开发针对人类 SARS 冠状病毒-2 的新型多位点 DNA 疫苗:免疫形式设计研究。

Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2022-06-23 eCollection Date: 2022-01-01 DOI:10.55730/1300-0152.2615
Afshin Samimi Nemati, Sako Mirzaie, Mohammad Reza Masoumian, Fatemeh Sheikhi, Mostafa Jamalan
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摘要

人类严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2)导致了当前 COVID-19 在全球的流行。目前,针对 COVID-19 的高效疫苗的生产正在进行深入研究。在这项研究中,我们利用反向疫苗学和 DNA 疫苗方法设计了一种新型多位点 DNA 疫苗来预防 SARS-CoV-2。采用这些策略不仅缩短了疫苗开发的时间,降低了成本,还提高了疫苗的免疫保护特性。为此,我们选择了 SARS-CoV-2 的核壳蛋白、膜糖蛋白和 ORF8 蛋白的表位作为 B 细胞和 T 细胞受体的靶标。因此,对所选表位的 DNA 序列进行了优化,以便在真核系统中表达蛋白质。为此,在表位序列中加入了 Kozak 和组织纤溶酶原激活剂序列,以分别实现适当的蛋白质表达和分泌。此外,还在设计的 DNA 疫苗中加入了白细胞介素-2 和 beta-defensin 1 前蛋白序列作为佐剂。根据同源多肽的同源建模,对由 SARS-CoV-2 多表位抗原组成的融合蛋白(fuspMA)进行了建模和改进,然后在 50 ns 的分子动力学模拟中对构建的 fuspMA 三维模型进行了进一步研究。进一步的生物信息学预测表明,fuspMA 是一种稳定的蛋白质,具有可接受的抗原特征,没有过敏性或毒性特征。最后,通过分子对接程序验证了 fuspMA 与 MHC I、II 和 TLRs 分子的亲和性。总之,经过更多的体内评估后,所设计的多位点 DNA 疫苗似乎有机会成为一种有效的 COVID-19 疫苗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Development a novel multiepitope DNA vaccine against human SARS coronavirus-2: an immunoinformatic designing study.

Human SARS coronavirus 2 (SARS-CoV-2) causes the current global COVID-19 pandemic. The production of an efficient vaccine against COVID-19 is under heavy investigation. In this study, we have designed a novel multiepitope DNA vaccine against SARS-CoV-2 using reverse vaccinology and DNA vaccine approaches. Applying these strategies led to reduce the time and costs of vaccine development and also improve the immune protective characteristics of the vaccine. For this purpose, epitopes of nucleocapsid, membrane glycoprotein, and ORF8 proteins of SARS-CoV-2 chose as targets for B and T-cell receptors. Accordingly, DNA sequences of selected epitopes have optimized for protein expression in the eukaryotic system. To this end, the Kozak and tissue plasminogen activator sequences were added into the epitope sequences for proper protein expression and secretion, respectively. Furthermore, interleukin-2 and beta-defensin 1 preproprotein sequences were incorporated to the designed DNA vaccine as an adjuvant. Modeling and refinement of fused protein composed of SARS-CoV-2 multiepitope antigens (fuspMA) have performed based on homology modeling of orthologous peptides, then constructed 3D model of fuspMA was more investigated during 50 ns of molecular dynamics simulation. Further bioinformatics predictions demonstrated that fuspMA is a stable protein with acceptable antigenic features and no allergenicity or toxicity characteristics. Finally, the affinity of fuspMA to the MHC I and II and TLRs molecules validated by the molecular docking procedure. In conclusion, it seems the designed multiepitope DNA vaccine could have a chance to be introduced as an efficient vaccine against COVID-19 after more in vivo evaluations.

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