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设计一种基于外膜蛋白(Omp-W)的疫苗,以免疫对抗 和 :一种计算机模拟方法。

Designing an Outer Membrane Protein (Omp-W) Based Vaccine for Immunization against and : An in silico Approach.

机构信息

Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

Cellular and Molecular Research Center, Research Institute on Cellular and Molecular Medicine, Urmia University of Medical Sciences, Urmia, Iran

出版信息

Recent Pat Biotechnol. 2020;14(4):312-324. doi: 10.2174/1874609813666200929113341.

DOI:10.2174/1874609813666200929113341
PMID:32990553
Abstract

BACKGROUND

Cholera triggered by Vibrio cholerae remains the main reason for morbidity and mortality all over the world. In addition, salmonellosis is regarded as an infectious disease that makes it essential for the identification and detection of Salmonella. With a beta-barrel structure consisting of eight non-parallel beta strands, OmpW family is widely distributed among gram-negative bacteria. Moreover, OmpW isolated from S. typhimurium and Vibrio cholerae can be used in vaccine design.

METHODS

Topology prediction was determined. T-cell and B-cell epitopes were selected from exposed areas, and sequence conservancy was evaluated. The remaining loops and inaccessible residues were removed to prepare OmpW-1. High antigenicity peptides were detected to replace inappropriate residues to obtain OmpW-2. Physicochemical properties were assessed, and antigenicity, hydrophobicity, flexibility, and accessibility were compared to the native Omp-W structure. Low score areas were removed from the designed structure for preparing the OmpW-3. To construct OmpW-4, TTFrC was used as T-CD4+ cell-stimulating factor and CTB as adjuvant to the end of the C-terminal of this sequence, which can increase the antigenicity and sequence density. The sequences were re-analyzed to delete the unfavorable residues. Besides, the solubility of the mature OmpW and the designed structure were predicted while overexpressed in E. coli.

RESULTS

The designed vaccine is a stable protein that has immune cells recognizing epitopes and is considered as an antigen. The construct can be overexpressed in an E. coli.

CONCLUSION

The multi-epitope vaccine is a suitable stimulator for the immune system and would be a candidate for experimental research. Recent patents describe numerous inventions related to the clinical facets of vaccine peptide against human infectious disease.

摘要

背景

由霍乱弧菌引起的霍乱仍然是全世界发病率和死亡率的主要原因。此外,沙门氏菌病被认为是一种传染病,因此有必要对沙门氏菌进行鉴定和检测。OmpW 家族由八个非平行的β链组成,具有β桶结构,广泛分布于革兰氏阴性菌中。此外,从鼠伤寒沙门氏菌和霍乱弧菌中分离的 OmpW 可用于疫苗设计。

方法

进行拓扑预测。从暴露区域中选择 T 细胞和 B 细胞表位,并评估序列保守性。去除剩余的环和不可接近的残基,以制备 OmpW-1。检测高抗原性肽以取代不合适的残基,得到 OmpW-2。评估理化性质,并比较抗原性、疏水性、柔韧性和可及性与天然 Omp-W 结构。从设计结构中去除低评分区域以制备 OmpW-3。为了构建 OmpW-4,TTFrC 被用作 T-CD4+细胞刺激因子,CTB 作为该序列 C 末端的佐剂,这可以增加抗原性和序列密度。重新分析序列以删除不利的残基。此外,预测成熟 OmpW 和设计结构在大肠杆菌中过表达时的溶解度。

结果

设计的疫苗是一种稳定的蛋白质,具有免疫细胞识别表位的能力,被认为是一种抗原。该构建体可在大肠杆菌中过表达。

结论

多表位疫苗是免疫系统的一种合适刺激物,将成为实验研究的候选者。最近的专利描述了许多与人类传染病疫苗肽的临床方面相关的发明。

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