Parasitology Department, Medical Sciences Faculty, Tarbiat Modares University, Tehran, Iran.
Arch Razi Inst. 2022 Dec 31;77(6):2223-2233. doi: 10.22092/ARI.2022.358499.2238. eCollection 2022 Dec.
Leishmaniasis is one of the major health problems in most countries of the world. Millions of people around the world are at risk for the disease. Given the prevalence of this parasite in Iran and developing countries and the emergence of resistance in some cases to existing drugs, developing an effective vaccine against leishmaniasis is necessary. This research aims to design a multi-epitope vaccine derived from LACK, LeIF, GP63, and SMT antigens of based on the combination of bioinformatics methods. The synthesized construct with 16.86 KDa was cloned and sub-cloned in pEGFP- N1 and pLEXSY-neo2, respectively. They were then transfected in promastigotes of . After confirmation of expression, immunization was carried out in 8 groups of BALB/c mice (9 mice per group) three times at two-week intervals. Cellular immune responses were assessed before and after the challenge by . Furthermore, at 3rd week post-infection, the survival rate, mean lesion size, and parasite burden were assessed. All vaccinated mice demonstrated partial immunity to higher IFN-γ levels than the control groups (<0.05). Immunized mice with cytosolic complex (G1) indicated the highest levels of IFN-ɤ and ratio of IFN ɤ/ IL-4, the lowest levels of IL-4 and IL-10 compared to control and the other groups (≤0.05), and produced a partial Th1 immune response. Mean lesion size and parasite burden of G1 and G5 reduced significantly compared to the other and control groups post-challenge (<0.05). The outputs of our result could be a hopeful sign in the achievement of practical approaches as multi-epitope vaccines against .
利什曼病是世界上大多数国家的主要卫生问题之一。全球数百万人面临这种疾病的风险。鉴于这种寄生虫在伊朗和发展中国家的流行,以及某些情况下对现有药物的耐药性的出现,开发针对利什曼病的有效疫苗是必要的。本研究旨在基于生物信息学方法的组合,从 LACK、LeIF、GP63 和 SMT 抗原设计多表位疫苗。合成的构建体为 16.86 kDa,分别在 pEGFP-N1 和 pLEXSY-neo2 中进行克隆和亚克隆。然后将它们转染到 的前鞭毛体中。在确认表达后,在 8 组 BALB/c 小鼠(每组 9 只)中进行了 3 次免疫接种,间隔两周。在挑战前后通过 评估细胞免疫反应。此外,在感染后第 3 周评估存活率、平均病变大小和寄生虫负担。与对照组相比,所有接种疫苗的小鼠均表现出对更高 IFN-γ水平的部分免疫(<0.05)。与对照组和其他组相比,与细胞溶质复合物(G1)免疫的小鼠表现出最高水平的 IFN-ɤ和 IFN-ɤ/IL-4 比值,最低水平的 IL-4 和 IL-10(≤0.05),并产生部分 Th1 免疫反应。与其他组和对照组相比,G1 和 G5 的平均病变大小和寄生虫负担在挑战后显著降低(<0.05)。我们的结果可能是朝着实现多表位疫苗等实用方法迈出的有希望的一步。