沙门氏菌亚种。enterica(SE)在发达国家和发展中国家都面临着重大的全球卫生挑战。目前的SE疫苗有局限性,针对特定菌株,并在成人中表现出中等疗效,同时也不适合幼儿,并且在疾病流行的收入水平较低的地区通常负担不起。为了应对这些挑战,这项研究采用了一种整合核心蛋白质组学的计算方法,消减蛋白质组学,和免疫信息学来开发通用的SE疫苗并确定潜在的药物靶标。对185个SE菌株的核心蛋白质组的分析揭示了1964个保守的蛋白质。消减蛋白质组学将9种蛋白质鉴定为潜在的疫苗候选物,将41种蛋白质鉴定为新的药物靶标。使用基于反向疫苗学的免疫信息学,设计了四种基于多表位的亚单位疫苗构建体(MESVC),旨在刺激细胞毒性T淋巴细胞,辅助性T淋巴细胞,和线性B淋巴细胞反应。这些构建体进行了抗原性的全面评估,免疫原性,毒性,亲水性,和物理化学性质。预测建模,精致,并进行验证以确定SE-MESVC的二级和三级结构,其次是与MHC-I的对接研究,MHC-II,和TLR4受体。分子对接评估显示与所有三种受体的良好结合,SE-MESVC-4表现出最有希望的结合能。分子动力学模拟证实了SE-MESVC-4与TLR4/MD2复合物的结合亲和力和稳定性。此外,密码子优化和计算机克隆验证了SE-MESVC-4在大肠杆菌中的有效翻译和成功表达(E.大肠杆菌)str.K12随后的计算机模拟免疫模拟评估了SE-MESVC-4在触发有效免疫应答中的功效。这些结果表明,SE-MESVC-4可以诱导体液和细胞免疫反应,使其成为有效SE疫苗的潜在候选者。然而,需要进一步的实验研究来验证SE-MESVC-4的免疫原性和功效,使我们更接近有效对抗SE感染.
Salmonella subsp. enterica (SE) presents a significant global health challenge in both developed and developing countries. Current SE vaccines have limitations, targeting specific strains and demonstrating moderate efficacy in adults, while also being unsuitable for young children and often unaffordable in regions with lower income levels where the disease is prevalent. To address these challenges, this study employed a computational approach integrating core proteomics, subtractive proteomics, and immunoinformatics to develop a universal SE vaccine and identify potential drug targets. Analysis of the core proteome of 185 SE strains revealed 1964 conserved proteins. Subtractive proteomics identified 9 proteins as potential vaccine candidates and 41 as novel drug targets. Using reverse vaccinology-based immunoinformatics, four multi-epitope-based subunit vaccine constructs (MESVCs) were designed, aiming to stimulate cytotoxic T lymphocyte, helper T lymphocyte, and linear B lymphocyte responses. These constructs underwent comprehensive evaluations for antigenicity, immunogenicity, toxicity, hydropathicity, and physicochemical properties. Predictive modeling, refinement, and validation were conducted to determine the secondary and tertiary structures of the SE-MESVCs, followed by docking studies with MHC-I, MHC-II, and TLR4 receptors. Molecular docking assessments showed favorable binding with all three receptors, with SE-MESVC-4 exhibiting the most promising binding energy. Molecular dynamics simulations confirmed the binding affinity and stability of SE-MESVC-4 with the TLR4/MD2 complex. Additionally, codon optimization and in silico cloning verified the efficient translation and successful expression of SE-MESVC-4 in Escherichia coli (E. coli) str. K12. Subsequent in silico immune simulation evaluated the efficacy of SE-MESVC-4 in triggering an effective immune response. These results suggest that SE-MESVC-4 may induce both humoral and cellular immune responses, making it a potential candidate for an effective SE vaccine. However, further experimental investigations are necessary to validate the immunogenicity and efficacy of SE-MESVC-4, bringing us closer to effectively combating SE infections.