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开发针对心内膜炎相关病原体的通用多表位疫苗的泛疫苗组学策略。

Pan-vaccinomics strategy for developing a universal multi-epitope vaccine against endocarditis-related pathogens.

作者信息

Chao Peng, Zhang Xueqin, Zhang Lei, Ma Wei, Wang Dong, Yang Aiping, Chen Xiaoyang

机构信息

Department of Cardiovascular Disease, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.

Department of Nephropathy Disease, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.

出版信息

Front Immunol. 2025 Apr 11;16:1524128. doi: 10.3389/fimmu.2025.1524128. eCollection 2025.

Abstract

INTRODUCTION

Endocarditis is a life-threatening infection of the heart valves, frequently caused by pathogenic bacteria. The growth of multidrug-resistant bacteria necessitates the development of innovative therapeutic techniques, such as vaccines.

METHODS

The current study employed core proteome analysis and a computational-based reverse vaccinology approach across multiple bacterial pathogens associated with endocarditis to identify prospective universal vaccine candidates. The core proteome analysis contained 121 highly pathogenic strains from ten distinct pathogens (, , , , , , , , , and ). The core proteome was subjected to a subtractive proteomics methodology.

RESULTS

Three proteins that were virulent, non-homologous, antigenic, and non-allergenic have been identified as prospective candidates for vaccine development: 30S ribosomal protein S13, 50S ribosomal protein L6, and UMP Kinase. B and T cell epitopes were predicted from vaccine candidate proteins using a range of immune-informatics methods. An in silico vaccine was created by using meticulously chosen epitopes-seven Cytotoxic T lymphocyte (CTL), seven Linear B lymphocyte (LBL), and three Helper T lymphocyte (HTL) epitopes-and subsequently aligning them with the major histocompatibility complex (MHC) molecules (MHC I & MHC II) and human TLR4. A Cholera toxin subunit B (CTB) adjuvant was added to the vaccine to enhance the immunological response. The molecular interactions and binding affinity of the vaccine with TLR4 and MHC molecules were analyzed using molecular dynamics (MD) simulations and molecular docking. To ensure optimal vaccine protein expression, the vaccine was cloned and reverse-translated in .

DISCUSSION

This methodology tackles the difficulties presented by the diversity of pathogens and antibiotic resistance, providing a strategic option for developing efficient and durable vaccines against infections associated with endocarditis.

摘要

引言

心内膜炎是一种危及生命的心脏瓣膜感染,通常由致病细菌引起。多重耐药细菌的出现使得开发创新治疗技术(如疫苗)成为必要。

方法

本研究采用核心蛋白质组分析和基于计算的反向疫苗学方法,对多种与心内膜炎相关的细菌病原体进行研究,以确定潜在的通用疫苗候选物。核心蛋白质组分析包含来自十种不同病原体(、、、、、、、、和)的121株高致病性菌株。对核心蛋白质组采用了消减蛋白质组学方法。

结果

已鉴定出三种具有毒性、非同源、抗原性且无致敏性的蛋白质作为疫苗开发的潜在候选物:30S核糖体蛋白S13、50S核糖体蛋白L6和UMP激酶。使用一系列免疫信息学方法从疫苗候选蛋白中预测B细胞和T细胞表位。通过精心挑选表位——七个细胞毒性T淋巴细胞(CTL)表位、七个线性B淋巴细胞(LBL)表位和三个辅助性T淋巴细胞(HTL)表位——创建了一种虚拟疫苗,随后将它们与主要组织相容性复合体(MHC)分子(MHC I和MHC II)以及人类TLR4进行比对。向疫苗中添加霍乱毒素B亚基(CTB)佐剂以增强免疫反应。使用分子动力学(MD)模拟和分子对接分析疫苗与TLR4和MHC分子的分子相互作用及结合亲和力。为确保疫苗蛋白的最佳表达,将疫苗在中进行克隆和反向翻译。

讨论

该方法解决了病原体多样性和抗生素耐药性带来的难题,为开发针对心内膜炎相关感染的高效持久疫苗提供了一种战略选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da1/12021834/f9c94b7a3794/fimmu-16-1524128-g001.jpg

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