身体突变引入了旁观者突变,为新出现的变种准备SARS-CoV-2抗体
Michael Korenkov1, Matthias Zehner1, Hadas Cohen-Dvashi2
1Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Immunity
|November 30, 2023
概括
身体突变 (SHM) 增强了SARS-CoV-2变种的抗体中和. 虽然突变可以降低功能,但它们对于中和Omicron变种至关重要,从而使新的抗体疗法的开发成为可能.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 身体突变 (SHM) 对于抗体亲和力成熟至关重要.
- 目前正在进行的SHM在SARS-CoV-2中和抗体 (nAb) 对进化的变体有效性的作用仍然不完全理解.
- 一些强大的nAbs表现出最小的或没有突变,质疑SHM对中和的必要性.
研究的目的:
- 研究可变区域突变对SARS-CoV-2 nAbs. 的结合和中和能力的影响.
- 确定SHM如何对抗不同SARS-CoV-2变体的抗体反应作出贡献,包括Omicron.
- 通过了解SHM的作用来设计增强的nAbs.
主要方法:
- 在92个SARS-CoV-2 nAbs. 中可变区域突变的逆转.
- 对抗体结合亲和力和中和力对抗SARS-CoV-2菌株 (Wu01,Alpha,Beta,Delta,Omicron BA.1/BA.2) 的评估.
- 突变抗体与逆转抗体的功能特征.
主要成果:
- 逆转突变通常与抗体功能下降相关.
- 某些抗体,如VH1-58克隆型的抗体,在突变逆转后保持了Wu01的中和.
- 突变对于中和早期变异是不可或缺的,但对于VH1-58抗体对Omicron BA.1/BA.2中和至关重要.
- 临床抗体tixagevimab成功地被设计为奥米克朗BA.1/BA.2中和.
结论:
- SHM具有双重作用:增强亲和力成熟和多样化抗体反应,以对抗病毒逃生变体.
- 抗体突变,虽然有时是有害的,但对于中和较新的SARS-CoV-2变种 (如Omicron) 是必不可少的.
- 了解SHM机制可以合理设计广泛中和抗体来对抗不断演变的病毒.
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