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G糖蛋白中两个高度相似的LAEDDTNAQKT和LTDKIGTEI表位可能有助于基于表位的有效疫苗设计,以对抗致病性亨尼帕病毒。

Two highly similar LAEDDTNAQKT and LTDKIGTEI epitopes in G glycoprotein may be useful for effective epitope based vaccine design against pathogenic Henipavirus.

作者信息

Parvege Md Masud, Rahman Monzilur, Nibir Yead Morshed, Hossain Mohammad Shahnoor

机构信息

Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka 1000, Bangladesh.

Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka 1000, Bangladesh.

出版信息

Comput Biol Chem. 2016 Apr;61:270-80. doi: 10.1016/j.compbiolchem.2016.03.001. Epub 2016 Mar 3.

Abstract

Nipah virus and Hendra virus, two members of the genus Henipavirus, are newly emerging zoonotic pathogens which cause acute respiratory illness and severe encephalitis in human. Lack of the effective antiviral therapy endorses the urgency for the development of vaccine against these deadly viruses. In this study, we employed various computational approaches to identify epitopes which has the potential for vaccine development. By analyzing the immune parameters of the conserved sequences of G glycoprotein using various databases and bioinformatics tools, we identified two potential epitopes which may be used as peptide vaccines. Using different B cell epitope prediction servers, four highly similar B cell epitopes were identified. Immunoinformatics analyses revealed that LAEDDTNAQKT is a highly flexible and accessible B-cell epitope to antibody. Highly similar putative CTL epitopes were analyzed for their binding with the HLA-C 12*03 molecule. Docking simulation assay revealed that LTDKIGTEI has significantly lower binding energy, which bolstered its potential as epitope-based vaccine design. Finally, cytotoxicity analysis has also justified their potential as promising epitope-based vaccine candidate. In sum, our computational analysis indicates that either LAEDDTNAQKT or LTDKIGTEI epitope holds a promise for the development of universal vaccine against all kinds of pathogenic Henipavirus. Further in vivo and in vitro studies are necessary to validate the obtained findings.

摘要

尼帕病毒和亨德拉病毒是亨尼帕病毒属的两个成员,是新出现的人畜共患病病原体,可导致人类急性呼吸道疾病和严重脑炎。缺乏有效的抗病毒治疗方法凸显了开发针对这些致命病毒的疫苗的紧迫性。在本研究中,我们采用了各种计算方法来鉴定具有疫苗开发潜力的表位。通过使用各种数据库和生物信息学工具分析G糖蛋白保守序列的免疫参数,我们鉴定出两个可能用作肽疫苗的潜在表位。使用不同的B细胞表位预测服务器,鉴定出四个高度相似的B细胞表位。免疫信息学分析表明,LAEDDTNAQKT是一种对抗体具有高度灵活性和可及性的B细胞表位。对高度相似的推定细胞毒性T淋巴细胞(CTL)表位与HLA - C 12*03分子的结合情况进行了分析。对接模拟分析表明,LTDKIGTEI具有显著更低的结合能,这支持了其作为基于表位的疫苗设计的潜力。最后,细胞毒性分析也证明了它们作为有前景的基于表位的疫苗候选物的潜力。总之,我们的计算分析表明,LAEDDTNAQKT或LTDKIGTEI表位有望用于开发针对各种致病性亨尼帕病毒的通用疫苗。需要进一步的体内和体外研究来验证所获得的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d1/7172312/a21e6d6f2dd1/fx1.jpg

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