高度保护性精确疫苗针对支原体肺的集成结构蛋白质组学和机器学习引导的映射

支原体肺（M.肺）是一种通常与前列腺癌有关的新兴呼吸道感染，并且在支原体下被分类。由于当前的抗生素处理频繁地完全消除了从宿主中消除这些病原体的频繁无效性，因此对支原体感染的治疗改善至关重要。这项研究的目的是设计和构建由结构蛋白质组学和机器学习算法引导的有效和保护性疫苗，以提供针对肺部感染的保护。通过彻底检查肺杆菌的整个蛋白质组，已经鉴定出四个特定靶标膜蛋白p80，脂蛋白，未表征的蛋白质和含GGDEF结构域的蛋白质，以设计疫苗。使用人工和经常性的神经网络，蛋白质经过了细胞毒性T淋巴细胞（CTL），辅助T淋巴细胞（HTL）-γ±和B-Cell表位的作图。该设计涉及创建mRNA和基于肽的疫苗，该疫苗由GGS连接器，7 HTL（IFN阳性）表位和8个由GPGPG接头加入的8个CTL表位组成。该疫苗设计的表现出抗原行为，非过敏性品质和特殊的物理化学属性。结构建模表明，正确的折叠对于最佳功能至关重要。通过分子对接实验检查了MEVC和Toll样受体（TLR）1，TLR2和TLR6的耦合。随后进行了分子模拟研究，其中包括结合自由能估计。结果表明，相互作用的动力学是稳定的，结合很强。在计算机克隆和优化分析中，GC含量为49.776％，CAI为0.982的优化序列。免疫模拟结果显示出强烈的免疫反应，在IgM+IgG和二次免疫反应中，活性和血浆B细胞水平升高，调节T细胞，HTL和CTL。到第50天，抗原已完全清除。这项研究奠定了基础，为创建有效且安全的疫苗候选者与新近确定的肺肺部感染作斗争。

Mycoplasma pulmonis (M. pulmonis) is an emerging respiratory infection commonly linked to prostate cancer, and it is classified under the group of mycoplasmas. Improved management of mycoplasma infections is essential due to the frequent ineffectiveness of current antibiotic treatments in completely eliminating these pathogens from the host. The objective of this study is to design and construct effective and protective vaccines guided by structural proteomics and machine learning algorithms to provide protection against the M. pulmonis infection. Through a thorough examination of the entire proteome of M. pulmonis, four specific targets Membrane protein P80, Lipoprotein, Uncharacterized protein and GGDEF domain-containing protein have been identified as appropriate for designing a vaccine. The proteins underwent mapping of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) (IFN)-γ ±, and B-cell epitopes using artificial and recurrent neural networks. The design involved the creation of mRNA and peptide-based vaccine, which consisted of 8 CTL epitopes associated by GGS linkers, 7 HTL (IFN-positive) epitopes, and 8 B-cell epitopes joined by GPGPG linkers. The vaccine designed exhibit antigenic behavior, non-allergenic qualities, and exceptional physicochemical attributes. Structural modeling revealed that correct folding is crucial for optimal functioning. The coupling of the MEVC and Toll-like Receptors (TLR)1, TLR2, and TLR6 was examined through molecular docking experiments. This was followed by molecular simulation investigations, which included binding free energy estimations. The results indicated that the dynamics of the interaction were stable, and the binding was strong. In silico cloning and optimization analysis revealed an optimized sequence with a GC content of 49.776 % and a CAI of 0.982. The immunological simulation results showed strong immune responses, with elevated levels of active and plasma B-cells, regulatory T-cells, HTL, and CTL in both IgM+IgG and secondary immune responses. The antigen was completely cleared by the 50th day. This study lays the foundation for creating a potent and secure vaccine candidate to combat the newly identified M. pulmonis infection in people.