Homology modelling and molecular simulation approach to prediction of B-cell and T-cell epitopes in an OMP25 peptide vaccine against <i>Brucella abortus</i>

The live attenuated vaccine composition against brucellosis poses potential risks to recipient animals. Therefore, we have analysed an <i>in-silico</i> approach to design a novel multi-epitope vaccine peptide to elicit a desirable immune response against <i>Brucella abortus</i> infection. This study designed a peptide vaccine based on outer membrane protein from <i>B. abortus</i>. The selected OMP sequence shows 0.7575 antigenic proteins. We predicted the T-cell epitopes of different lengths. Cluster analysis was performed for 180 epitope peptides, showcasing a total of 19 clusters, constituting 14 clusters as Consensus clusters and 5 as Singleton clusters. We select the top three clusters which has 24 peptides showing antigen property. Selected 24-antigen peptides were docked with MHC classes I and II and selected the top eight peptides based on binding energy used for molecular dynamic simulation. Immuno-informatics analysis, Molecular Docking and Molecular simulation indicated that epitope peptide vaccine could work as effective peptides helpful in scheming peptide vaccine against <i>B. abortus</i> infection by developing broad-spectrum peptide vaccine in near future. The use of Omp25 as a vaccine candidate has been supported based on previous experimental studies. Multitope vaccine can be developed which can protect mice against virulent <i>B. abortus</i> challenge.抗布鲁氏菌病的减毒活疫苗组合物对受种动物存在潜在风险。因此，本研究采用计算机模拟（in-silico）方法，设计一款新型多表位疫苗肽段，以诱导针对流产布鲁氏菌（Brucella abortus）感染的理想免疫应答。本研究基于流产布鲁氏菌的外膜蛋白（outer membrane protein, OMP）设计肽类疫苗，所选OMP序列的抗原性评分达0.7575。研究团队预测了不同长度的T细胞表位，对180条表位肽开展聚类分析，共得到19个聚类簇，其中14个为共识聚类簇，5个为单例聚类簇。筛选出排名前三的聚类簇，其包含24条具备抗原特性的肽段。将筛选得到的24条抗原肽与主要组织相容性复合体（Major Histocompatibility Complex, MHC）I类和II类分子进行分子对接，并基于结合能选取排名前八的肽段用于后续分子动力学模拟。免疫信息学分析、分子对接与分子动力学模拟结果显示，该表位肽疫苗具备良好应用潜力，可为未来开发针对流产布鲁氏菌感染的广谱肽类疫苗提供指导。既往实验研究已证实，Omp25可作为候选疫苗靶点。后续可开发多表位疫苗，以保护小鼠免受强毒力流产布鲁氏菌的攻击。