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探索囊多糖蛋白以设计多表位亚单位疫苗来对抗肺炎。

Exploring capsule polysaccharide proteins to design multiepitope subunit vaccine to fight against pneumonia.

机构信息

School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to Be University, Bhubaneswar, India.

Kalinga Institute of Dental Sciences, KIIT Deemed to Be University, Bhubaneswar, India.

出版信息

Expert Rev Vaccines. 2022 Apr;21(4):569-587. doi: 10.1080/14760584.2022.2021882. Epub 2022 Jan 4.

Abstract

BACKGROUND

is an emerging human pathogen causing neonatal lung disease, catheter-associated infections, and nosocomial outbreaks with high fatality rates. Capsular polysaccharide (CPS) protein plays a major determinant in virulence and is considered as a promising target for vaccine development.

RESEARCH DESIGN AND METHODS

In this study, we used immunoinformatic approaches to design a multi-peptide vaccine against K. pneumonia. The epitopes were selected through several immune filters, such as antigenicity, conservancy, nontoxicity, non-allergenicity, binding affinity to HLA alleles, overlapping epitopes, and peptides having common epitopes.

RESULTS

Finally, a construct comprising 2 B-Cell, 8 CTL, 2 HTL epitopes, along with adjuvant, linkers was designed. Peptide-HLA interaction analysis showed strong binding of these epitopes with several common HLA molecules. The in silico immune simulation and population coverage analysis of the vaccine showed its potential to evoke strong immune responses.. Further, the interaction between vaccine and immune was evaluated by docking and simulation, revealing high affinity and complex stability. Codon adaptation and in silico cloning revealed higher expression of vaccine in E. coli K12 expression system.

CONCLUSIONS

Conclusively, the findings of the present study suggest that the designed novel multi-epitopic vaccine holds potential for further experimental validation against the pathogen.

摘要

背景

是一种新兴的人类病原体,可导致新生儿肺部疾病、导管相关感染和医院感染暴发,死亡率很高。荚膜多糖(CPS)蛋白是决定其毒力的主要因素,被认为是疫苗开发的有前途的靶点。

研究设计与方法

在这项研究中,我们使用免疫信息学方法设计了一种针对肺炎克雷伯菌的多肽疫苗。通过几种免疫过滤器(如抗原性、保守性、非毒性、非变应原性、与 HLA 等位基因的结合亲和力、重叠表位和具有共同表位的肽)选择表位。

结果

最后,设计了一个包含 2 个 B 细胞、8 个 CTL 和 2 个 HTL 表位的构建体,以及佐剂和接头。肽-HLA 相互作用分析表明,这些表位与几种常见的 HLA 分子具有很强的结合能力。疫苗的免疫模拟和人群覆盖率分析表明,它有潜力引发强烈的免疫反应。此外,通过对接和模拟评估了疫苗与免疫的相互作用,显示出高亲和力和复杂的稳定性。密码子适应和计算机模拟克隆显示,在大肠杆菌 K12 表达系统中,疫苗的表达水平更高。

结论

总之,本研究的结果表明,所设计的新型多表位疫苗具有进一步实验验证针对该病原体的潜力。

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