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基于核心蛋白质组学的抗原靶点注释和针对新兴医院感染致病菌的组合免疫原的反向疫苗学辅助设计。

Core-Proteomics-Based Annotation of Antigenic Targets and Reverse-Vaccinology-Assisted Design of Ensemble Immunogen against the Emerging Nosocomial Infection-Causing Bacterium .

机构信息

Center for Biotechnology and Microbiology, University of Swat, Swat 19200, Khyber Pakhtunkhwa, Pakistan.

Nishtar Medical College, Multan 59300, Punjab, Pakistan.

出版信息

Int J Environ Res Public Health. 2021 Dec 24;19(1):194. doi: 10.3390/ijerph19010194.

DOI:10.3390/ijerph19010194
PMID:35010455
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8750920/
Abstract

is a ubiquitous Gram-negative emerging pathogen that causes hospital-acquired infection in both immunocompromised and immunocompetent patients. It is a multi-drug-resistant bacterium; therefore, an effective subunit immunogenic candidate is of great interest to encounter the pathogenesis of this pathogen. A protein-wide annotation of immunogenic targets was performed to fast-track the vaccine development against this pathogen, and structural-vaccinology-assisted epitopes were predicted. Among the total proteins, only three, A0A1T3FLU2, A0A1T3INK9, and A0A1V3U124, were shortlisted, which are the essential vaccine targets and were subjected to immune epitope mapping. The linkers EAAK, AAY, and GPGPG were used to link CTL, HTL, and B-cell epitopes and an adjuvant was also added at the N-terminal to design a multi-epitope immunogenic construct (MEIC). The computationally predicted physiochemical properties of the ensemble immunogen reported a highly antigenic nature and produced multiple interactions with immune receptors. In addition, the molecular dynamics simulation confirmed stable binding and good dynamic properties. Furthermore, the computationally modeled immune response proposed that the immunogen triggered a strong immune response after several doses at different intervals. Neutralization of the antigen was observed on the 3rd day of injection. Conclusively, the immunogenic construct produces protection against ; however, further immunological testing is needed to unveil its real efficacy.

摘要

是一种普遍存在的革兰氏阴性新兴病原体,可导致免疫功能低下和免疫功能正常的患者发生医院获得性感染。它是一种多药耐药菌;因此,寻找有效的亚单位免疫原性候选物对于应对这种病原体的发病机制非常重要。对免疫原性靶标的蛋白质进行了广泛注释,以加速针对该病原体的疫苗开发,并预测了结构疫苗学辅助表位。在总蛋白中,只有 A0A1T3FLU2、A0A1T3INK9 和 A0A1V3U124 这三种蛋白被列为短名单,它们是必不可少的疫苗靶点,并进行了免疫表位作图。使用 EAAK、AAY 和 GPGPG 接头连接 CTL、HTL 和 B 细胞表位,并在 N 端添加佐剂来设计多表位免疫原性构建体 (MEIC)。组合免疫原的计算预测的物理化学性质报告具有高度的抗原性,并与免疫受体产生多种相互作用。此外,分子动力学模拟证实了稳定的结合和良好的动力学特性。此外,计算建模的免疫反应表明,免疫原在不同间隔的几次剂量后引发了强烈的免疫反应。在注射后的第 3 天观察到抗原的中和作用。总之,免疫原构建体对产生了保护作用;然而,需要进一步的免疫学测试来揭示其真正的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/6861a4c2c92b/ijerph-19-00194-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/73099b65a7c2/ijerph-19-00194-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/6f618052b881/ijerph-19-00194-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/dc28167c7ee5/ijerph-19-00194-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/8e68e0b3daa9/ijerph-19-00194-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/ebd8352d5964/ijerph-19-00194-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/06de1e339823/ijerph-19-00194-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/01a5f30ea28f/ijerph-19-00194-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/88127ecce53a/ijerph-19-00194-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/6861a4c2c92b/ijerph-19-00194-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/73099b65a7c2/ijerph-19-00194-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/6f618052b881/ijerph-19-00194-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/dc28167c7ee5/ijerph-19-00194-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/8e68e0b3daa9/ijerph-19-00194-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/ebd8352d5964/ijerph-19-00194-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/06de1e339823/ijerph-19-00194-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/01a5f30ea28f/ijerph-19-00194-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/88127ecce53a/ijerph-19-00194-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/8750920/6861a4c2c92b/ijerph-19-00194-g009.jpg

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