Design and in silico evaluation of a novel chimeric protein vaccine candidate against Salmonella Typhi

IF 1.9 4区生物学 Q4 BIOCHEMICAL RESEARCH METHODS

Journal of microbiological methods Pub Date : 2025-09-18 DOI:10.1016/j.mimet.2025.107268

Mohsen Bidar Ajerloo , Abbas Hajizade , Shahram Nazarian , Kavyan Khalili

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引用次数: 0

Abstract

Typhoid fever, caused by Salmonella enteritidis serovar Typhi (S. Typhi), remains a significant global health challenge, especially in regions with poor sanitation. Despite available vaccines, limitations such as short-term efficacy and variable immune responses necessitate novel strategies. Here, we designed a multi-protein chimeric protein vaccine targeting S. Typhi by integrating three key antigens: SteD (an immune-evasion transmembrane effector) (whole protein), flagellin (D1 domain), and STIV (Salmonella Typhi invasion protein) (whole protein). Proteins were linked via rigid EAAAK linkers to enhance stability. The construct exhibited high antigenicity (VaxiJen score:0. 9228) and favorable physicochemical properties (ProtParam), with non-allergenic (AlgPred) and non-toxic (ToxinPred) profiles. Structural analysis revealed a stable 3D model (I-TASSER/Phyre2/RaptorX), validated by Ramachandran plot (>90 % favored regions), ProSA z-score of −5.54, and ERRAT. B-cell and T-cell epitopes predicted by IEDB, ABCPred, and Discotope 2.0 demonstrated strong binding to HLA alleles. Molecular docking confirmed robust interactions with TLR-4 (PDB:2Z63) and TLR-5 (PDB:3V44), while 100-ns MD simulations (NAMD/VMD) affirmed complex stability (low RMSD/RMSF). Immune simulations (C-ImmSim) predicted potent humoral and cellular responses, including elevated IgG/IgM and Th1/Th2 cytokines. This in silico study proposes a promising vaccine candidate with high theoretical immunogenicity and structural integrity, warranting further in vitro and in vivo validation.

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一种新型伤寒沙门氏菌嵌合蛋白候选疫苗的设计与计算机评价。

伤寒由肠炎沙门氏菌血清型伤寒沙门氏菌（S. Typhi）引起，仍然是一个重大的全球卫生挑战，特别是在卫生条件差的地区。尽管有现有的疫苗，但诸如短期疗效和可变的免疫反应等限制需要新的策略。本研究通过整合三种关键抗原：免疫逃逸跨膜效应蛋白SteD（全蛋白）、鞭毛蛋白（D1结构域）和伤寒沙门氏菌侵袭蛋白STIV（全蛋白），设计了一种针对伤寒沙门氏菌的多蛋白嵌合蛋白疫苗。蛋白质通过刚性EAAAK连接体连接以增强稳定性。该构建体具有较高的抗原性（VaxiJen评分：0）。9228)和良好的物理化学性质（ProtParam），具有非过敏性（AlgPred）和无毒（ToxinPred）谱。结构分析显示稳定的3D模型（I-TASSER/Phyre2/RaptorX），经Ramachandran图（bbb90 %有利区域）验证，ProSA z-score为-5.54，ERRAT。通过IEDB、ABCPred和Discotope 2.0预测的b细胞和t细胞表位显示出与HLA等位基因的强结合。分子对接证实了与TLR-4 （PDB:2Z63）和TLR-5 （PDB:3V44）的强相互作用，而100-ns MD模拟（NAMD/VMD）证实了复合物的稳定性（低RMSD/RMSF）。免疫模拟（C-ImmSim）预测了强有力的体液和细胞反应，包括升高的IgG/IgM和Th1/Th2细胞因子。这项计算机研究提出了一种有希望的候选疫苗，具有很高的理论免疫原性和结构完整性，需要进一步的体外和体内验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of microbiological methods 生物-生化研究方法

CiteScore

4.30

自引率

4.50%

发文量

151

审稿时长

29 days

期刊介绍： The Journal of Microbiological Methods publishes scholarly and original articles, notes and review articles. These articles must include novel and/or state-of-the-art methods, or significant improvements to existing methods. Novel and innovative applications of current methods that are validated and useful will also be published. JMM strives for scholarship, innovation and excellence. This demands scientific rigour, the best available methods and technologies, correctly replicated experiments/tests, the inclusion of proper controls, calibrations, and the correct statistical analysis. The presentation of the data must support the interpretation of the method/approach. All aspects of microbiology are covered, except virology. These include agricultural microbiology, applied and environmental microbiology, bioassays, bioinformatics, biotechnology, biochemical microbiology, clinical microbiology, diagnostics, food monitoring and quality control microbiology, microbial genetics and genomics, geomicrobiology, microbiome methods regardless of habitat, high through-put sequencing methods and analysis, microbial pathogenesis and host responses, metabolomics, metagenomics, metaproteomics, microbial ecology and diversity, microbial physiology, microbial ultra-structure, microscopic and imaging methods, molecular microbiology, mycology, novel mathematical microbiology and modelling, parasitology, plant-microbe interactions, protein markers/profiles, proteomics, pyrosequencing, public health microbiology, radioisotopes applied to microbiology, robotics applied to microbiological methods,rumen microbiology, microbiological methods for space missions and extreme environments, sampling methods and samplers, soil and sediment microbiology, transcriptomics, veterinary microbiology, sero-diagnostics and typing/identification.