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基于计算机减法蛋白质组分析设计针对……的多表位亚单位疫苗

In Silico Subtractive Proteome Analysis to Design Multi-Epitope-Based Subunit Vaccine against .

作者信息

AlMalki Fatemah

机构信息

Fatemah AlMalki, Biology Department, College of Science and Humanities- Al Quwaiiyah, Shaqra University, Al Quwaiiyah 19257, Saudi Arabia.

出版信息

J Microbiol Biotechnol. 2024 Nov 25;35:e2410015. doi: 10.4014/jmb.2410.10015.

DOI:10.4014/jmb.2410.10015
PMID:39809513
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11813342/
Abstract

is a gram-negative, facultatively anaerobic bacterium typically found in the oropharynx and respiratory tract of humans. It is responsible for various infections, including head-and-neck infections, pericarditis, and abscesses of the deltoid, perirenal tissue, brain, and liver. Increasing antibiotic resistance requires urgent identification of novel drug targets to fight this bacterium. In this study, subtractive proteomics and immunoinformatics approaches were used to identify the most suitable candidates for multi-epitope vaccine development. A non-homologous and pathogenic protein, penicillin-binding protein 1A (PBP1A), was identified after extracting the entire proteome sequence of NCTC 10596. PBP1A is antigenic and necessary for pathogen survival. Helper T-cell (HTL), cytotoxic T-cell (CTL), and B-cell lymphocyte-inducing epitopes were integrated through immunoinformatic methods and rigorous immunological screening processes. Various physicochemical, allergenic, and antigenic properties were also evaluated to ensure the safety and immunogenicity of the vaccine candidates. Dynamic modeling and molecular docking techniques were used to examine the molecular interactions, thermodynamic stability, and binding affinities. The vaccine demonstrated a robust and consistent interaction with Toll-like receptors (TLRs), and its potential to elicit an immunological response was evaluated in silico. For in silico cloning, the final vaccine candidates were back-translated and cloned into an host to achieve high expression of the predicted protein. Computational analyses suggested that the proposed vaccine candidate shows promise for combating bacterial infections and eliciting a robust immune response. However, experimental validation is crucial to authenticate the precise safety and immunogenicity profiles of this vaccine.

摘要

是一种革兰氏阴性兼性厌氧菌,通常存在于人类的口咽和呼吸道中。它可引发多种感染,包括头颈部感染、心包炎以及三角肌、肾周组织、脑和肝脏的脓肿。抗生素耐药性的增加迫切需要确定新的药物靶点来对抗这种细菌。在本研究中,采用消减蛋白质组学和免疫信息学方法来确定多表位疫苗开发的最合适候选物。在提取NCTC 10596的完整蛋白质组序列后,鉴定出一种非同源致病蛋白,即青霉素结合蛋白1A(PBP1A)。PBP1A具有抗原性,是病原体生存所必需的。通过免疫信息学方法和严格的免疫学筛选过程,整合了辅助性T细胞(HTL)、细胞毒性T细胞(CTL)和B淋巴细胞诱导表位。还评估了各种物理化学、致敏和抗原特性,以确保候选疫苗的安全性和免疫原性。使用动态建模和分子对接技术来研究分子相互作用、热力学稳定性和结合亲和力。该疫苗与Toll样受体(TLR)表现出强大且一致的相互作用,并在计算机模拟中评估了其引发免疫反应的潜力。对于计算机克隆,将最终的候选疫苗反向翻译并克隆到宿主中,以实现预测蛋白的高表达。计算分析表明,所提出的候选疫苗在对抗细菌感染和引发强大免疫反应方面显示出前景。然而,实验验证对于验证该疫苗的确切安全性和免疫原性至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/0042920bbea3/jmb-35-e2410015-f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/ead92a6a59f3/jmb-35-e2410015-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/12b6c21e31f4/jmb-35-e2410015-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/7652cdf570c6/jmb-35-e2410015-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/660c3df04e36/jmb-35-e2410015-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/8af2ca847d39/jmb-35-e2410015-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/c6e59821d693/jmb-35-e2410015-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/87c3554f9034/jmb-35-e2410015-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/7b58440b7041/jmb-35-e2410015-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/1581f49d9741/jmb-35-e2410015-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/0042920bbea3/jmb-35-e2410015-f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/ead92a6a59f3/jmb-35-e2410015-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/12b6c21e31f4/jmb-35-e2410015-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/7652cdf570c6/jmb-35-e2410015-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/660c3df04e36/jmb-35-e2410015-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/8af2ca847d39/jmb-35-e2410015-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/c6e59821d693/jmb-35-e2410015-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/87c3554f9034/jmb-35-e2410015-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/7b58440b7041/jmb-35-e2410015-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/1581f49d9741/jmb-35-e2410015-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/11813342/0042920bbea3/jmb-35-e2410015-f10.jpg

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