Several vaccine candidates have been introduced for immunization against Pseudomonas aeruginosa strains. Despite extensive efforts in recent decades, there is no accurate immunogenic candidate against this pathogen in the market yet. Due to the rapid increase in several drug-resistant strains, P. aeruginosa has caused various health concerns worldwide. It encodes many specific virulence features, which can be used as an appropriate vaccine candidate. The primary stage of the pathogenesis of P. aeruginosa is the expression of many dynamic adhesive molecules, such as type IV pili (T4P), which acts as a principal colonization factor. It has been confirmed that three different subtypes of T4P, including type IVa (T4aP), type IVb (T4bP) and tight adherence (Tad) pili are expressed by P. aeruginosa. The IVa fimbriae type is almost the main cause of challenges to design an effective pili based-immunotherapy method. Nevertheless, in terms of heterogeneity, variability and hidden conserved binding site of T4aP, this attitude has been remained controversial and there is no permitted human study based on IVa pilin commercially. The engineered synthetic peptide-based vaccines are highly talented to mimic the target. In this research, for the first time, some dominant immunogenic features of the Flp protein, such as both B- and T-cell-associated epitopes, presence of IgE-associated epitopes, solvent-accessible surface area were evaluated by analytical immunoinformatics methods. In addition, we designed the engineered Flp pilin as an effective immunogenic substance against several clinically important P. aeruginosa strains. Moreover, by practical active immunization approaches, the humoral and cellular immune response against the extremely conserved region of the engineered synthetic Flp (EFlp) formulated in Montanide ISA 266 compared to the control group. The results of active immunization against EFlp significantly signified that EFlp-Montanide ISA 266 (EFLP-M) strongly could induce both humoral and cellular immune responses. We concluded that Flp pilin has therapeutic potential against numerous clinically significant P. aeruginosa strains and can be served as a novel immunogen for further investigations for development of effective immunotherapy methods against P. aeruginosa as a dexterous pathogen.

已经引入了几种候选疫苗来针对铜绿假单胞菌菌株进行免疫。尽管近几十年来付出了巨大的努力，但是市场上还没有针对这种病原体的准确的免疫原性候选物。由于几种抗药性菌株的迅速增加，铜绿假单胞菌已引起全球范围内的各种健康问题。它编码许多特定的毒力特征，可用作合适的疫苗候选物。铜绿假单胞菌发病机理的初级阶段是许多动态黏附分子的表达，例如IV型菌毛（T4P），它是主要的定居因子。业已证实，铜绿假单胞菌可表达三种不同的T4P亚型，包括IVa型（T4aP），IVb型（T4bP）和紧密粘附（Tad）菌毛。。IVa菌毛类型几乎是设计有效的基于菌毛的免疫治疗方法所面临挑战的主要原因。然而，就T4aP的异质性，变异性和隐藏的保守结合位点而言，这种态度一直存在争议，目前尚无商业上基于IVa菌毛素的人类研究。工程合成的基于肽的疫苗非常有能力模仿靶标。在这项研究中，首次通过分析免疫信息学方法评估了Flp蛋白的一些主要免疫原性特征，例如B细胞和T细胞相关表位，IgE相关表位的存在，溶剂可及的表面积。此外，我们将工程改造的Flp菌毛素设计为可有效抵抗几种临床上重要的铜绿假单胞菌的免疫原性物质。株。此外，与对照组相比，通过实用的主动免疫方法，针对Montanide ISA 266中配制的工程合成Flp（EFlp）极其保守区域的体液和细胞免疫反应。针对EFlp的主动免疫结果显着表明EFlp-Montanide ISA 266（EFLP-M）可以强烈诱导体液和细胞免疫反应。我们得出的结论是，Flp菌毛素对许多具有临床意义的铜绿假单胞菌菌株具有治疗潜力，可以用作新型免疫原，以进一步研究开发针对铜绿假单胞菌作为灵巧病原体的有效免疫治疗方法。