Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Department of Pharmacology, Institute of Pharmaceutical Sciences, Jinnah Sindh Medical University, Karachi, Pakistan.
J Biomol Struct Dyn. 2024 Oct;42(16):8559-8573. doi: 10.1080/07391102.2023.2246587. Epub 2023 Aug 14.
A prevalent food-borne pathogen, is responsible for gastrointestinal and systemic infections globally. vaccines are the most effective, however, producing a broad-spectrum vaccine remains challenging due to many serotypes. Efforts are urgently required to develop a novel vaccine candidate that can tackle all strains because of their high resistance to multiple kinds of antibiotics (particularly the XDR H58 strain). In this work, we used a computational pangenome-based vaccine design technique on all available ( = 119) reference genomes and identified one TonB-dependent siderophore receptor (WP_001034967.1) as highly conserved and prospective vaccine candidates from the predicted core genome ( = 3,351). The applied pan-proteomics and Immunoinformatic approaches help in the identification of four epitopes that may trigger adequate host body immune responses. Furthermore, the proposed vaccine ensemble demonstrates a stable binding conformation with the examined immunological receptor (HLAs and TRL2/4) and has large interaction energy determined molecular docking and molecular dynamics simulation techniques. Eventually, an expression vector for the K12 strain was constructed from the vaccine sequence. Additional analysis revealed that the vaccine may help to elicit strong immune responses for typhoid infections, however, experimental analysis is required to verify the vaccine's effectiveness based on these results. Moreover, the applied computer-assisted vaccine design may considerably decrease vaccine development costs and speed up the process. The study's findings are intriguing, but they must be evaluated in the experimental labs to confirm the developed vaccine's biological efficiency against XDR .Communicated by Ramaswamy H. Sarma.
一种流行的食源性病原体,是全球胃肠道和全身感染的罪魁祸首。疫苗是最有效的方法,然而,由于有许多血清型,生产广谱疫苗仍然具有挑战性。由于其对多种抗生素(特别是 XDR H58 株)具有很高的耐药性,迫切需要开发一种新型疫苗候选物来应对所有菌株。在这项工作中,我们使用了基于全基因组的计算疫苗设计技术,对所有可用的(= 119)参考基因组进行了分析,并从预测的核心基因组(= 3351)中鉴定出一个 TonB 依赖性铁载体受体(WP_001034967.1)作为高度保守和有前途的疫苗候选物。应用泛蛋白组学和免疫信息学方法有助于鉴定四个可能引发宿主产生足够免疫反应的表位。此外,所提出的疫苗组合与所研究的免疫受体(HLAs 和 TRL2/4)表现出稳定的结合构象,并通过分子对接和分子动力学模拟技术确定了较大的相互作用能。最终,从 K12 株的疫苗序列构建了一个表达载体。进一步的分析表明,该疫苗可能有助于引发伤寒感染的强烈免疫反应,但需要进行实验分析以根据这些结果验证疫苗的有效性。此外,应用计算机辅助疫苗设计可以大大降低疫苗开发成本并加快进程。该研究的结果令人感兴趣,但必须在实验实验室中进行评估,以确认针对 XDR 的开发疫苗的生物学效率。由 Ramaswamy H. Sarma 传达。