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利用免疫信息学方法,筛选大别山病毒(SFTS)蛋白质组中的免疫表位,设计一种针对蛋白质和蛋白质组的疫苗,以诱导免疫反应。

Screening of immune epitope in the proteome of the Dabie bandavirus, SFTS, to design a protein-specific and proteome-wide vaccine for immune response instigation using an immunoinformatics approaches.

机构信息

Centre for Biotechnology and Microbiology, University of Swat, Khyber Pakhtunkhwa, Pakistan.

Nawaz Sharif Medical College, Gujrat, Punjab, Pakistan.

出版信息

Comput Biol Med. 2022 Sep;148:105893. doi: 10.1016/j.compbiomed.2022.105893. Epub 2022 Aug 7.

Abstract

Tick-borne viruses are a major risk from tick bites, which could result in viral infectious diseases among animals and humans. Bunyavirus causes severe fever with thrombocytopenia syndrome (SFTS), with signs and symptoms including high fever, vomiting, diarrhea, thrombocytopenia (low platelet count), leukopenia (low white blood cell count), elevated liver enzyme levels, multiple organ failure, and has a 6%-30% case-fatality rate. To date no effective drug or vaccines are available thus need urgent research for therapeutics formulation. Hence, in this study, the computational meta-analysis approach was implemented that incorporates immunoinformatics to find potential B-cell, HTL (helper T lymphocytes) and T-cell epitopes derived from antigenic SFTS proteins to design multi-epitopes vaccines for the treatment of SFTS. The predicted T cell, B cell and HTL epitopes were shortlisted and checked for antigenic properties and allergenic features. The best epitopes were then joined together to model of multi-epitopes vaccines for specific proteins (replicase and glycoprotein) and proteome wide. The constructed models were validated using in silico molecular docking approach to evaluate binding potential of the designed best constructs with TLR3 (toll like receptor 3). Following the MEVC (multi-epitopes vaccine construct) injection, the response of the immune system was significantly stimulated, and anti-toxicity of induced antibodies was tremendously enhanced. Before being neutralized, the antigen titers remained high 5-10 days after injection of replicase, glycoprotein and proteome wide constructed vaccines. For each antigenic vaccine, a significant antibody response induction was observed. Further, in vivo trials are required to affirm the effectiveness of the constructed vaccine against SFTS.

摘要

蜱传病毒是由蜱叮咬引起的主要风险,可能导致动物和人类的病毒性传染病。布尼亚病毒引起严重发热伴血小板减少综合征(SFTS),其症状和体征包括高热、呕吐、腹泻、血小板减少(血小板计数低)、白细胞减少(白细胞计数低)、肝酶水平升高、多器官衰竭,病死率为 6%-30%。迄今为止,尚无有效的药物或疫苗可用,因此需要紧急研究治疗方法。因此,在这项研究中,我们采用了计算综合分析方法,结合免疫信息学,从抗原性 SFTS 蛋白中寻找潜在的 B 细胞、HTL(辅助 T 淋巴细胞)和 T 细胞表位,设计用于治疗 SFTS 的多表位疫苗。预测的 T 细胞、B 细胞和 HTL 表位被筛选出来,并检查其抗原性和变应原性特征。然后将最佳表位连接起来,为特定蛋白质(复制酶和糖蛋白)和蛋白质组设计多表位疫苗。使用计算机分子对接方法对构建的模型进行验证,以评估设计的最佳构建体与 TLR3( toll 样受体 3)的结合潜力。在进行 MEVC(多表位疫苗构建)注射后,免疫系统的反应得到了显著刺激,诱导抗体的抗毒性得到了极大增强。在复制酶、糖蛋白和蛋白质组构建疫苗注射后 5-10 天,抗原滴度在被中和之前仍保持高水平。对于每种抗原性疫苗,都观察到了显著的抗体反应诱导。此外,还需要进行体内试验来证实构建疫苗对 SFTS 的有效性。

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