In-silico development of multi-epitope subunit vaccine against lymphatic filariasis.

IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-20 DOI:10.1080/07391102.2023.2294838
Pratik Singh, Samir Shaikh, Sakshi Gupta, Reeshu Gupta
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Abstract

The World Health Organization in 2022 reported that more than 863 million people in 50 countries are at risk of developing lymphatic filariasis (LF), a disease caused by parasitic infection. Immune responses to parasites suggest that the development of a prophylactic vaccine against LF is possible. Using a reverse vaccinology approach, the current study identified Trehalose-6-phosphatase (TPP) as a potential vaccine candidate among 15 reported vaccine antigens for B. malayi. High-ranking B and T-cell epitopes in the Trehalose-6-phosphatase (TPP) were shortlisted using online servers for subsequent analysis. We selected these peptides to construct a vaccine model using I-TASSER and GalaxyRefine server. The vaccine construct showed favorable physicochemical properties, high antigenicity, no allergenicity, no toxicity, and high stability. Structural validation using the Ramachandran plot showed that 98% of the residues were in favorable or mostly allowed regions. Molecular docking and simulation showed a strong binding affinity and stability of the subunit vaccine with toll-like receptor 4 (TLR4). Furthermore, the subunit vaccine showed a strong IgG/IgM response, with the disappearance of the antigen. We propose that our vaccine construct should be further evaluated using cellular and animal models to develop a vaccine that is safe and effective against LF.

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针对淋巴丝虫病的多表位亚单位疫苗的分子内开发。
世界卫生组织 2022 年报告称,50 个国家的超过 8.63 亿人有可能患上由寄生虫感染引起的淋巴丝虫病(LF)。对寄生虫的免疫反应表明,开发预防淋巴丝虫病的疫苗是可能的。本研究采用反向疫苗学方法,从已报道的 15 种马拉伊丝虫疫苗抗原中确定了特雷弗糖-6-磷酸酶(TPP)作为潜在的候选疫苗。我们利用在线服务器筛选出了特雷哈尔糖-6-磷酸酶(TPP)中的高等级 B 细胞和 T 细胞表位,并进行了后续分析。我们利用 I-TASSER 和 GalaxyRefine 服务器选择了这些肽来构建疫苗模型。该疫苗构建体显示出良好的理化特性、高抗原性、无过敏性、无毒性和高稳定性。使用拉马钱德兰图进行的结构验证表明,98% 的残基位于有利或主要允许区域。分子对接和模拟显示亚单位疫苗与收费样受体 4(TLR4)有很强的结合亲和力和稳定性。此外,亚单位疫苗显示出强烈的 IgG/IgM 反应,抗原消失。我们建议使用细胞和动物模型对我们的疫苗构建物进行进一步评估,以开发出安全有效的抗肺结核疫苗。
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来源期刊
Journal of Biomolecular Structure & Dynamics
Journal of Biomolecular Structure & Dynamics 生物-生化与分子生物学
CiteScore
8.90
自引率
9.10%
发文量
597
审稿时长
2 months
期刊介绍: The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.
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In silico identification and characterization of small molecule binding to the CD1d immunoreceptor. In silico screening of natural products as uPAR inhibitors via multiple structure-based docking and molecular dynamics simulations. In-silico development of multi-epitope subunit vaccine against lymphatic filariasis. 3D-QSAR and ADMET studies of morpholino-pyrimidine inhibitors of DprE1 from Mycobacterium tuberculosis. An effective Alzheimer's disease segmentation and classification using Deep ResUnet and Efficientnet.
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