针对相关慢性肝脏炎症的多表位疫苗候选物的计算机模拟设计与实验验证。{"i":["幽门螺杆菌"]}
{"_":" design and experimental validation of a multi-epitope vaccine candidate against associated chronic liver inflammation.","i":["In silico","Helicobacter hepaticus"]}
摘要(中文译文)
是一种新出现的肠肝病原体，与慢性胃肠道和肝脏炎症性疾病相关。尽管其具有临床意义，但由于抗原变异性、免疫逃逸以及难以诱导持久的细胞免疫，有效的疫苗接种策略仍然缺乏。本研究采用反向疫苗学与实验验证相结合的综合方法，设计针对该病原体的多表位疫苗。基于抗原性、表面暴露性和安全性分析，选取了两种保守的外膜蛋白——BamA和一种有机溶剂耐受蛋白。预测了免疫显性的细胞毒性T细胞和辅助性T细胞表位，对其免疫原性、致敏性和毒性进行了筛选，并组装成一个合理设计的构建体，其中加入人β-防御素-3作为佐剂。进行了结构建模、构象B细胞表位定位、分子对接、分子动力学模拟以及计算机免疫模拟。该构建体在表达系统中进行了重组表达，并通过生物物理、抗菌和免疫学实验进行了评估。该候选疫苗表现出良好的理化性质、结构稳定性以及对Toll样受体2的强结合亲和力。计算机免疫模拟预测其可诱导强烈的Th1偏向性免疫应答并有效形成免疫记忆。重组表达获得了可溶性、单分散的蛋白。功能实验表明该蛋白可显著抑制病原体生长及宿主细胞黏附。免疫原性研究显示其可强烈促进外周血单个核细胞增殖、增强CD4和CD8 T细胞活化、提高Th1细胞因子分泌以及诱导抗原特异性抗体产生。所提出的多表位候选疫苗可诱导协同的固有免疫和适应性免疫应答，并对该病原体表现出有前景的抗菌活性。本研究为基于表位的疫苗开发提供了全面且具有转化意义的框架，并支持对该候选疫苗开展进一步的评价。
Abstract
is an emerging enterohepatic pathogen associated with chronic gastrointestinal and hepatic inflammatory disorders. Despite its clinical relevance, effective vaccination strategies remain unavailable due to antigenic variability, immune evasion, and limited induction of durable cellular immunity. An integrated reverse vaccinology and experimental validation approach was employed to design a multi-epitope vaccine against . Two conserved outer membrane proteins, BamA and an organic solvent tolerance protein, were selected based on antigenicity, surface exposure, and safety profiling. Immunodominant cytotoxic and helper T-cell epitopes were predicted, screened for immunogenicity, allergenicity, and toxicity, and assembled into a rationally designed construct incorporating human β-defensin-3 as an adjuvant. Structural modeling, conformational B-cell epitope mapping, molecular docking, molecular dynamics simulations, and in silico immune simulations were performed. The construct was recombinantly expressed in and evaluated through biophysical, antibacterial, and immunological assays. The vaccine candidate exhibited favorable physicochemical properties, structural stability, and strong binding affinity toward Toll-like receptor 2. In silico immune simulations predicted robust Th1-biased immune responses with effective memory formation. Recombinant expression yielded a soluble, monodisperse protein. Functional assays demonstrated significant inhibition of growth and host cell adhesion. immunogenicity studies revealed strong peripheral blood mononuclear cell proliferation, enhanced CD4 and CD8 T-cell activation, elevated Th1 cytokine secretion, and antigen-specific antibody production. The proposed multi-epitope vaccine candidate induces coordinated innate and adaptive immune responses and exhibits promising antibacterial activity against . This study provides a comprehensive and translational framework for epitope-based vaccine development and supports further evaluation of the candidate vaccine.
如何引用
AMA
Liangliang Weng, Zhang Huijie, Ni Man, Liu Yang, Min Cao. {"_":" design and experimental validation of a multi-epitope vaccine candidate against associated chronic liver inflammation.","i":["In silico","Helicobacter hepaticus"]}. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1799290.
APA
Liangliang Weng, Zhang Huijie, Ni Man, Liu Yang, Min Cao (2026). {"_":" design and experimental validation of a multi-epitope vaccine candidate against associated chronic liver inflammation.","i":["In silico","Helicobacter hepaticus"]}. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1799290
GB/T 7714
Liangliang Weng, Zhang Huijie, Ni Man, Liu Yang, Min Cao. {"_":" design and experimental validation of a multi-epitope vaccine candidate against associated chronic liver inflammation.","i":["In silico","Helicobacter hepaticus"]}[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1799290.
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