A wide proteome analysis to engineer an efficient epitope based vaccine against Salmonella Typhi: An immunoinformatic study

IF 2.2 4区医学 Q3 IMMUNOLOGY

Human Immunology Pub Date : 2026-04-01 Epub Date: 2026-02-11 DOI:10.1016/j.humimm.2026.111684

Mahsa Beiranvand , Nemat Shams , Amin Jaydari , Narges Nazifi , Peyman Khademi

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Abstract

Background

Typhoid fever, a potentially fatal disease caused by Salmonella enterica serovar Typhi, requires effective vaccines. This study aimed to design a recombinant subunit vaccine using the most immunogenic proteins from the Salmonella Typhi proteome.

Methods

Initially, the most antigenic proteins were selected to predict linear T-cell, B-cell, and IFN-γ epitopes. A recombinant construct incorporating these epitopes, peptide linkers, and a molecular adjuvant was designed. Comprehensive evaluation assessed physicochemical properties, solubility, secondary/tertiary structure, antigenicity, and immune stimulation potential. Molecular docking and dynamics simulations investigated binding to the TLR4/MD2 receptor complex.

Results

Seven proteins from 4322 were chosen for epitope prediction, yielding a 655-amino acid construct. Physicochemical analysis showed 40.31 % hydrophobic amino acids, an aliphatic index of 53.66, GRAVY index of −0.712, and instability index of 22.34. Structural composition was 53.53 % alpha-helix, 8.85 % extended strand, and 40.61 % random coil. Immune simulations demonstrated significant enhancement of primary/secondary humoral and cellular immune responses. The vaccine construct effectively bound the TLR4/MD2 receptor via significant hydrogen bonding (affinity: −1019.1 kcal/mol). Molecular dynamics simulations confirmed the stability of this interaction over 200 ns, demonstrating that both the vaccine candidate and receptor remained structurally stable throughout the simulation period.

Conclusion

Typhoid vaccine candidate shows immunogenic properties, robust immune responses and stable TLR4/MD2 receptor binding.

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一个广泛的蛋白质组分析来设计一个有效的基于表位的伤寒沙门氏菌疫苗：一项免疫信息学研究。

背景：伤寒是一种由伤寒沙门氏菌引起的潜在致命疾病，需要有效的疫苗。本研究旨在利用伤寒沙门氏菌蛋白组中免疫原性最强的蛋白设计重组亚单位疫苗。方法：首先，选择最具抗原性的蛋白来预测线性t细胞、b细胞和IFN-γ表位。设计了包含这些表位、肽连接体和分子佐剂的重组结构。综合评价评估了理化性质、溶解度、二级/三级结构、抗原性和免疫刺激潜力。分子对接和动力学模拟研究了与TLR4/MD2受体复合物的结合。结果：从4322中选择7个蛋白进行表位预测，得到655个氨基酸的结构。理化分析表明，疏水氨基酸占总氨基酸的40.31%，脂肪族指数为53.66，肉汁指数为-0.712，不稳定性指数为22.34。结构组成为53.53%的螺旋体，8.85%的延伸链，40.61%的随机线圈。免疫模拟显示了原发性/继发性体液和细胞免疫反应的显著增强。该疫苗结构通过显著的氢键有效结合TLR4/MD2受体（亲和力：-1019.1 kcal/mol）。分子动力学模拟证实了这种相互作用在200 ns内的稳定性，表明候选疫苗和受体在整个模拟期间都保持结构稳定。结论：伤寒候选疫苗具有免疫原性，免疫应答强，TLR4/MD2受体结合稳定。

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

Human Immunology 医学-免疫学

CiteScore

5.40

自引率

7.40%

发文量

107

审稿时长

12 days

期刊介绍： The journal''s scope includes understanding the genetic and functional mechanisms that distinguish human individuals in their immune responses to allografts, pregnancy, infections or vaccines as well as the immune responses that lead to autoimmunity, allergy or drug hypersensitivity. It also includes examining the distribution of the genes controlling these responses in populations. Research areas include: Studies of the genetics, genomics, polymorphism, evolution, and population distribution of immune-related genes Studies of the expression, structure and function of the products of immune-related genes Immunogenetics of susceptibility to infectious and autoimmune disease, and allergy The role of the immune-related genes in hematopoietic stem cell, solid organ, and vascularized composite allograft transplant Histocompatibility studies including alloantibodies, epitope definition, and T cell alloreactivity Studies of immunologic tolerance and pregnancy T cell, B cell, NK and regulatory cell functions, particularly related to subjects within the journal''s scope Pharmacogenomics and vaccine development in the context of immune-related genes Human Immunology considers immune-related genes to include those encoding classical and non-classical HLA, KIR, MIC, minor histocompatibility antigens (mHAg), immunoglobulins, TCR, BCR, proteins involved in antigen processing and presentation, complement, Fc receptors, chemokines and cytokines. Other immune-related genes may be considered. Human Immunology is also interested in bioinformatics of immune-related genes and organizational topics impacting laboratory processes, organ allocation, clinical strategies, and registries related to autoimmunity and transplantation.