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反向疫苗学方法用于鉴定和表征作为潜在细胞依赖性和抗体依赖性疫苗候选物的外膜蛋白。

Reverse vaccinology approach for the identification and characterization of outer membrane proteins of as potential cellular- and antibody-dependent vaccine candidates.

作者信息

Leow Chiuan Yee, Kazi Ada, Hisyam Ismail Che Muhammad Khairul, Chuah Candy, Lim Boon Huat, Leow Chiuan Herng, Banga Singh Kirnpal Kaur

机构信息

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Kubang Kerian, Malaysia.

School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia.

出版信息

Clin Exp Vaccine Res. 2020 Jan;9(1):15-25. doi: 10.7774/cevr.2020.9.1.15. Epub 2020 Jan 31.

Abstract

PURPOSE

In the developing world, bacillary dysentery is one of the most common communicable diarrheal infections. There are approximately 169 million cases of shigellosis reported worldwide. The disease is transmitted by a group of Gram-negative intracellular enterobacteria known as , , , and . Conventional treatment regimens for have been less effective due to the development of resistant strains against antibiotics. Therefore, an effective vaccine for the long term control of transmission is urgently needed.

MATERIALS AND METHODS

In this study, a reverse vaccinology approach was employed to identify most conserved and immunogenic outer membrane proteins (OMPs) of 2a.

RESULTS

Five OMPs including fepA, ompC, nlpD_1, tolC, and nlpD_2 were identified as potential vaccine candidates. Protein-protein interactions analysis using STRING software (https://string-db.org/) revealed that five of these OMPs may potentially interact with other intracellular proteins which are involved in beta-lactam resistance pathway. B- and T-cell epitopes of the selected OMPs were predicted using BCPred as well as Propred I and Propred (http://crdd.osdd.net/raghava/propred/), respectively. Each of these OMPs contains regions which are capable to induce B- and T-cell immune responses.

CONCLUSION

Analysis acquired from this study showed that five selected OMPs have great potential for vaccine development against infection. The predicted immunogenic epitopes can also be used for development of peptide vaccines or multi-epitope vaccines against human shigellosis. Reverse vaccinology is a promising strategy for the discovery of potential vaccine candidates which can be used for future vaccine development against global persistent infections.

摘要

目的

在发展中世界,细菌性痢疾是最常见的传染性腹泻感染之一。全球报告的志贺氏菌病病例约有1.69亿例。该疾病由一组革兰氏阴性细胞内肠道杆菌传播,即痢疾志贺氏菌、福氏志贺氏菌、鲍氏志贺氏菌和宋内氏志贺氏菌。由于针对抗生素的耐药菌株的出现,志贺氏菌病的传统治疗方案效果较差。因此,迫切需要一种有效的疫苗来长期控制志贺氏菌的传播。

材料和方法

在本研究中,采用反向疫苗学方法来鉴定福氏志贺氏菌2a最保守和免疫原性的外膜蛋白(OMPs)。

结果

包括fepA、ompC、nlpD_1、tolC和nlpD_2在内的五种OMP被鉴定为潜在的疫苗候选物。使用STRING软件(https://string-db.org/)进行的蛋白质-蛋白质相互作用分析表明,这些OMP中的五种可能与参与β-内酰胺抗性途径的其他细胞内蛋白质相互作用。分别使用BCPred以及Propred I和Propred(http://crdd.osdd.net/raghava/propred/)预测所选OMP的B细胞和T细胞表位。这些OMP中的每一种都包含能够诱导B细胞和T细胞免疫反应的区域。

结论

本研究获得的分析表明,所选的五种OMP在开发针对志贺氏菌感染的疫苗方面具有巨大潜力。预测的免疫原性表位也可用于开发针对人类志贺氏菌病的肽疫苗或多表位疫苗。反向疫苗学是发现潜在疫苗候选物的一种有前途的策略,可用于未来针对全球持续性感染的疫苗开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cabf/7024733/b8ce2f175e52/cevr-9-15-g001.jpg

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