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运用免疫信息学方法设计针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的多表位肽疫苗候选物。

Designing multi-epitope based peptide vaccine candidates against SARS-CoV-2 using immunoinformatics approach.

作者信息

Ysrafil Ysrafil, Sapiun Zulfiayu, Astuti Indwiani, Anasiru Mohammad Anas, Slamet Nangsih Sulastri, Hartati Hartati, Husain Fadli, Damiti Sukmawati Ahmad

机构信息

Faculty of Medicine, Universitas Palangka Raya, Palangka Raya 73111, Indonesia.

Department of Pharmacy, Health Polytechnic of Gorontalo, Gorontalo 96135, Indonesia.

出版信息

Bioimpacts. 2022;12(4):359-370. doi: 10.34172/bi.2022.23769. Epub 2022 Feb 27.

DOI:10.34172/bi.2022.23769
PMID:35975206
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9376164/
Abstract

The current incidence of the novel coronavirus disease has shown only small reductions of cases and has become a major public health challenge. Development of effective vaccines against the virus is still being encouraged such as multi-epitope vaccines designed from the components of SARS-CoV-2 including its spike, nucleocapsid and ORF1a proteins. Since the addition of adjuvants including HABA protein and L7/L12 ribosomal are considered helpful to increase the effectiveness of the designed vaccine, we proposed to design multiepitope vaccines by two different adjuvants. We used the IEDB server to predict BCL and TCL epitopes that were characterized using online tools including VaxiJen, AllPred and IL-10 Prediction. The selected epitopes were further constructed into multiepitope vaccines. We also added two different adjuvants to the vaccine components in order to increase the effectiveness of the vaccines. The 3D-structured vaccines were built using trRosetta. They were further docked with different Toll-like-receptors (TLR 3, 4 and 8) and the entry receptor of SARS-CoV-2, ACE2 using ClusPro, PatchDock and refined by FireDock. All structures were visualized by USCF Chimera and PyMOL. In this study, we succeeded in designing two different candidate vaccines by the addition of HABA protein and L7/L12 ribosomal as adjuvants. The two vaccines were almost equally good in terms of their physicochemical properties and characteristics. Likewise, their strong interactions with TLR3 4, 8 and ACE2 show the lowest energy level of both was estimated at more than -1,000. Interactions of vaccines with ACE2 and TLRs are essential for activation of immune responses and production of antibodies. The two designed and constructed multiepitope vaccine have good characteristics and may have the potential to activate humoral and cellular immune responses against SARS-CoV-2. Further research is worth considering to confirm the findings of this study.

摘要

新型冠状病毒病目前的发病率仅略有下降,已成为一项重大的公共卫生挑战。仍在鼓励研发针对该病毒的有效疫苗,例如从严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的成分(包括其刺突蛋白、核衣壳蛋白和开放阅读框1a蛋白)设计的多表位疫苗。由于添加包括HABA蛋白和L7/L12核糖体在内的佐剂被认为有助于提高所设计疫苗的有效性,我们提议通过两种不同的佐剂设计多表位疫苗。我们使用免疫表位数据库(IEDB)服务器预测B细胞表位(BCL)和T细胞表位(TCL),这些表位通过包括VaxiJen、AllPred和白细胞介素-10预测在内的在线工具进行表征。所选表位进一步构建成多表位疫苗。我们还在疫苗成分中添加了两种不同的佐剂,以提高疫苗的有效性。使用trRosetta构建3D结构的疫苗。它们进一步与不同的Toll样受体(TLR 3、4和8)以及SARS-CoV-2的进入受体血管紧张素转换酶2(ACE2)对接,使用ClusPro、PatchDock并通过FireDock进行优化。所有结构通过美国加利福尼亚大学旧金山分校(USCF)的Chimera和PyMOL进行可视化。在本研究中,我们成功地通过添加HABA蛋白和L7/L12核糖体作为佐剂设计了两种不同的候选疫苗。这两种疫苗在物理化学性质和特征方面几乎同样良好。同样,它们与TLR3、4、8和ACE2的强相互作用表明两者的最低能量水平估计超过 -1000。疫苗与ACE2和TLR的相互作用对于激活免疫反应和产生抗体至关重要。所设计和构建的两种多表位疫苗具有良好的特性,可能具有激活针对SARS-CoV-2的体液免疫和细胞免疫反应的潜力。值得进一步研究以证实本研究的结果。

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