在体内抗体多样化,准保存的冠状病毒表位
Usha Nair1, Ziqi Feng2, Madhav Akauliya1
1The Ragon Institute of Mass General, MIT, and Harvard , Cambridge, MA, USA.
The Journal of experimental medicine
|July 17, 2025
概括
表达B细胞受体 (BCR) 的人性化小鼠模型产生了针对SARS-CoV-2变种和相关冠状病毒的广泛中和抗体. 这种方法使抗体反应多样化,以改善病毒表位素向.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- CR3022单克隆抗体 (mAb) 针对SARS-CoV.的受体结合域 (RBD) 上的一种保存表位.
- 对抗体反应的多样化对于对抗如SARS-CoV-2等不断变化的病毒威胁至关重要.
研究的目的:
- 为了研究人类B细胞受体 (BCR) 敲入小鼠扩大抗体反应的实用性.
- 使用BCR敲进小鼠,对SARS-CoV-2和相关的冠状病毒进行增强抗体的工程.
主要方法:
- 用SARS-CoV-2武汉RBDtrimers对高和低亲和CR3022BCR敲进小鼠进行免疫接种.
- 对抗体亲和力的表征,中和幅度,以及关键突变的结构分析.
主要成果:
- 生成的抗体保留了SARS-CoV中和,并显示了对SARS-CoV-2菌株和变种 (三角形,Omicron KP.3) 的增强亲和力和中和.
- 观察到对蝙蝠冠状病毒WIV1和BtKY72.2的扩大反应性.
- 结构分析发现了对增强结合和中和至关重要的突变.
结论:
- 人类BCR表达的小鼠模型有效产生具有广泛中和活性的抗体来对抗病毒表位.
- 这一战略有望开发下一代抗体治疗药物来对抗各种冠状病毒.
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