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免疫信息学分析设计针对来自尼日利亚株的拉沙病毒(LASMV)糖蛋白和核蛋白的新型表位疫苗候选物

Immunoinformatics analysis to design novel epitope based vaccine candidate targeting the glycoprotein and nucleoprotein of Lassa mammarenavirus (LASMV) using strains from Nigeria.

机构信息

Department of Bioinformatics & Computational Biology, Centre for BioCode, Benin, Nigeria.

Department of Biochemistry, Faculty of Life Sciences, Ambrose Alli University, Ekpoma, Nigeria.

出版信息

J Biomol Struct Dyn. 2022 Oct;40(16):7283-7302. doi: 10.1080/07391102.2021.1896387. Epub 2021 Mar 15.

DOI:10.1080/07391102.2021.1896387
PMID:33719908
Abstract

Lassa mammarenavirus (LASMV) is responsible for a specific type of acute viral hemorrhagic fever known as Lassa fever. Lack of effective treatments and counter-measures against the virus has resulted in a high mortality rate in its endemic regions. Therefore, in this study, a novel epitope-based vaccine has been designed using the methods of immunoinformatics targeting the glycoprotein and nucleoprotein of the virus. After numerous robust analyses, two CTL epitopes, eight HTL epitopes and seven B-cell epitopes were finally selected for constructing the vaccine. All these most promising epitopes were found to be antigenic, non-allergenic, nontoxic and non-human homolog, which made them suitable for designing the subunit vaccine. Furthermore, the selected T-cell epitopes which were found to be fully conserved across different isolates of the virus, were also considered for final vaccine construction. After that, numerous validation experiments, i.e. molecular docking, molecular dynamics simulation and immune simulation were conducted, which predicted that our designed vaccine should be stable within the biological environment and effective in combating the LASMV infection. In the end, codon adaptation and cloning studies were performed to design a recombinant plasmid for producing the vaccine industrially. However, further and assessments should be done on the constructed vaccine to finally confirm its safety and efficacy.Communicated by Ramaswamy H. Sarma.

摘要

拉萨热病毒(LASMV)是一种特定类型的急性病毒性出血热,称为拉萨热。由于缺乏针对该病毒的有效治疗和对策,其流行地区的死亡率很高。因此,在这项研究中,使用免疫信息学方法针对病毒的糖蛋白和核蛋白设计了一种新型基于表位的疫苗。经过多次严格分析,最终选择了两个 CTL 表位、八个 HTL 表位和七个 B 细胞表位用于构建疫苗。所有这些最有前途的表位都被证明具有抗原性、非变应原性、无毒和非人类同源性,这使它们适合设计亚单位疫苗。此外,还考虑了在不同病毒分离株中完全保守的选定 T 细胞表位用于最终疫苗构建。之后,进行了多次验证实验,即分子对接、分子动力学模拟和免疫模拟,预测我们设计的疫苗在生物环境中应该是稳定的,并能有效抵抗 LASMV 感染。最后,进行了密码子适应和克隆研究,以设计用于工业生产疫苗的重组质粒。然而,还需要对构建的疫苗进行进一步评估,以最终确认其安全性和有效性。通讯作者为 Ramaswamy H. Sarma。

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