Mesh : Nipah Virus / immunology Viral Vaccines / immunology Glycoproteins / immunology chemistry Humans Henipavirus Infections / prevention & control immunology Computer Simulation Epitopes / immunology chemistry Molecular Dynamics Simulation Nucleocapsid / immunology Molecular Docking Simulation

来  源:   DOI:10.1371/journal.pone.0300507   PDF(Pubmed)

Abstract:
According to the 2018 WHO R&D Blueprint, Nipah virus (NiV) is a priority disease, and the development of a vaccine against NiV is strongly encouraged. According to criteria used to categorize zoonotic diseases, NiV is a stage III disease that can spread to people and cause unpredictable outbreaks. Since 2001, the NiV virus has caused annual outbreaks in Bangladesh, while in India it has caused occasional outbreaks. According to estimates, the mortality rate for infected individuals ranges from 70 to 91%. Using immunoinformatic approaches to anticipate the epitopes of the MHC-I, MHC-II, and B-cells, they were predicted using the NiV glycoprotein and nucleocapsid protein. The selected epitopes were used to develop a multi-epitope vaccine construct connected with linkers and adjuvants in order to improve immune responses to the vaccine construct. The 3D structure of the engineered vaccine was anticipated, optimized, and confirmed using a variety of computer simulation techniques so that its stability could be assessed. According to the immunological simulation tests, it was found that the vaccination elicits a targeted immune response against the NiV. Docking with TLR-3, 7, and 8 revealed that vaccine candidates had high binding affinities and low binding energies. Finally, molecular dynamic analysis confirms the stability of the new vaccine. Codon optimization and in silico cloning showed that the proposed vaccine was expressed to a high degree in Escherichia coli. The study will help in identifying a potential epitope for a vaccine candidate against NiV. The developed multi-epitope vaccine construct has a lot of potential, but they still need to be verified by in vitro & in vivo studies.
摘要:
根据2018年世卫组织研发蓝图,尼帕病毒(NiV)是一种重点疾病,强烈鼓励开发针对NiV的疫苗。根据人畜共患疾病分类的标准,NiV是一种III期疾病,可以传播给人们并引起不可预测的爆发。自2001年以来,NiV病毒每年在孟加拉国爆发,而在印度,它偶尔会引起疫情。根据估计,感染者的死亡率从70%到91%不等.使用免疫信息学方法来预测MHC-I的表位,MHC-II,B细胞,它们是使用NiV糖蛋白和核衣壳蛋白预测的。所选择的表位用于开发与接头和佐剂连接的多表位疫苗构建体,以改善对疫苗构建体的免疫应答。工程疫苗的3D结构是预期的,优化,并使用各种计算机模拟技术进行确认,以便可以评估其稳定性。根据免疫学模拟试验,发现疫苗接种引发针对NiV的靶向免疫应答。与TLR-3、7和8对接显示候选疫苗具有高结合亲和力和低结合能。最后,分子动力学分析证实了新疫苗的稳定性。密码子优化和计算机克隆表明,该疫苗在大肠杆菌中高度表达。该研究将有助于确定针对NiV的疫苗候选物的潜在表位。开发的多表位疫苗构建体具有很大的潜力,但它们仍然需要通过体外和体内研究来验证。
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