Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches
Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches
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DOI：
10.3389/fimmu.2020.01784
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发表时间：
2020-07-28
影响因子：
7.3
通讯作者：
Zha, Yan
中科院分区：
文献类型：
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作者：
Dong, Rong;Chu, Zhugang;Zha, Yan
COVID-19最近已成为对公共卫生的最严重威胁，其患病率正以惊人的速度增长。病毒的潜伏期约为1至14天，所有年龄组别的人都可能感染，死亡率约为5.9%。COVID-19是由一种新型单链正（+）义RNA β冠状病毒引起的。SARS-CoV-2疫苗的开发是全世界的迫切需要。免疫信息学方法既具有成本效益又方便，因为计算机预测可以减少所需的实验数量。在本研究中，我们借助免疫信息学工具，尝试设计一种可用于预防和治疗COVID-19的多表位疫苗。根据SARS-CoV-2的蛋白质，利用B细胞、细胞毒性T淋巴细胞（CTL）和辅助性T淋巴细胞（HTL）计算抗原表位。通过用接头将B细胞、HTL和CTL表位融合在一起来设计疫苗。为了增强免疫原性，在EAAAK接头的帮助下，将β-防御素（45 mer）氨基酸序列和泛HLA DR结合表位（13 aa）邻接到疫苗的N-末端。为了使模型疫苗能够在细胞内递送，将达特序列（11 aa）附加到C-末端。接头在产生延伸的构象（柔性）、蛋白质折叠和功能结构域的分离中起着至关重要的作用，因此，使蛋白质结构更加稳定。然后预测最终疫苗的二级和三维（3D）结构。此外，通过分子对接评估最终疫苗与免疫受体（toll样受体-3（TLR-3）、主要组织相容性复合物（MHC-I）和MHC-II）之间的复合物。最后，为了确认所设计的疫苗的表达，在Java密码子适应工具的帮助下增强疫苗的mRNA，并从Mfold生成二级结构。然后我们进行了硅克隆。最终的疫苗需要实验验证，以确定其控制SARS-CoV-2感染的安全性和有效性。
COVID-19 has recently become the most serious threat to public health, and its prevalence has been increasing at an alarming rate. The incubation period for the virus is similar to 1-14 days and all age groups may be susceptible to a fatality rate of about 5.9%. COVID-19 is caused by a novel single-stranded, positive (+) sense RNA beta coronavirus. The development of a vaccine for SARS-CoV-2 is an urgent need worldwide. Immunoinformatics approaches are both cost-effective and convenient, asin silicopredictions can reduce the number of experiments needed. In this study, with the aid of immunoinformatics tools, we tried to design a multi-epitope vaccine that can be used for the prevention and treatment of COVID-19. The epitopes were computed by using B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) base on the proteins of SARS-CoV-2. A vaccine was devised by fusing together the B cell, HTL, and CTL epitopes with linkers. To enhance the immunogenicity, the beta-defensin (45 mer) amino acid sequence, and pan-HLA DR binding epitopes (13aa) were adjoined to the N-terminal of the vaccine with the help of the EAAAK linker. To enable the intracellular delivery of the modeled vaccine, a TAT sequence (11aa) was appended to C-terminal. Linkers play vital roles in producing an extended conformation (flexibility), protein folding, and separation of functional domains, and therefore, make the protein structure more stable. The secondary and three-dimensional (3D) structure of the final vaccine was then predicted. Furthermore, the complex between the final vaccine and immune receptors (toll-like receptor-3 (TLR-3), major histocompatibility complex (MHC-I), and MHC-II) were evaluated by molecular docking. Lastly, to confirm the expression of the designed vaccine, the mRNA of the vaccine was enhanced with the aid of the Java Codon Adaptation Tool, and the secondary structure was generated from Mfold. Then we performedin silicocloning. The final vaccine requires experimental validation to determine its safety and efficacy in controlling SARS-CoV-2 infections.