SARS-CoV-2尖端变体的中和抗性主要由协同作用的受体结合域替代介导
Long V Pham1,2, Alexander P Underwood1,2, Alekxander Binderup1,2
1Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.
Emerging microbes & infections
|October 11, 2024
概括
新的SARS-CoV-2变种,包括Omicron JN.1衍生物,对中和抗体的抗性增加. 在受体结合域之外的尖端蛋白质变化也会导致抗体逃避和改变ACE2依赖.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 随着SARS-CoV-2的进化,已经产生了许多具有改变尖峰糖蛋白的关注变体 (VOC).
- 奥米克朗亚系对感染或接种疫苗的中和抗体 (nAbs) 具有抗性,特定的尖端蛋白变化不明.
研究的目的:
- 研究在VOC中发现的特定SARS-CoV-2尖端蛋白突变对抗体中和ACE2受体使用的影响.
- 阐明受体结合域 (RBD) 和非RBD尖端突变在病毒免疫逃避中的作用.
主要方法:
- 使用反向遗传学生成具有VOC特异性尖端突变的传染性SARS-CoV-2突变病毒.
- 用康复和接种疫苗的个人血测量病毒对抗体中和的敏感性.
- 通过抗体阻断和siRNA进行病毒进入的ACE2使用的评估,以及ACE2结合亲缘关系的表面等离子体共振.
主要成果:
- 在RBD中组合的尖端蛋白替代物协同增加了中和抵抗.
- 具有整个VOC尖端蛋白的突变病毒显示出增强的耐药性,表明非RBD变化是显著的.
- 奥米克朗BA.2.86和JN.1突变显示出减少了ACE2对进入的依赖性,但增加了ACE2结合亲和力.
结论:
- 特定的SARS-CoV-2尖端蛋白变化,包括RBD之外的变化,驱动中和抗体逃避.
- 在最近的VOC中,病毒进入机制发生了变化,这对了解SARS-CoV-2进化和免疫逃逸有影响.
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