通过使用冷-EM直接从免疫血清中发现功能性和表位特异性单克隆抗体
James A Ferguson1, Sai Sundar Rajan Raghavan1, Garazi Peña Alzua2,3
1Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Science advances
|August 15, 2025
概括
这项研究提出了一种更快,更精确的方法,通过分析冷电子显微镜 (cryo-EM) 数据来发现治疗抗体. 改进的工作流加速了抗体序列的确定,有助于疫苗开发和药物发现.
科学领域:
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
- 生物信息学是一种生物信息学.
背景情况:
- 抗体是重要的治疗方法,但传统的发现方法缓慢且难以扩展.
- 目前的方法限制了抗体序列的高通量分析.
研究的目的:
- 通过从冷电子显微镜 (cryo-EM) 数据推断抗体序列来简化抗体发现.
- 为了加快保护性抗体的鉴定,用于治疗的开发.
主要方法:
- 结合结构分析和生物信息学,从血清衍生多克隆抗体 (pAbs) 的冷-EM地图中确定抗体重链和轻链序列.
- 使用ModelAngelo,一种自动化结构构建工具,用于加速序列确定和识别B细胞目录中的序列匹配,使用隐藏的马尔科夫模型 (HMM).
主要成果:
- 与传统方法相比,减少了抗体序列分析时间,从几周减少到不到一天,精度更高.
- 在接种流感疫苗后,成功鉴定了来自小鼠免疫血清的保护性抗体.
- 使用非人类灵长类动物HIV疫苗试验数据验证了管道.
结论:
- 增强的工作流显著提高了绘制多克隆抗体反应的速度和准确性.
- 这种方法在加速疫苗开发和发现新型治疗抗体方面具有广泛的应用.
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