Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Department of Pharmacy, Al-Mustaqbal University College, Hillah, Babylon 51001, Iraq.
Int J Environ Res Public Health. 2022 Aug 29;19(17):10742. doi: 10.3390/ijerph191710742.
The misuse of antibiotics in our daily lives has led to the emergence of antimicrobial resistance. As a result, many antibiotics are becoming ineffective. This phenomenon is linked with high rates of mortality and morbidity. Therefore, new approaches are required to address this major health issue. is a Gram-negative, rod-shaped bacterium which normally resides in the oral and vaginal cavities. It is an emerging bacterial pathogen which is developing new antibiotic-resistance mechanisms. No approved vaccine is available against this pathogen, which is a cause for growing concern. In this study, an in silico-based, multi-epitopes vaccine against this pathogen was designed by applying reverse vaccinology and immunoinformatic approaches. Of a total of 2193 predicted proteins, 294 were found to be redundant while 1899 were non-redundant. Among the non-redundant proteins, 6 were predicted to be present in the extracellular region, 12 in the periplasmic region and 23 in the outer-membrane region. Three proteins (trypsin-like peptidase domain-containing protein, sel1 repeat family protein and TrbI/VirB10 family protein) were predicted to be virulent and potential subunit vaccine targets. In the epitopes prediction phase, the three proteins were subjected to B- and T-cell epitope mapping; 19 epitopes were used for vaccine design. The vaccine construct was docked with MHC-I, MHC-II and TLR-4 immune receptors and only the top-ranked complex (based on global energy value) was selected in each case. The selected docked complexes were examined in a molecular dynamic simulation and binding free energies analysis in order to assess their intermolecular stability. It was observed that the vaccine binding mode with receptors was stable and that the system presented stable dynamics. The net binding free energy of complexes was in the range of -300 to -500 kcal/mol, indicating the formation of stable complexes. In conclusion, the data reported herein might help vaccinologists to formulate a chimeric vaccine against the aforementioned target pathogen.
日常生活中抗生素的滥用导致了抗菌药物耐药性的出现。结果,许多抗生素变得无效。这种现象与高死亡率和发病率有关。因此,需要新的方法来解决这一重大健康问题。 是一种革兰氏阴性、杆状细菌,通常存在于口腔和阴道腔中。它是一种新兴的细菌病原体,正在开发新的抗生素耐药机制。针对这种病原体,尚无批准的疫苗,这是一个令人日益关注的问题。在这项研究中,通过应用反向疫苗学和免疫信息学方法,设计了针对这种病原体的基于计算机的多表位疫苗。在总共 2193 个预测蛋白中,发现 294 个是冗余的,而 1899 个是非冗余的。在非冗余蛋白中,有 6 个被预测存在于细胞外区,12 个存在于周质区,23 个存在于外膜区。三种蛋白(胰蛋白酶样肽酶结构域蛋白、sel1 重复家族蛋白和 TrbI/VirB10 家族蛋白)被预测为毒力蛋白和潜在的亚单位疫苗靶点。在表位预测阶段,将这三种蛋白进行 B 细胞和 T 细胞表位作图;使用 19 个表位进行疫苗设计。疫苗构建体与 MHC-I、MHC-II 和 TLR-4 免疫受体对接,在每种情况下,仅选择排名最高的复合物(基于全局能量值)。选择对接复合物进行分子动力学模拟和结合自由能分析,以评估它们的分子间稳定性。结果表明,疫苗与受体的结合模式稳定,系统呈现稳定的动力学。复合物的净结合自由能在-300 到-500 kcal/mol 范围内,表明形成了稳定的复合物。总之,本文报道的数据可能有助于疫苗学家针对上述靶标病原体制定嵌合疫苗。