Habiba Tooba Ume, Hussain Zahid, Asghar Fatima, Nawaz Wajeeha
Dr. Ikram-ul-Haq Institute of Industrial Biotechnology (IIIB), Government College University, Lahore, Pakistan.
BMC Microbiol. 2025 Aug 23;25(1):542. doi: 10.1186/s12866-025-04124-y.
BACKGROUND: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a leading cause of salmonellosis, gastroenteritis, sepsis, and reactive arthritis. Transmission primarily occurs through contaminated water, eggs, meat, and dairy products. The disease disproportionately affects developing nations, where young children, the elderly, and immunocompromised individuals face high risks of severe morbidity and mortality. Its ability to evade host immune defenses and acquire multidrug resistance (MDR) exacerbates global public health challenges. Currently, no licensed human vaccine is available, underscoring the urgent need for targeted vaccine development. METHODS: This study utilized a reverse vaccinology approach and in silico strategies to identify highly immunogenic membrane proteins as potential vaccine candidates. The complete proteome of S. Typhimurium was screened for membrane-associated candidates using the SOSUI server. Antigenicity was evaluated using VaxiJen v2.0 (threshold ≥ 0.9), and allergenicity was assessed using AllerTOP v1.1. To ensure vaccine safety, homologous proteins were excluded based on PSI-BLAST analysis against the human proteome, and toxicity was predicted using ToxinPred. The immunogenic potential was further evaluated through C-ImmSim immune simulation software. B-cell and T-cell epitopes were predicted using ABCpred and the Immune Epitope Database (IEDB). Physicochemical characteristics were analyzed with ProtParam and TMHMM 2.0. Finally, BLASTp analysis was used to confirm the conservation of the selected proteins across MDR clinical isolates. RESULTS: Nine membrane proteins were prioritized based on strong antigenicity, non-allergenicity, non-toxicity, favorable epitope profiles, and physicochemical stability. All proteins were highly conserved in MDR isolates, supporting their utility for broad-spectrum vaccine development. CONCLUSION: These targets show promising potential for developing a broadly protective multi-epitope vaccine against S. Typhimurium. However, in vitro and in vivo experimental validation is essential to confirm their immunogenicity and protective efficacy.
背景：肠炎沙门氏菌鼠伤寒血清型（鼠伤寒沙门氏菌）是沙门氏菌病、肠胃炎、败血症和反应性关节炎的主要病因。传播主要通过受污染的水、鸡蛋、肉类和乳制品发生。该疾病对发展中国家的影响尤为严重，在这些国家，幼儿、老年人和免疫功能低下的个体面临着严重发病和死亡的高风险。其逃避宿主免疫防御并获得多重耐药性（MDR）的能力加剧了全球公共卫生挑战。目前，尚无获得许可的人用疫苗，这凸显了针对性疫苗开发的迫切需求。 方法：本研究采用反向疫苗学方法和计算机策略来鉴定高免疫原性膜蛋白作为潜在的疫苗候选物。使用SOSUI服务器对鼠伤寒沙门氏菌的完整蛋白质组进行膜相关候选物筛选。使用VaxiJen v2.0（阈值≥0.9）评估抗原性，使用AllerTOP v1.1评估致敏性。为确保疫苗安全性，基于针对人类蛋白质组的PSI-BLAST分析排除同源蛋白，并使用ToxinPred预测毒性。通过C-ImmSim免疫模拟软件进一步评估免疫原性潜力。使用ABCpred和免疫表位数据库（IEDB）预测B细胞和T细胞表位。使用ProtParam和TMHMM 2.0分析理化特性。最后，使用BLASTp分析来确认所选蛋白质在多重耐药临床分离株中的保守性。 结果：基于强抗原性、无致敏性、无毒性、良好的表位谱和理化稳定性，对九种膜蛋白进行了优先排序。所有蛋白质在多重耐药分离株中高度保守，支持它们在广谱疫苗开发中的效用。 结论：这些靶点在开发针对鼠伤寒沙门氏菌的广泛保护性多表位疫苗方面显示出有前景的潜力。然而，体外和体内实验验证对于确认它们的免疫原性和保护效力至关重要。
Microorganisms. 2024-7-2
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