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全基因组筛选疫苗靶标优先级和反向疫苗学辅助设计肽疫苗以增强对空肠弯曲菌的体液免疫反应。

Genome-wide screening of vaccine targets prioritization and reverse vaccinology aided design of peptides vaccine to enforce humoral immune response against Campylobacter jejuni.

机构信息

Center for Biotechnology and Microbiology, University of Swat, Kanju Campus, Swat, Pakistan.

Advanced Drug Delivery Laboratory, Pharmaceutical Technology Department, Faculty of Pharmacy, International Islamic University, 25200, Kuantan, Pahang, Malaysia.

出版信息

Comput Biol Med. 2021 Jun;133:104412. doi: 10.1016/j.compbiomed.2021.104412. Epub 2021 Apr 18.

DOI:10.1016/j.compbiomed.2021.104412
PMID:33934066
Abstract

Campylobacter jejuni, gram-negative bacteria, is an infectious agent of foodborne disease-causing bloody diarrhea, abdominal pain, fever, Guillain-Barré syndrome (GBS) and Miller Fisher syndrome in humans. Campylobacter spp. with multidrug resistance to fluoroquinolones, tetracycline, and erythromycin are reported. Hence, an effective vaccine candidate would provide long-term immunity against C. jejuni infections. Thus, we used a subtractive proteomics pipeline to prioritize essential proteins, which impart a critical role in virulence, replication and survival. Five proteins, i.e. Single-stranded DNA-binding protein, UPF0324 membrane protein Cj0999c, DNA translocase FtsK, 50S ribosomal protein L22, and 50S ribosomal protein L1 were identified as virulent proteins and selected for vaccine designing. We reported that the multi-epitopes subunit vaccine based on CTL, HTL and B-cell epitopes combination possess strong antigenic properties and associates no allergenic reaction. Further investigation revealed that the vaccine interacts with the immune receptor (TLR-4) and triggered the release of primary and secondary immune factors. Moreover, the CAI and GC contents obtained through codon optimization were reported to be 0.93 and 53% that confirmed a high expression in the selected vector. The vaccine designed in this study needs further scientific consensus and will aid in managing C. jejuni infections.

摘要

空肠弯曲菌,革兰氏阴性菌,是食源性疾病的病原体,可导致人类血性腹泻、腹痛、发热、格林-巴利综合征(GBS)和米勒-费舍尔综合征。已报道弯曲菌属对氟喹诺酮类、四环素和红霉素具有多药耐药性。因此,有效的疫苗候选物将提供针对空肠弯曲菌感染的长期免疫力。因此,我们使用了一种消减蛋白质组学管道来优先考虑在毒力、复制和存活中起关键作用的必需蛋白质。鉴定出 5 种蛋白质,即单链 DNA 结合蛋白、UPF0324 膜蛋白 Cj0999c、DNA 转位酶 FtsK、50S 核糖体蛋白 L22 和 50S 核糖体蛋白 L1,作为毒力蛋白,并选择用于疫苗设计。我们报告了基于 CTL、HTL 和 B 细胞表位组合的多表位亚单位疫苗具有很强的抗原性,并且不引起过敏反应。进一步的研究表明,该疫苗与免疫受体(TLR-4)相互作用,触发了初级和次级免疫因子的释放。此外,通过密码子优化获得的 CAI 和 GC 含量分别为 0.93 和 53%,证实了所选载体中的高表达。本研究设计的疫苗需要进一步的科学共识,并将有助于管理空肠弯曲菌感染。

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