Design of a multi-epitope-based vaccine targeting M-protein of SARS-CoV2: an immunoinformatics approach
Design of a multi-epitope-based vaccine targeting M-protein of SARS-CoV2: an immunoinformatics approach
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DOI：
10.1080/07391102.2020.1850357
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发表时间：
2020-11-16
影响因子：
4.4
通讯作者：
Srirama, Krupanidhi
中科院分区：
文献类型：
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作者：
Ayyagari, Vijaya Sai;Venkateswarulu, T. C.;Srirama, Krupanidhi
本研究选择冠状病毒包膜蛋白膜糖蛋白（M）作为靶点，通过免疫信息学方法设计多表位疫苗。用于构建疫苗的B细胞和T细胞表位具有抗原性、非过敏性和无毒性。佐剂、β-防御素和PADRE序列包括在疫苗的N-末端。所有表位通过接头连接以降低连接免疫原性。评价了疫苗的各种理化参数。预测疫苗构建体的二级和三级结构。三级结构进一步细化，并通过使用不同的工具验证与蛋白质结构细化相关的各种参数。B细胞诱导的体液免疫依赖于疫苗构建体表面抗原决定簇的鉴定。在这方面，发现疫苗构建体在其三维构象中由几个B细胞表位组成。将疫苗与TLR-3受体进行分子对接，以研究它们的结合及其强度。此外，使用LigPlot+可视化对接复合物中的蛋白质-蛋白质相互作用。人口覆盖率分析表明，多表位疫苗覆盖了全球94.06%的人口。将该疫苗构建体通过计算机模拟成功地克隆到pET-28 a（+）中。免疫模拟研究显示，诱导了初级、二级和三级免疫应答，其特征是抗体、INF-γ、IL-2、TGF-β、B-细胞、CD 4+和CD 8+细胞水平增加。最后，疫苗构建体能够如所期望的那样引发免疫应答。Sarma
In the present study, one of the targets present on the envelopes of coronaviruses, membrane glycoprotein (M) was chosen for the design of a multi-epitope vaccine by Immunoinformatics approach. The B-cell and T-cell epitopes used for the construction of vaccine were antigenic, nonallergic and nontoxic. An adjuvant, beta-defensin and PADRE sequence were included at the N-terminal end of the vaccine. All the epitopes were joined by linkers for decreasing the junctional immunogenicity. Various physicochemical parameters of the vaccine were evaluated. Secondary and tertiary structures were predicted for the vaccine construct. The tertiary structure was further refined, and various parameters related to the refinement of the protein structure were validated by using different tools. Humoral immunity induced by B-cells relies upon the identification of antigenic determinants on the surface of the vaccine construct. In this regard, the vaccine construct was found to consist of several B-cell epitopes in its three-dimensional conformation. Molecular docking of the vaccine was carried out with TLR-3 receptor to study their binding and its strength. Further, protein-protein interactions in the docked complex were visualized using LigPlot+. Population coverage analysis had shown that the multi-epitope vaccine covers 94.06% of the global population. The vaccine construct was successfully cloned in silico into pET-28a (+). Immune simulation studies showed the induction of primary, secondary and tertiary immune responses marked by the increased levels of antibodies, INF-gamma, IL-2, TGF-beta, B- cells, CD4+ and CD8+ cells. Finally, the vaccine construct was able to elicit immune response as desired.Communicated by Ramaswamy H. Sarma