School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar 751024, Odisha, India.
KIIT-Technology Business Incubator (KIIT-TBI), Kalinga Institute of Industrial Technology (KIIT), Deemed to be University, Bhubaneswar 751024, Odisha, India.
J Immunol Methods. 2022 Sep;508:113325. doi: 10.1016/j.jim.2022.113325. Epub 2022 Jul 28.
Acinetobacter baumannii, a prominent pathogen responsible for chronic infections in the blood, urinary tract, and lungs, has a high mortality due to its virulence and limited preventive methods. The present study aims to characterize the pilus assembly protein of A. baumannii to offer leads for epitope-based vaccine development. FilF is the putative pilus assembly protein that reportedly plays a supreme character in the virulence of this WHO-listed ESKAPE bacterium. Implementing various bioinformatics tools, led to the recognition of many antigenic B and T cell epitopes. Most promising B and T-cell epitopes were selected based on their binding efficiency with commonly occurring MHC alleles. Finally, we stepped down to fourteen protective antigenic peptides. These epitopes were also revealed to be non-allergenic and non-toxic. As a result, a vaccine chimera was created by linking these epitopes with appropriate linkers and adjuvant such as β-defensins. Furthermore, homology modeling and validation were carried out, with the modeled structure being employed for molecular docking with the immunological receptor (TLR-4) found on lymphocyte cells. As a result of the molecular dynamics simulation, the interaction between human TLR-4 and the multi-epitope vaccine sequence was stable. Finally, in silico cloning and immune simulation were carried out to see the efficacy of the construct vaccine. This is the first study targeting the pilus assembly protein from A. baumannii to identify novel epitopes that hold potential for further experimental design of multi-peptide vaccine construct against the pathogen.
鲍曼不动杆菌是一种重要的病原体，可导致血液、尿路和肺部的慢性感染，由于其毒力和有限的预防方法，死亡率很高。本研究旨在对鲍曼不动杆菌的菌毛组装蛋白进行特征分析，为基于表位的疫苗开发提供线索。FilF 是一种假定的菌毛组装蛋白，据报道在该世卫组织列出的 ESKAPE 细菌的毒力中起着至关重要的作用。通过使用各种生物信息学工具，识别出许多抗原 B 和 T 细胞表位。根据与常见 MHC 等位基因的结合效率，选择了最有前途的 B 和 T 细胞表位。最后，我们减少到 14 个保护性抗原肽。这些表位也被证明是非变应原性和非毒性的。因此，通过将这些表位与适当的接头和佐剂（如β-防御素）连接，构建了疫苗嵌合体。此外，还进行了同源建模和验证，将建模结构用于与淋巴细胞上发现的免疫受体（TLR-4）进行分子对接。分子动力学模拟的结果表明，人 TLR-4 与多表位疫苗序列之间的相互作用是稳定的。最后，进行了计算机模拟克隆和免疫模拟，以观察构建疫苗的功效。这是首次针对鲍曼不动杆菌菌毛组装蛋白进行的研究，旨在鉴定新的表位，为进一步设计针对该病原体的多肽疫苗构建体提供实验依据。
