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一种针对多表位融合的新型免疫原性结构:计算机模拟研究

A New Immunogenic Structure of Polyepitopic Fusion against : In Silico Study.

作者信息

Pirmoradi Saeed, Khadem Mohammad Darvish, Monjezi Zohre, Bahrami Somayeh, Nzelu Chukwunonso O

机构信息

Department of Basic Sciences, Division of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

Department of Animal Science, Faculty of Animal Science and Food Technology, Agricultural Sciences and Natural Resources University of Khuzestan, Mollasani, Iran.

出版信息

Iran J Parasitol. 2024 Jul-Sep;19(3):290-304. doi: 10.18502/ijpa.v19i3.16387.

Abstract

BACKGROUND

The lack of complete protection against leishmaniasis and the challenges of anti-leishmaniasis drug treatment have made the treatment process more difficult. This study aimed to develop a new strategy for preparing a vaccine against cutaneous leishmaniasis using some of the antigenic proteins of the parasite.

METHODS

This study was carried out in 2022 at Shahid Chamran University of Ahvaz, Ahvaz, Iran. After preparing suitable epitopes of the parasite and examining their antiparasitic properties, the process of making a fusion vaccine was performed and with the help of various bioinformatics tools, physicochemical and structural properties as well as immunological and simulation properties were studied and finally optimized. Construction and cloning were performed in the K12 system and finally, the docking process was performed with Toll-like receptors (TLRs), major histocompatibility complex I (MHC-I), and MHC-II receptors. With the help of selected epitopes of the parasite, which had a high percentage of population coverage, a stable, antigenic, and non-allergenic chimeric vaccine was predicted.

RESULTS

The results of the structural analysis of the TLR5\vaccine complex and simulation of its molecular dynamics showed a sufficiently stable binding. It also showed good potential for stimulation and production of active B cells and memory, as well as the potential for CD8+ T, CD4+ T cell production and development of Th2 and Th1-induced immune responses.

CONCLUSION

Computational results showed that the designed immunogenic structure has the potential to adequately stimulate cellular and humoral immune responses against parasitic disease. As a result of evaluating the effectiveness of the candidate vaccine through in vivo and in vitro immunological tests, it can be suggested as a vaccine against .

摘要

背景

对利什曼病缺乏完全防护以及抗利什曼病药物治疗面临的挑战使得治疗过程更加困难。本研究旨在利用该寄生虫的一些抗原蛋白开发一种制备皮肤利什曼病疫苗的新策略。

方法

本研究于2022年在伊朗阿瓦士的沙希德·查姆兰大学开展。在制备该寄生虫合适的表位并检测其抗寄生虫特性后,进行了融合疫苗的制备过程,并借助各种生物信息学工具研究了物理化学和结构特性以及免疫学和模拟特性,最终进行了优化。在K12系统中进行构建和克隆,最后与Toll样受体(TLRs)、主要组织相容性复合体I(MHC-I)和MHC-II受体进行对接过程。借助该寄生虫具有高人群覆盖率的选定表位,预测了一种稳定、抗原性且无致敏性的嵌合疫苗。

结果

TLR5/疫苗复合物的结构分析及其分子动力学模拟结果显示出足够稳定的结合。它还显示出刺激和产生活性B细胞及记忆细胞的良好潜力,以及产生CD8 + T、CD4 + T细胞和诱导Th2及Th1免疫反应的潜力。

结论

计算结果表明,设计的免疫原性结构有潜力充分刺激针对该寄生虫病的细胞免疫和体液免疫反应。通过体内和体外免疫学试验评估候选疫苗的有效性后,可建议将其作为针对该寄生虫的疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8237/11417980/fd1ee12c08aa/IJPA-19-290-g001.jpg

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