Shahraki Parisa Kh, Kiani Razie, Siavash Mansour, Bemani Peyman
Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Sci Rep. 2025 Apr 25;15(1):14517. doi: 10.1038/s41598-025-85147-3.
Development of a strategy to combat Staphylococcus aureus is a high priority for the World Health Organization. B cell and helper T lymphocyte (HTL) epitopes of leukotoxin ED (LukED) were predicted using computational tools. The predicted epitopes were screened for conservancy, allergenicity, toxicity, autoreactivity, and population coverage. The immunogenic regions of LukED were linked together and to Human β-defensin 3 (hBD3) as adjuvant with appropriate linkers. The predicted 3D structure of the vaccine validated by molecular dynamics (MD) simulations. Subsequently, the 3D structure was docked with the Toll-like receptor (TLR)1/2 to evaluate the binding capacity of the adjuvant. Finally, MD simulation was employed to characterizing the conformational dynamics and stability of this interaction. The predicted epitopes were found to be non-toxic and non-allergenic, with no homology to the human proteome. The vaccine demonstrated a population coverage of 65.15% globally. It was composed of the immunogenic regions of LukED. Molecular docking and MD simulation indicated a stable interaction between hBD3 in the vaccine and TLR1/2 during the simulation period. We have designed vaccine against S. aureus LukED that targets epitope-rich regions, which helps maintain a native-like conformation. This work lays the groundwork for further experimental studies to evaluate the vaccine's neutralizing effects.
制定对抗金黄色葡萄球菌的策略是世界卫生组织的一项高度优先事项。使用计算工具预测白细胞毒素ED（LukED）的B细胞和辅助性T淋巴细胞（HTL）表位。对预测的表位进行保守性、致敏性、毒性、自身反应性和人群覆盖率筛选。LukED的免疫原性区域通过适当的接头连接在一起，并与作为佐剂的人β-防御素3（hBD3）相连。通过分子动力学（MD）模拟验证了疫苗的预测三维结构。随后，将三维结构与Toll样受体（TLR）1/2对接，以评估佐剂的结合能力。最后，采用MD模拟来表征这种相互作用的构象动力学和稳定性。发现预测的表位无毒且无致敏性，与人类蛋白质组无同源性。该疫苗在全球范围内的人群覆盖率为65.15%。它由LukED的免疫原性区域组成。分子对接和MD模拟表明，在模拟期间疫苗中的hBD3与TLR1/2之间存在稳定的相互作用。我们设计了针对金黄色葡萄球菌LukED的疫苗，该疫苗靶向富含表位的区域，有助于维持类似天然的构象。这项工作为进一步评估疫苗中和作用的实验研究奠定了基础。
