Contriving a chimeric polyvalent vaccine to prevent infections caused by herpes simplex virus (type-1 and type-2): an exploratory immunoinformatic approach
Contriving a chimeric polyvalent vaccine to prevent infections caused by herpes simplex virus (type-1 and type-2): an exploratory immunoinformatic approach
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DOI：
10.1080/07391102.2019.1647286
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发表时间：
2019-08-09
影响因子：
4.4
通讯作者：
Hasan, Md Nazmul
中科院分区：
文献类型：
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作者：
Hasan, Mahmudul;Islam, Shiful;Hasan, Md Nazmul
单纯疱疹病毒1型(HSV-1)和单纯疱疹病毒2型(HSV-2)可引起多种感染，包括口腔面部感染、生殖器疱疹、疱疹角膜炎、皮肤感染等。到目前为止，FDA批准的许可HSV疫苗还没有上市。因此，本研究旨在鉴定和鉴定一种有效的基于表位的针对这两种单纯疱疹病毒的多价疫苗。通过与MHC-I、II类分子的结合分析、抗原性筛选、跨膜拓扑筛选、致敏性和毒性评价、群体覆盖率分析和分子对接方法，对所选蛋白进行鉴定，以设计高抗原性表位。最终的疫苗是由每个蛋白的顶端CTL、HTL和BCL表位以及合适的佐剂和连接子组成的。进一步利用理化和二级结构分析、二硫键工程、分子动力学模拟和密码子适配等手段，研制出一种独特的多表位多肽疫苗。对精制疫苗结构与不同MHC分子和人免疫TLR-2受体的对接分析表明，它们之间存在较高的相互作用。模型疫苗和TLR-2的复杂结构在分子水平上表现出最小的变形性。此外，利用pET28a(+)载体对大肠杆菌K12株进行了翻译效价和微生物表达的分析，构建的疫苗结构与整个人类蛋白质组没有相似性。这项研究使设计出一种新的嵌合多价疫苗能够对两种HSV血清型产生广泛的免疫力。然而，强烈建议使用模型动物进行进一步的湿实验室研究，以从实验上验证我们的发现。拉马斯瓦米·H·萨尔马沟通
Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) cause a variety of infections including oral-facial infections, genital herpes, herpes keratitis, cutaneous infection and so on. To date, FDA-approved licensed HSV vaccine is not available yet. Hence, the study was conducted to identify and characterize an effective epitope based polyvalent vaccine against both types of Herpes Simplex Virus. The selected proteins were retrieved from ViralZone and assessed to design highly antigenic epitopes by binding analyses of the peptides with MHC class-I and class-II molecules, antigenicity screening, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach. The final vaccine was constructed by the combination of top CTL, HTL and BCL epitopes from each protein along with suitable adjuvant and linkers. Physicochemical and secondary structure analysis, disulfide engineering, molecular dynamic simulation and codon adaptation were further employed to develop a unique multi-epitope peptide vaccine. Docking analysis of the refined vaccine structure with different MHC molecules and human immune TLR-2 receptor demonstrated higher interaction. Complexed structure of the modeled vaccine and TLR-2 showed minimal deformability at molecular level. Moreover, translational potency and microbial expression of the modeled vaccine was analyzed with pET28a(+) vector for E. coli strain K12 and the vaccine constructs had no similarity with entire human proteome. The study enabled design of a novel chimeric polyvalent vaccine to confer broad range immunity against both HSV serotypes. However, further wet lab based research using model animals are highly recommended to experimentally validate our findings. Communicated by Ramaswamy H. Sarma