Jahangiri Abolfazl, Rasooli Iraj, Owlia Parviz, Imani Fooladi Abbas Ali, Salimian Jafar
Department of Biology, Shahed University, Tehran, Iran.
Department of Biology, Shahed University, Tehran-Qom Express Way, Tehran, Iran.
J Microbiol Methods. 2018 Jan;144:79-85. doi: 10.1016/j.mimet.2017.11.008. Epub 2017 Nov 10.
Omp34, also known as Omp34kDa or Omp33-36 is a virulence factor associated with A. baumannii metabolic fitness or its adherence and invasion to human epithelial cells. This protein is also introduced as a specific antigen which could induce strong antibody responses. In the present in silico study, recent vaccine design strategies such as 'antigen minimization' and 'high epitope density' were invoked to design a soluble immunogen with higher antigenicity. As an advantage, the tools employed in the current study are easily available. Exposed peptides in linear B-cell epitopes were predicted and their conservancy and immunogenicity were evaluated. In this regard, constructs were designed by removal of inappropriate regions. Based on the obtained results the external loops (L1-L7) were exclusively considered of which L3, L6 and L7 were the most appropriate of which the most appropriate were in L3>L6>L7 order while L2 was assigned as an inappropriate peptide. The final construct, named Omp34-4, encompasses three copies of L3, two copies of L6 and L7 and one copy of L1, L4 and L5. The designed construct is predicted to be a soluble antigen with enhanced epitope density and antigenicity. Omp34 is present in >1600 strains of A. baumannii with ≥98% identity. So, it could be applicable in diagnostic kits and an immunotherapy choice against A. baumannii. It could be presumed that co-administration of Omp34-4 and a recently designed OmpA-derived antigen could confer sufficient protection against A. baumannii-associated infections. In vitro and in vivo experiments are needed to confirm all these data. The innovative approach could be generalized to vaccine designs focused on OMPs.
外膜蛋白34（Omp34），也被称为Omp34kDa或Omp33 - 36，是一种与鲍曼不动杆菌代谢适应性或其对人上皮细胞的黏附及侵袭相关的毒力因子。这种蛋白也被作为一种能诱导强烈抗体反应的特异性抗原。在本计算机模拟研究中，运用了诸如“抗原最小化”和“高表位密度”等最新疫苗设计策略来设计一种具有更高抗原性的可溶性免疫原。作为一个优势，本研究中使用的工具很容易获得。预测了线性B细胞表位中暴露的肽段，并评估了它们的保守性和免疫原性。在这方面，通过去除不合适的区域来设计构建体。根据所得结果，专门考虑了外部环（L1 - L7），其中L3、L6和L7是最合适的，最合适程度依次为L3 > L6 > L7，而L2被指定为不合适的肽段。最终构建体名为Omp34 - 4，包含三个L3拷贝、两个L6和L7拷贝以及一个L1、L4和L5拷贝。所设计的构建体预计是一种具有增强表位密度和抗原性的可溶性抗原。Omp34存在于超过1600株鲍曼不动杆菌中，同一性≥98%。因此，它可应用于诊断试剂盒以及针对鲍曼不动杆菌的免疫治疗选择。可以推测，联合使用Omp34 - 4和最近设计的OmpA衍生抗原有望为预防鲍曼不动杆菌相关感染提供充分保护。需要进行体外和体内实验来证实所有这些数据。这种创新方法可推广到针对外膜蛋白的疫苗设计中。
