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载有可溶性莱什曼抗原(SLA)的纳米脂质体在 BALB/c 小鼠中的免疫作用及 MPL 和咪喹莫特佐剂对其增强作用

The role of MPL and imiquimod adjuvants in enhancement of immune response and protection in BALB/c mice immunized with soluble Leishmania antigen (SLA) encapsulated in nanoliposome.

机构信息

a Department of Medical Nanotechnology, School of Advanced Technologies in Medicine , Tehran University of Medical Sciences , Tehran , Iran.

b Department of Proteomics and Biochemistry , Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization(AREEO) , Karaj , Iran.

出版信息

Artif Cells Nanomed Biotechnol. 2018;46(sup2):324-333. doi: 10.1080/21691401.2018.1457042. Epub 2018 Apr 1.

Abstract

Adjuvants play an essential role in the induction of immunity against leishmaniasis. In this study, monophosphoryl lipid A (MPL) and imiquimod (IMQ) were used as TLR ligands adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Nanoliposomes containing soluble Leishmania antigens (SLA) and adjuvants were consisted of DSPC, DSPG and Chol prepared by using lipid film method followed by bath sonication. The size of nanoliposomes was around 95 nm and their zeta potential was negative. BALB/c mice were immunized by liposomal formulations of lip/SLA, lip/MPL/SLA, lip/IMQ/SLA, lip/MPL/IMQ/SLA, lip/SLA + lip/IMQ, lip/SLA + lip/MPL, lip/SLA + lip/MPL/IMQ and five controls of SLA, lip/MPL, lip/IMQ, lip/MPL/IMQ and buffer by subcutaneously (SC) injections, three times in 2 weeks intervals. The synergic effect of two adjuvants when they are used in one formulation showed significantly (p < .001) smaller footpad swelling and the lowest parasite burden in lymph node and foot after the challenge. IgG2a in these groups showed the higher titre compared to control groups, which is compatible with the high IFN-γ production and lowest IL-4. Taken together the results indicated that co-delivery of MPL and IMQ adjuvants and antigen in nanoliposome carrier could be an appropriate delivery system to induce cellular immunity pathway against leishmaniasis.

摘要

佐剂在诱导抗利什曼病免疫中起着至关重要的作用。在这项研究中,单磷酰脂质 A(MPL)和咪喹莫特(IMQ)被用作 TLR 配体佐剂,以增强针对利什曼病的免疫原性和保护率。含有可溶性利什曼抗原(SLA)和佐剂的纳米脂质体由 DSPC、DSPG 和 Chol 通过脂质体薄膜法制备,然后进行浴超声处理。纳米脂质体的大小约为 95nm,其 zeta 电位为负。BALB/c 小鼠通过皮下(SC)注射五种对照制剂 SLA、lip/MPL、lip/IMQ、lip/MPL/IMQ 和缓冲液,以及 lip/SLA、lip/MPL/SLA、lip/IMQ/SLA、lip/MPL/IMQ/SLA、lip/SLA+lip/IMQ 和 lip/SLA+lip/MPL 两种制剂的脂质体制剂进行免疫,每两周注射 3 次。当两种佐剂在一种制剂中使用时,协同作用表现出明显(p < 0.001)较小的足垫肿胀和淋巴结和足部寄生虫负荷最低。这些组中的 IgG2a 与对照组相比显示出更高的滴度,这与高 IFN-γ 产生和最低的 IL-4 一致。总之,结果表明,MPL 和 IMQ 佐剂和抗原在纳米脂质体载体中的共递送可以成为诱导针对利什曼病的细胞免疫途径的合适递送系统。

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