Department of Reproductive Assistance, Center for Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
PLoS One. 2024 Oct 28;19(10):e0309560. doi: 10.1371/journal.pone.0309560. eCollection 2024.
Brucellosis and Tuberculosis, both of which are contagious diseases, have presented significant challenges to global public health security in recent years. Delayed treatment can exacerbate the conditions, jeopardizing patient lives. Currently, no vaccine has been approved to prevent these two diseases simultaneously. In contrast to traditional vaccines, mRNA vaccines offer advantages such as high efficacy, rapid development, and low cost, and their applications are gradually expanding. This study aims to develop multi-epitope mRNA vaccines argeting Brucella melitensis and Mycobacterium tuberculosis H37Rv (L4 strain) utilizing immunoinformatics approaches. The proteins Omp25, Omp31, MPT70, and MPT83 from the specified bacteria were selected to identify the predominant T- and B-cell epitopes for immunological analysis. Following a comprehensive evaluation, a vaccine was developed using helper T lymphocyte epitopes, cytotoxic T lymphocyte epitopes, linear B-cell epitopes, and conformational B-cell epitopes. It has been demonstrated that multi-epitope mRNA vaccines exhibit increased antigenicity, non-allergenicity, solubility, and high stability. The findings from molecular docking and molecular dynamics simulation revealed a robust and enduring binding affinity between multi-epitope peptides mRNA vaccines and TLR4. Ultimately, Subsequently, following the optimization of the nucleotide sequence, the codon adaptation index was calculated to be 1.0, along with an average GC content of 54.01%. This indicates that the multi-epitope mRNA vaccines exhibit potential for efficient expression within the Escherichia coli(E. coli) host. Analysis through immune modeling indicates that following administration of the vaccine, there may be variation in immunecell populations associated with both innate and adaptive immune reactions. These types encompass helper T lymphocytes (HTL), cytotoxic T lymphocytes (CTL), regulatory T lymphocytes, natural killer cells, dendritic cells and various immune cell subsets. In summary, the results suggest that the newly created multi-epitope mRNA vaccine exhibits favorable attributes, offering novel insights and a conceptual foundation for potential progress in vaccine development.
布鲁氏菌病和结核病都是传染性疾病，近年来对全球公共卫生安全构成了重大挑战。如果治疗不及时，病情可能会恶化，危及患者生命。目前，尚无预防这两种疾病的联合疫苗。与传统疫苗相比，mRNA 疫苗具有高效、快速开发和低成本等优势，其应用正在逐步扩大。本研究旨在利用免疫信息学方法，针对布鲁氏菌 melitensis 和结核分枝杆菌 H37Rv（L4 株）开发多表位 mRNA 疫苗。选择指定细菌中的 Omp25、Omp31、MPT70 和 MPT83 蛋白，以鉴定用于免疫分析的主要 T 细胞和 B 细胞表位。经过全面评估，使用辅助性 T 淋巴细胞表位、细胞毒性 T 淋巴细胞表位、线性 B 细胞表位和构象 B 细胞表位，研制出疫苗。研究表明，多表位 mRNA 疫苗具有增强的抗原性、非变应原性、可溶性和高稳定性。分子对接和分子动力学模拟的研究结果表明，多表位肽 mRNA 疫苗与 TLR4 之间具有强大且持久的结合亲和力。随后，对核苷酸序列进行优化，计算出密码子适应指数为 1.0，平均 GC 含量为 54.01%。这表明多表位 mRNA 疫苗在大肠杆菌（E.coli）宿主中有高效表达的潜力。免疫建模分析表明，疫苗接种后，与固有和适应性免疫反应相关的免疫细胞群体可能会发生变化。这些类型包括辅助性 T 淋巴细胞（HTL）、细胞毒性 T 淋巴细胞（CTL）、调节性 T 淋巴细胞、自然杀伤细胞、树突状细胞和各种免疫细胞亚群。总之，研究结果表明，新构建的多表位 mRNA 疫苗具有良好的特性，为疫苗开发的潜在进展提供了新的见解和概念基础。
