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针对盘尾丝虫病和相关丝虫病的多表位疫苗候选物的计算机设计。

In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases.

机构信息

Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM, Université Libre de Bruxelles, Gosselies, Belgium.

Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon.

出版信息

Sci Rep. 2019 Mar 13;9(1):4409. doi: 10.1038/s41598-019-40833-x.

DOI:10.1038/s41598-019-40833-x
PMID:30867498
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6416346/
Abstract

Onchocerciasis is a parasitic disease with high socio-economic burden particularly in sub-Saharan Africa. The elimination plan for this disease has faced numerous challenges. A multi-epitope prophylactic/therapeutic vaccine targeting the infective L3 and microfilaria stages of the parasite's life cycle would be invaluable to achieve the current elimination goal. There are several observations that make the possibility of developing a vaccine against this disease likely. For example, despite being exposed to high transmission rates of infection, 1 to 5% of people have no clinical manifestations of the disease and are thus considered as putatively immune individuals. An immuno-informatics approach was applied to design a filarial multi-epitope subunit vaccine peptide consisting of linear B-cell and T-cell epitopes of proteins reported to be potential novel vaccine candidates. Conservation of the selected proteins and predicted epitopes in other parasitic nematode species suggests that the generated chimera could be helpful for cross-protection. The 3D structure was predicted, refined, and validated using bioinformatics tools. Protein-protein docking of the chimeric vaccine peptide with the TLR4 protein predicted efficient binding. Immune simulation predicted significantly high levels of IgG, T-helper, T-cytotoxic cells, INF-γ, and IL-2. Overall, the constructed recombinant putative peptide demonstrated antigenicity superior to current vaccine candidates.

摘要

盘尾丝虫病是一种具有高社会经济负担的寄生虫病,尤其在撒哈拉以南非洲地区。该疾病的消除计划面临诸多挑战。针对寄生虫生活史的感染性 L3 和微丝蚴阶段的多表位预防性/治疗性疫苗对于实现当前的消除目标将是非常宝贵的。有一些观察结果使得开发针对这种疾病的疫苗成为可能。例如,尽管暴露于高感染传播率下,但仍有 1%至 5%的人没有疾病的临床症状,因此被认为是假定的免疫个体。应用免疫信息学方法来设计一种丝虫多表位亚单位疫苗肽,该疫苗肽由据报道为潜在新型疫苗候选物的蛋白质的线性 B 细胞和 T 细胞表位组成。选择的蛋白质和预测的表位在其他寄生线虫物种中的保守性表明,产生的嵌合体可能有助于交叉保护。使用生物信息学工具预测、精修和验证了 3D 结构。预测了嵌合疫苗肽与 TLR4 蛋白的蛋白-蛋白对接具有有效的结合。免疫模拟预测 IgG、辅助性 T 细胞、细胞毒性 T 细胞、INF-γ 和 IL-2 的水平显著升高。总体而言,构建的重组假定肽表现出比现有疫苗候选物更好的抗原性。

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