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利用具有高度抗原性的 PE-PGRS 家族蛋白开发肽疫苗候选物,以刺激宿主对 HRv 的免疫反应:一种免疫信息学方法。

Development of peptide vaccine candidate using highly antigenic PE-PGRS family proteins to stimulate the host immune response against HRv: an immuno-informatics approach.

机构信息

CSIR-Institute of Genomics and Integrative Biology, Delhi, India.

Academy of Scientific and Innovative Research (AcSIR), CSIR-HRDC, Ghaziabad, Uttar Pradesh, India.

出版信息

J Biomol Struct Dyn. 2023 May;41(8):3382-3404. doi: 10.1080/07391102.2022.2048079. Epub 2022 Mar 16.

DOI:10.1080/07391102.2022.2048079
PMID:35293852
Abstract

Tuberculosis (TB) is a fast spreading; transmissible disease caused by the (). has a high death rate in its endemic regions due to a lack of appropriate treatment and preventative measures. We have used a vaccinomics strategy to create an effective multi-epitope vaccine against . The antigenic proteins with the highest antigenicity were utilised to predict cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and linear B-lymphocyte (LBL) epitopes. CTL and HTL epitopes were covered in 99.97% of the population. Seven epitopes each of CTL, HTL, and LBL were ultimately selected and utilised to develop a multi-epitope vaccine. A vaccine design was developed by combining these epitopes with suitable linkers and LprG adjuvant. The vaccine chimera was revealed to be highly immunogenic, non-allergenic, and non-toxic. To ensure a better expression within the K12 ( K12) host system, codon adaptation and in silico cloning were accomplished. Following that, various validation studies were conducted, including molecular docking, molecular dynamics simulation, and immunological simulation, all of which indicated that the designed vaccine would be stable in the biological environment and effective against infection. The immune simulation revealed higher levels of T-cell and B-cell activity, which corresponded to the actual immune response. Exposure simulations were repeated several times, resulting in increased clonal selection and faster antigen clearance. These results suggest that, if proposed vaccine chimera would test both in-vitro and in-vivo, it could be a viable treatment and preventive strategy for TB.Communicated by Ramaswamy H. Sarma.

摘要

结核病(TB)是一种传播迅速的传染病,由()引起。由于缺乏适当的治疗和预防措施,在流行地区的死亡率很高。我们使用疫苗组学策略来创建一种有效的针对多表位疫苗。利用具有最高抗原性的抗原蛋白来预测细胞毒性 T 淋巴细胞(CTL)、辅助 T 淋巴细胞(HTL)和线性 B 淋巴细胞(LBL)表位。CTL 和 HTL 表位涵盖了 99.97%的人群。最终选择并利用了 7 个 CTL、HTL 和 LBL 表位来开发多表位疫苗。通过将这些表位与合适的接头和 LprG 佐剂结合,设计了一种疫苗。疫苗嵌合体被证明具有高度的免疫原性、非变应原性和非毒性。为了确保在宿主系统中更好地表达,进行了密码子适应和计算机克隆。之后,进行了各种验证研究,包括分子对接、分子动力学模拟和免疫模拟,所有这些都表明设计的疫苗在生物环境中是稳定的,并且对感染有效。免疫模拟显示 T 细胞和 B 细胞的活性更高,与实际的免疫反应相对应。暴露模拟重复进行了多次,导致克隆选择增加和抗原清除更快。这些结果表明,如果提出的疫苗嵌合体在体外和体内都进行测试,它可能成为结核病的一种可行的治疗和预防策略。由 Ramaswamy H. Sarma 传达。

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