Dehghani Amir, Mamizadeh Mina, Karimi Atena, Hosseini Seyyed Amir, Siamian Davood, Shams Morteza, Ghiabi Shadan, Basati Gholam, Abaszadeh Amir
Department of Nursery, Neyshabur University of Medical Sciences, Neyshabur, Iran.
Department of Dermatology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran; Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran.
J Genet Eng Biotechnol. 2024 Mar;22(1):100355. doi: 10.1016/j.jgeb.2024.100355. Epub 2024 Feb 2.
There is no currently approved human vaccine against leishmaniasis. Utilization of immunogenic antigens and their epitopes capable of enhancing immune responses against leishmaniasis is a crucial step for rational in silico vaccine design. The objective of this study was to generate and evaluate a potential vaccine candidate against leishmaniasis, designed by immunodominant proteins from gp46 and gp63 of Leishmania major, which can stimulate helper T-lymphocytes (HTL) and cytotoxic T-lymphocytes (CTL). For this aim, the IFN-γ-inducing MHC-I and MHC-II binders were predicted for each examined protein (gp46 and gp63) and connected with appropriate linkers, along with an adjuvant (Mycobacterium tuberculosis L7/L12) and a histidine tag. The vaccine's stability, antigenicity, structure, and interaction with the TLR-4 receptor were evaluated in silico. The resulting chimeric vaccine was composed of 344 amino acids and had a molecular weight of 35.64 kDa. Physico-chemical properties indicated that it was thermotolerant, soluble, highly antigenic, and non-allergenic. Predictions of the secondary and tertiary structures were made, and further analyses confirmed that the vaccine construct could interact with the human TLR-4 receptor. Virtual immune simulation demonstrated strong stimulation of T-cell responses, particularly by an increase in IFN-γ, following vaccination. In summary, the in silico data indicated that the vaccine candidate showed high antigenicity in humans. It was also found to trigger significant levels of clearance mechanisms and other components of the cellular immune profile. Nevertheless, further wet experiments are required to properly assess the efficacy of this multi-epitope vaccine candidate against leishmaniasis.
目前尚无获批的针对利什曼病的人用疫苗。利用能够增强针对利什曼病免疫反应的免疫原性抗原及其表位，是合理进行计算机辅助疫苗设计的关键步骤。本研究的目的是构建并评估一种针对利什曼病的潜在候选疫苗，该疫苗由来自硕大利什曼原虫gp46和gp63的免疫显性蛋白设计而成，能够刺激辅助性T淋巴细胞（HTL）和细胞毒性T淋巴细胞（CTL）。为此，针对每种检测蛋白（gp46和gp63）预测了诱导IFN-γ的MHC-I和MHC-II结合物，并与合适的接头相连，同时连接一种佐剂（结核分枝杆菌L7/L12）和一个组氨酸标签。在计算机上评估了该疫苗的稳定性、抗原性、结构以及与TLR-4受体的相互作用。所得嵌合疫苗由344个氨基酸组成，分子量为35.64 kDa。物理化学性质表明它耐热、可溶、高度抗原性且无致敏性。对二级和三级结构进行了预测，进一步分析证实该疫苗构建体可与人TLR-4受体相互作用。虚拟免疫模拟显示接种疫苗后T细胞反应受到强烈刺激，尤其是IFN-γ水平升高。总之，计算机分析数据表明该候选疫苗在人体中具有高抗原性。还发现它能触发显著水平的清除机制和细胞免疫谱的其他成分。然而，需要进一步的湿实验来正确评估这种多表位候选疫苗对利什曼病的疗效。
