在SARS-CoV-2变种和SARS-CoV交叉中和后面的B细胞基因组学
Johannes F Scheid1, Christopher O Barnes2, Basak Eraslan3
1Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Cell
|May 20, 2021
概括
研究人员描述了B细胞对SARS-CoV-2的反应,确定了产生强效中和抗体 (nAbs) 的不同种群. 这些nAbs针对保存的表位,提供对冠状病毒的广泛保护,并为未来的疫苗和治疗设计提供信息.
科学领域:
- 免疫学
- 病毒学
- 结构生物学
背景情况:
- 单克隆抗体 (mAbs) 对于对抗SARS-CoV-2及其变体至关重要.
- 了解B细胞反应是设计有效疫苗和治疗方法的关键.
研究的目的:
- 使用集成的单细胞技术来描述B细胞对SARS-CoV-2的反应.
- 确定有效的中和抗体 (nAbs) 和它们的治疗点.
主要方法:
- 通过单细胞VDJ和RNA测序 (RNA-seq) 进行组合B细胞分类.
- 使用冷电子显微镜确定了nAbs与SARS-CoV-2尖端剪切器复杂的结构.
主要成果:
- 识别了截然不同的B细胞种群,包括产生nAbs的,类似于记忆和激活的B细胞.
- 结构分析显示nAbs针对不同的受体结合域 (RBD) 表位.
- 一个mAb,BG10-19,通过锁定尖端剪切器以封闭的形状来中和SARS-CoV-2,变种 (B.1.1.7,B.1.351).
结论:
- 在SARS-CoV-2特异性B细胞中表现出转录异质性.
- 发现了用于更广泛的冠状病毒保护的交叉中和抗体目标.
- 这些发现将指导下一代免疫原和治疗新冠病毒的设计.
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