Hasan Ahmad, Alonazi Wadi B, Ibrahim Muhammad, Bin Li
State Key Laboratory of Rice Biology and Breeding, Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou 310058, China.
Health Administration Department, College of Business Administration, King Saud University, Riyadh 11421, Saudi Arabia.
Microorganisms. 2024 Jun 22;12(7):1270. doi: 10.3390/microorganisms12071270.
is a Gram-negative and non-motile bacterium typically transmitted to humans through direct contact with the saliva of infected animals, primarily through biting, scratches, or licks on fractured skin. The absence of a confirmed post-exposure treatment of bacterium highlights the imperative for developing an effective vaccine. We intended to determine potential vaccine candidates and paradigm a chimeric vaccine against by accessible public data analysis of the strain by utilizing reverse vaccinology. By subtractive genomics, five outer membranes were prioritized as potential vaccine candidates out of 2590 proteins. Based on the instability index and transmembrane helices, a multidrug transporter protein with locus ID A0A2A2AHJ4 was designated as a potential candidate for vaccine construct. Sixteen immunodominant epitopes were retrieved by utilizing the Immune Epitope Database. The epitope encodes the strong binding affinity, nonallergenic properties, non-toxicity, high antigenicity scores, and high solubility revealing the more appropriate vaccine construct. By utilizing appropriate linkers and adjuvants alongside a suitable adjuvant molecule, the epitopes were integrated into a chimeric vaccine to enhance immunogenicity, successfully eliciting both adaptive and innate immune responses. Moreover, the promising physicochemical features, the binding confirmation of the vaccine to the major innate immune receptor TLR-4, and molecular dynamics simulations of the designed vaccine have revealed the promising potential of the selected candidate. The integration of computational methods and omics data has demonstrated significant advantages in discovering novel vaccine targets and mitigating vaccine failure rates during clinical trials in recent years.
是一种革兰氏阴性且无运动性的细菌,通常通过与受感染动物的唾液直接接触传播给人类,主要是通过咬伤、抓伤或舔舐破损皮肤。缺乏针对该细菌的确诊暴露后治疗方法凸显了开发有效疫苗的紧迫性。我们旨在通过利用反向疫苗学对该菌株进行可获取的公共数据分析,来确定潜在的疫苗候选物并构建针对该细菌的嵌合疫苗。通过消减基因组学,在2590种蛋白质中,五种外膜蛋白被优先列为潜在的疫苗候选物。基于不稳定指数和跨膜螺旋,将基因座ID为A0A2A2AHJ4的一种多药转运蛋白指定为疫苗构建的潜在候选物。通过利用免疫表位数据库检索到16个免疫显性表位。这些表位编码具有强结合亲和力、无过敏特性、无毒性、高抗原性评分和高溶解性,揭示了更合适的疫苗构建体。通过使用合适的接头和佐剂以及合适的佐剂分子,将这些表位整合到嵌合疫苗中以增强免疫原性,成功引发适应性和先天性免疫反应。此外,所设计疫苗具有良好的物理化学特性、与主要先天性免疫受体TLR-4的结合确认以及分子动力学模拟,都揭示了所选候选物的良好潜力。近年来,计算方法和组学数据的整合在发现新型疫苗靶点和降低临床试验中的疫苗失败率方面已显示出显著优势。