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基于计算机的克里米亚-刚果出血热新一代多表位疫苗的配方设计,用作预防性候选药物。

In silico formulation of a next-generation multiepitope vaccine for use as a prophylactic candidate against Crimean-Congo hemorrhagic fever.

机构信息

Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore, 7408, Bangladesh.

Laboratory of Computational Biology, Biological Solution Centre (BioSol Centre), Jashore, 7408, Bangladesh.

出版信息

BMC Med. 2023 Feb 1;21(1):36. doi: 10.1186/s12916-023-02750-9.

Abstract

BACKGROUND

Crimean-Congo hemorrhagic fever (CCHF) is a widespread disease transmitted to humans and livestock animals through the bite of infected ticks or close contact with infected persons' blood, organs, or other bodily fluids. The virus is responsible for severe viral hemorrhagic fever outbreaks, with a case fatality rate of up to 40%. Despite having the highest fatality rate of the virus, a suitable treatment option or vaccination has not been developed yet. Therefore, this study aimed to formulate a multiepitope vaccine against CCHF through computational vaccine design approaches.

METHODS

The glycoprotein, nucleoprotein, and RNA-dependent RNA polymerase of CCHF were utilized to determine immunodominant T- and B-cell epitopes. Subsequently, an integrative computational vaccinology approach was used to formulate a multi-epitopes vaccine candidate against the virus.

RESULTS

After rigorous assessment, a multiepitope vaccine was constructed, which was antigenic, immunogenic, and non-allergenic with desired physicochemical properties. Molecular dynamics (MD) simulations of the vaccine-receptor complex show strong stability of the vaccine candidates to the targeted immune receptor. Additionally, the immune simulation of the vaccine candidates found that the vaccine could trigger real-life-like immune responses upon administration to humans.

CONCLUSIONS

Finally, we concluded that the formulated multiepitope vaccine candidates would provide excellent prophylactic properties against CCHF.

摘要

背景

克里米亚-刚果出血热(CCHF)是一种通过受感染的蜱虫叮咬或与受感染个体的血液、器官或其他体液密切接触而传播给人类和牲畜的广泛疾病。该病毒会导致严重的病毒性出血热爆发,病死率高达 40%。尽管该病毒的病死率最高,但尚未开发出合适的治疗方法或疫苗。因此,本研究旨在通过计算疫苗设计方法来制定针对 CCHF 的多表位疫苗。

方法

利用 CCHF 的糖蛋白、核蛋白和 RNA 依赖性 RNA 聚合酶来确定免疫优势 T 细胞和 B 细胞表位。随后,采用整合计算疫苗学方法来构建针对该病毒的多表位疫苗候选物。

结果

经过严格评估,构建了一种多表位疫苗,该疫苗具有抗原性、免疫原性和非变应原性,且具有理想的理化特性。疫苗-受体复合物的分子动力学(MD)模拟表明,疫苗候选物与靶向免疫受体具有很强的稳定性。此外,对疫苗候选物的免疫模拟发现,疫苗接种后可在人体内引发类似真实免疫反应。

结论

最后,我们得出结论,所制定的多表位疫苗候选物将为预防 CCHF 提供出色的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbfd/9893611/439bdb3e6342/12916_2023_2750_Fig1_HTML.jpg

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