Designing multi-epitope vaccines against Echinococcus granulosus: an in-silico study using immuno-informatics.

IF 2.4 3区 生物学 Q4 CELL BIOLOGY BMC Molecular and Cell Biology Pub Date : 2024-12-30 DOI:10.1186/s12860-024-00524-6
Jadoon Khan, Asma Sadiq, May M Alrashed, Nosheen Basharat, Syed Nadeem Ul Hassan Mohani, Tawaf Ali Shah, Kotb A Attia, Aamer Ali Shah, Hayat Khan, Ijaz Ali, Arif Ahmed Mohammed
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Abstract

Cystic echinococcosis (CE) is a worldwide zoonotic public health issue. The reasons for this include a lack of specific therapy options, increasing antiparasitic drug resistance, a lack of control strategies, and the absence of an approved vaccine. The aim of the current study is to develop a multiepitope vaccine against CE by in-silico identification and using different Antigen B subunits. The five Echinococcus granulosus antigen B (EgAgB) subunits were examined for eminent antigenic epitopes, and then the best B-cell and Major Histocompatibility Complex MHC-binding epitopes were predicted. Most significant epitopes were combined to create an effective multi-epitope vaccine, which was then validated by testing its secondary and tertiary structures, physicochemical properties, and molecular dynamics (MD) modelling. A multi-epitope vaccine construct of 483 amino acid sequences was designed. It contains B-cell, Helper T Lymphocyte (HTL), and Cytotoxic T Lymphocyte (CTL) epitopes as well as the appropriate adjuvant and linker molecules. The resultant vaccinal construct had a GDT-HA value of 0.9725, RMSD of 0.299, MolProbity of 1.891, Clash score of 13.1, Poor rotamers of 0.9, and qualifying features with Rama favoured of 89.9. It was also highly immunogenic and less allergic. The majority of the amino acids were positioned in the Ramachandran plot's favourable area, and during the molecular dynamic simulation at 100 ns, no notable structural abnormalities were noticed. The resultant construct was significantly expressed and received good endorsement in the pIB2-SEC13-mEGFP expressional vector. In conclusion, the current in-silico multi-epitope vaccine may be evaluated in-vitro, in-vivo, and in clinical trials as an immunogenic vaccine model. It can also play a vital role in preventing this zoonotic parasite infection.

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设计针对细粒棘球蚴的多表位疫苗:一项利用免疫信息学的计算机研究。
囊性包虫病(CE)是一个世界性的人畜共患公共卫生问题。造成这种情况的原因包括缺乏特定的治疗选择、抗寄生虫药物耐药性增加、缺乏控制策略以及缺乏批准的疫苗。目前研究的目的是通过计算机识别和使用不同的抗原B亚基来开发一种针对CE的多表位疫苗。通过对5个细粒棘球绦虫抗原B (EgAgB)亚基的检测,预测最佳的B细胞和主要组织相容性复合体mhc结合表位。将大多数重要的表位组合在一起,形成一种有效的多表位疫苗,然后通过测试其二级和三级结构、物理化学性质和分子动力学(MD)模型进行验证。设计了包含483个氨基酸序列的多表位疫苗结构。它含有b细胞、辅助性T淋巴细胞(HTL)和细胞毒性T淋巴细胞(CTL)表位以及相应的佐剂和连接分子。最终构建的疫苗GDT-HA值为0.9725,RMSD为0.299,MolProbity为1.891,Clash评分为13.1,Poor rotamers为0.9,符合Rama偏好的特征为89.9。它还具有高度的免疫原性和较低的过敏性。大多数氨基酸位于Ramachandran图的有利区域,在100 ns的分子动力学模拟中,未发现明显的结构异常。该构建体在pIB2-SEC13-mEGFP表达载体中得到了显著表达,并获得了良好的背书。总之,目前的硅多表位疫苗可以作为免疫原性疫苗模型在体外、体内和临床试验中进行评估。它还可以在预防这种人畜共患寄生虫感染方面发挥重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Molecular and Cell Biology
BMC Molecular and Cell Biology Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
5.50
自引率
0.00%
发文量
46
审稿时长
27 weeks
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