Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.
Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.
Infect Genet Evol. 2020 Nov;85:104462. doi: 10.1016/j.meegid.2020.104462. Epub 2020 Jul 16.
Increasing in drug-resistant Pseudomonas aeruginosa and high mortality and morbidity rate have become a health challenge worldwide; therefore, developing the novel therapeutic strategies such as immunogenic vaccine candidate are required. Despite a substantial research effort, the future of immunization against P. aeruginosa due to failure in covering two separate stages of infection, and furthermore, inducing ineffective type of immune response, still remains controversial. In this study, immunoinformatics approach was utilized to design multivalent chimeric vaccine from both stages of infection containing Lectin, HIV TAT peptide, N-terminal fragment of exotoxin A and Epi8 of outer membrane protein F (OprF) with hydrophobic linkers which have a high density of B-cell, T Lymphocytes (HTL), T Lymphocytes (CTL), and IFN-γ epitopes. The physicochemical properties, antigenicity, and allergenicity for designed vaccine were analyzed. 3D model generation and refinement further validation of the final vaccine were followed by computational docking with molecular dynamics analyses that demonstrated high- affinity interaction between vaccine and TLR-4. Finally, designed vaccine was in silico cloned in pET22b. We have expected that the designed vaccine able to elucidate innate, humoral and cellular innate immune responses and control the interaction of P. aeruginosa with host and maybe overcome to P. aeruginosa vaccines drawback.
铜绿假单胞菌耐药性增加以及高死亡率和发病率已成为全球健康挑战；因此，需要开发新的治疗策略，如免疫原性疫苗候选物。尽管进行了大量研究，但由于未能涵盖感染的两个不同阶段，并且诱导无效的免疫反应类型，针对铜绿假单胞菌的免疫接种的未来仍然存在争议。在这项研究中，利用免疫信息学方法从感染的两个阶段设计多价嵌合疫苗，包含凝集素、HIV TAT 肽、外毒素 A 的 N 端片段和外膜蛋白 F（OprF）的 Epi8，带有疏水区连接子，具有高密度的 B 细胞、T 淋巴细胞（HTL）、T 淋巴细胞（CTL）和 IFN-γ 表位。分析了设计疫苗的理化性质、抗原性和变应原性。进一步通过计算对接和分子动力学分析对 3D 模型生成和细化进行了验证，结果表明疫苗与 TLR-4 之间具有高亲和力相互作用。最后，在 pET22b 中对设计的疫苗进行了计算机克隆。我们期望设计的疫苗能够阐明先天、体液和细胞先天免疫反应，并控制铜绿假单胞菌与宿主的相互作用，也许能够克服铜绿假单胞菌疫苗的缺点。
