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Exploiting the Reverse Vaccinology Approach to Design Novel Subunit Vaccine against Ebola Virus
medRxiv - Allergy and Immunology Pub Date : 2020-01-03 , DOI: 10.1101/2020.01.02.20016311
Md. Asad Ullah , Bishajit Sarkar , Syed Sajidul Islam

Ebola virus is a highly pathogenic RNA virus that causes haemorrhagic fever in human. With very high mortality rate, Ebola virus is considered as one of the dangerous viruses in the world. Although, the Ebola outbreaks claimed many lives in the past, no satisfactory treatment or vaccine have been discovered yet to fight against Ebola. For this reason, in this study, various tools of bioinformatics and immunoinformatics were used to design possible vaccines against Zaire Ebola virus strain Mayinga-76. To construct the vaccine, three potential antigenic proteins of the virus, matrix protein VP40, envelope glycoprotein and nucleoprotein were selected against which the vaccines would be designed. The MHC class-I, MHC class-II and B-cell epitopes were determined and after robust analysis through various tools and molecular docking analysis, three vaccine candidates, designated as EV-1, EV-2 and EV-3, were constructed. Since the highly conserved epitopes were used for vaccine construction, these vaccine constructs are also expected to be effective on other strains of Ebola virus like strain Gabon-94 and Kikwit-95. Next, the molecular docking study on these vaccine constructs were analyzed by molecular docking study and EV-1 emerged as the best vaccine construct. Later, molecular dynamics simulation study revealed the good performances as well as good stability of the vaccine protein. Finally, codon adaptation and in silico cloning were conducted to design a possible plasmid (pET-19b plasmid vector was used) for large scale, industrial production of the EV-1 vaccine.

中文翻译:

利用反向疫苗学方法设计针对埃博拉病毒的新型亚单位疫苗

埃博拉病毒是一种高致病性的RNA病毒,可引起人类出血热。埃博拉病毒具有很高的死亡率,被认为是世界上的一种危险病毒。尽管埃博拉疫情在过去曾夺去许多生命,但尚未发现令人满意的治疗方法或疫苗来对抗埃博拉。由于这个原因,在这项研究中,使用了多种生物信息学和免疫信息学工具来设计针对扎伊尔埃博拉病毒Mayinga-76菌株的疫苗。为了构建疫苗,选择了三种潜在的病毒抗原蛋白,基质蛋白VP40,包膜糖蛋白和核蛋白,以针对疫苗进行设计。确定了MHC I类,MHC II类和B细胞表位,并通过各种工具和分子对接分析进行了可靠的分析,构建了三个候选疫苗,分别命名为EV-1,EV-2和EV-3。由于高度保守的表位被用于疫苗构建,因此这些疫苗构建体也有望对其他埃博拉病毒株(如Gabon-94和Kikwit-95)有效。接下来,通过分子对接研究分析了这些疫苗构建体的分子对接研究,并且EV-1成为了最佳的疫苗构建体。后来,分子动力学模拟研究揭示了疫苗蛋白的良好性能和稳定性。最后,进行密码子适应和计算机克隆,以设计可能的质粒(使用pET-19b质粒载体),用于大规模工业生产EV-1疫苗。由于高度保守的表位被用于疫苗构建,因此这些疫苗构建体也有望对其他埃博拉病毒株(如Gabon-94和Kikwit-95)有效。接下来,通过分子对接研究分析了这些疫苗构建体的分子对接研究,并且EV-1成为了最佳的疫苗构建体。后来,分子动力学模拟研究揭示了疫苗蛋白的良好性能和稳定性。最后,进行密码子适应和计算机克隆,以设计可能的质粒(使用pET-19b质粒载体),用于大规模工业生产EV-1疫苗。由于高度保守的表位被用于疫苗构建,因此这些疫苗构建体也有望对其他埃博拉病毒株(如Gabon-94和Kikwit-95)有效。接下来,通过分子对接研究分析了这些疫苗构建体的分子对接研究,并且EV-1成为了最佳的疫苗构建体。后来,分子动力学模拟研究揭示了疫苗蛋白的良好性能和稳定性。最后,进行密码子适应和计算机克隆,以设计可能的质粒(使用pET-19b质粒载体),用于大规模工业生产EV-1疫苗。通过分子对接研究对这些疫苗构建体的分子对接研究进行了分析,EV-1成为最好的疫苗构建体。后来,分子动力学模拟研究揭示了疫苗蛋白的良好性能和稳定性。最后,进行密码子适应和计算机克隆,以设计可能的质粒(使用pET-19b质粒载体),用于大规模工业生产EV-1疫苗。通过分子对接研究对这些疫苗构建体的分子对接研究进行了分析,EV-1成为最好的疫苗构建体。后来,分子动力学模拟研究揭示了疫苗蛋白的良好性能和稳定性。最后,进行密码子适应和计算机克隆,以设计可能的质粒(使用pET-19b质粒载体),用于大规模工业生产EV-1疫苗。
更新日期:2020-01-03
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