared vesicles showed a diameter of about 100nm, a positive zeta potential and approximately 70% encapsulation efficiency of SLA. BALB/c mice were immunized subcutaneously (SC), three times in a 3-week interval with different concentrations of liposomal SLA (12.5, 25, and 50μg of SLA/50μl/mice), free SLA and as well as free liposome. The group of mice received 50μg of SLA in DOTAP-nanoliposomes showed a significantly (p<0.001) smaller footpad swelling and the lowest spleen and footpad parasite burden after the challenge. This group also showed the highest IFN-γ production compared to the other groups, lower IL-4 level and higher IgG2a antibody titer. Taken together, the results indicated that simple DOTAP nanoliposome containing 1μg/μl SLA are appropriate delivery systems to induce a Th1 type of immune response and protection against L. major infection in BALB/c mice.
需要合适的佐剂和递送系统来开发有效的利什曼病疫苗。为了在 BALB/c 小鼠中诱导针对利什曼原虫感染的 Th1 型反应和保护,使用具有内在佐剂活性的 1,2-二油酰基-3-三甲铵丙烷(DOTAP)纳米脂质体作为抗原递送系统和免疫佐剂用于可溶性利什曼抗原(SLA)。通过脂质体薄膜法随后进行超声处理,制备了含有不同浓度 SLA 的 DOTAP 脂质体。制备的囊泡的直径约为 100nm,具有正的 ζ 电位,并且 SLA 的包封效率约为 70%。BALB/c 小鼠通过皮下(SC)免疫,每 3 周间隔 3 次,用不同浓度的脂质体 SLA(12.5、25 和 50μg SLA/50μl/小鼠)、游离 SLA 以及游离脂质体进行免疫。接受 DOTAP 纳米脂质体中 50μg SLA 的小鼠在受到挑战后显示出明显(p<0.001)较小的足垫肿胀和最低的脾脏和足垫寄生虫负担。与其他组相比,该组还显示出最高的 IFN-γ产生,较低的 IL-4 水平和更高的 IgG2a 抗体滴度。总之,这些结果表明,含有 1μg/μl SLA 的简单 DOTAP 纳米脂质体是诱导 BALB/c 小鼠针对 L. major 感染的 Th1 型免疫反应和保护的合适递送系统。