Shah Mohibullah, Fatima Rouman, Sarfraz Asifa, Khan Muhammad Umer, Ejaz Hasan, Alam Maqsood, Aziz Shahid, Nishan Umar, Ali Abid, Bari Ahmed, Ojha Suvash Chandra
Department of Biochemistry, Bahauddin Zakariya University, Multan, Pakistan.
Department of Animal Science, Federal University of Ceara, Fortaleza, Brazil.
Front Immunol. 2025 Jul 4;16:1555248. doi: 10.3389/fimmu.2025.1555248. eCollection 2025.
is known to cause a variety of infections, including mild gastroenteritis and severe systemic disease. This bacterium has developed resistance to several antibiotics, including cephalosporins, penicillins, and fluoroquinolones. Despite significant advances in vaccine formulation against , there is no FDA-licensed vaccine available against it. Herein, the subtractive proteomics approach was utilized to determine the potential drug and vaccine targets, and then reverse vaccinology was utilized to formulate effective vaccines against this pathogen. A core proteome was constructed from the available 22 complete genomes of . Screening resulted in 14 non-human homologous, essential, and virulent proteins being identified as drug targets, while 15 were identified as vaccine targets. The predicted vaccine targets were analyzed, and as a result, two proteins met the criteria for epitope prediction. The epitopes were subjected to a screening pipeline to identify epitopes capable of inducing both T- and B-cell-mediated immune responses. Four vaccine constructs were designed using the selected epitopes by adding the appropriate adjuvants and linkers. The chosen T-cell epitopes showed the possibility of covering 99.26% of the global population. The constructs V1, V2, V3, and V4 were top-ranked based on their physicochemical properties and selected for further analysis. These four vaccines were computationally docked with immune receptors TLR4 and TLR5 to evaluate binding affinities, with V2 and V4 displaying the highest binding affinities with TLR4. The MD simulations, NMA, binding free energy, PCA, and DCCM analysis ensured the stability of complexes. Immune simulations predicted a high immunological profile for the V2 and V4 constructs. Furthermore, cloning assured that the proposed vaccines could be efficiently expressed in the (K12) vector. This study provides valuable insights into developing effective vaccines against ; however, the immunogenicity of the designed vaccine requires experimental validation.
已知会引发多种感染，包括轻度肠胃炎和严重的全身性疾病。这种细菌已对多种抗生素产生耐药性，包括头孢菌素、青霉素和氟喹诺酮类。尽管针对[细菌名称]的疫苗研发取得了重大进展，但尚无美国食品药品监督管理局（FDA）批准的针对该细菌的疫苗。在此，采用消减蛋白质组学方法来确定潜在的药物和疫苗靶点，然后利用反向疫苗学来研发针对这种病原体的有效疫苗。从[细菌名称]现有的22个完整基因组构建了一个核心蛋白质组。筛选结果确定了14种非人类同源、必需且有毒的蛋白质作为药物靶点，同时确定了15种作为疫苗靶点。对预测的疫苗靶点进行了分析，结果有两种蛋白质符合表位预测标准。对这些表位进行筛选流程，以鉴定能够诱导T细胞和B细胞介导的免疫反应的表位。通过添加合适的佐剂和连接子，使用选定的表位设计了四种疫苗构建体。所选的T细胞表位显示有可能覆盖全球99.26%的人口。构建体V1、V2、V3和V4根据其物理化学性质排名靠前，并被选作进一步分析。这四种疫苗与免疫受体TLR4和TLR5进行了计算机对接，以评估结合亲和力，其中V2和V4与TLR4显示出最高的结合亲和力。分子动力学模拟、正常模态分析、结合自由能、主成分分析和动态交叉相关矩阵分析确保了复合物的稳定性。免疫模拟预测V2和V4构建体具有高免疫原性。此外，克隆确保了所提出的疫苗能够在[载体名称]（K12）载体中高效表达。本研究为研发针对[细菌名称]的有效疫苗提供了有价值的见解；然而，所设计疫苗的免疫原性需要进行实验验证。
