一种SARS-CoV-2变种诱导的NTD向抗体通过独特的结合方式增强病毒感染
Wenting Li1, Congcong Liu1, Yaning Li2,3
1Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province, China.
PLoS pathogens
|February 10, 2026
概括
德尔塔变种的SARS-CoV-2仍然可以诱导增强感染的抗体 (NIEAs),这些抗体针对与早期菌株相似的部位. 然而,这些抗体对较新的Omicron变体的活性降低,突出显示病毒进化.
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:
- 感染SARS-CoV-2会产生针对像NTD这样的尖端蛋白域的抗体.
- 一些针对N端域 (NTD) 的抗体可以独立于它们的Fc区域来增强病毒感染.
- 带有NTD突变的SARS-CoV-2变种导致免疫逃避,这引发了关于NIEA诱导的问题.
研究的目的:
- 调查SARS-CoV-2变种,特别是三角洲变种,是否仍然可以诱导针对NTD的增强感染抗体 (NIEAs).
- 来自感染Delta变异的供体的新发现NIEA的结合性和功能性质的特征.
- 了解NIEA认可的结构基础及其对病毒进化和疫苗设计的影响.
主要方法:
- 单克隆抗体 (mAbs) 的分离和表征来自感染Delta变异的供体.
- 在体外评估病毒感染增强的鉴定NIEAs对各种SARS-CoV-2变体.
- 结构分析 (例如,冷-EM) 来确定NIEA的绑定机制和表位识别.
- 对NIEA结构和表位的比较分析与原型菌株诱导NIEAs的比较分析.
主要成果:
- 一个新的NIEA,Cond-854,从一个感染Delta变异的供体中鉴定出来,具有广泛的感染增强活性,可以对抗Omicron前变异,但不能对抗Omicron后变异.
- 与原型NIEAs相比,Cond-854使用Fc独立的双价结合机制,针对一个保存的表位,在重光链方向上与原型NIEAs不同.
- 德尔塔变异NTD突变超出了保存的增强感染的表位,解释了NIEAs的持续诱导.
结论:
- 感染Delta变种的初级感染仍然可以诱导NIEAs向类似于原型菌株诱导的表位.
- 德尔塔NTD内的突变不会显著影响NIEA诱导,因为它们位于临界表位外.
- 为NIEA-病毒表位识别定义了一个独特的结构范式,有助于理解抗病毒抗体反应,并为未来的疫苗策略提供信息.
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