一种含有多个表位的新型嵌合疫苗,可模拟针对肺炎克雷伯菌的强效免疫激活

IF 2.9 4区 医学 Q3 IMMUNOLOGY BMC Immunology Pub Date : 2024-05-05 DOI:10.1186/s12865-024-00617-z
Morteza Hakimian, Abbas Doosti, Ali Sharifzadeh
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引用次数: 0

摘要

由于抗生素耐药性,克雷伯氏菌属与发病和死亡有关,因此有必要开发一种针对克雷伯氏菌病原体的通用保护性疫苗。核心序列分析从完全测序的克雷伯氏菌基因组中优先选择了非冗余宿主分子和预期脂双层肽。对这些蛋白质进行了提炼,以确定表位,检查其免疫原性、毒性、可溶性以及与 MHC 等位基因的相互作用。表位通过 EAAAK、HEYGAEALERAG 和 GGGS 连接器与 CPG ODN C274 连接,以增强免疫反应。对疫苗的三级结构进行了建模,并与 MHC-I 和 MHC-II 进行了对接。Vaxign 收集的 55 种蛋白质被认为具有显著特征。随后又确定了 23 种具有潜在致病性的蛋白质。在对蛋白质的免疫原性进行检查后,出现了八种疫苗选择。最佳抗原是三种蛋白质:MrkD、铁调节脂膜多肽和 RmpA。这些化合物因其敏感性而被选中。利用肺炎双球菌的结构蛋白序列,分别确定了七个 CTL 表位、七个 HTL 表位和七个 LBL 表位。根据持续 250 纳秒的分子动力学模拟,所产生的免疫与受体有稳定的接触。分子间结合自由能也表明范德华能和静电能占主导地位。总之,这项研究的结果可能有助于科学家们开发出一种新型疫苗来预防肺炎双球菌感染。
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A novel chimeric vaccine containing multiple epitopes for simulating robust immune activation against Klebsiella pneumoniae
Due to antibiotic resistance, the Klebsiella genus is linked to morbidity and death, necessitating the development of a universally protective vaccine against Klebsiella pathogens. Core sequence analysis prioritized non-redundant host molecules and expected lipid bilayer peptides from fully sequenced Klebsiella genomes. These proteins were refined to identify epitopes, examining their immunogenicity, toxicity, solubility, and interaction with MHC alleles. Epitopes were linked to CPG ODN C274 via EAAAK, HEYGAEALERAG, and GGGS linkers to enhance immunological responses. The vaccine’s tertiary structure was modelled and docked with MHC-I and MHC-II. Fifty-five proteins were recognized in the Vaxign collection as having remarkable features. Twenty-three proteins with potential pathogenicity were then identified. Eight options for vaccines emerged after the immunogenicity of proteins was examined. The best antigens were three proteins: MrkD, Iron-regulated lipid membrane polypeptides, and RmpA. These compounds were selected for their sensitivity. The structural protein sequences of K. pneumoniae were utilized to identify seven CTL epitopes, seven HTL epitopes, and seven LBL epitopes, respectively. The produced immunization displayed a stable contact with the receptors, based on molecular dynamic simulations lasting 250 nanoseconds. Intermolecular binding free energies also indicated the dominance of the van der Waals and electrostatic energies. In summary, the results of this study might help scientists develop a novel vaccine to prevent K. pneumoniae infections.
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来源期刊
BMC Immunology
BMC Immunology 医学-免疫学
CiteScore
5.50
自引率
0.00%
发文量
54
审稿时长
1 months
期刊介绍: BMC Immunology is an open access journal publishing original peer-reviewed research articles in molecular, cellular, tissue-level, organismal, functional, and developmental aspects of the immune system as well as clinical studies and animal models of human diseases.
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