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尖端的S2子单元编码了针对SARS-CoV-2的功能性抗体反应的多种标

Jamie Guenthoer¹, Meghan E Garrett¹, Michelle Lilly¹

¹Human Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America.

|August 2, 2024

概括

针对SARS-CoV-2的S2区域的新抗体提供了对变种和其他冠状病毒的广泛中和. 这些S2抗体显示出未来的流行病准备和更广泛的人类冠状病毒反应的潜力.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
结构生物学结构生物学

背景情况:

SARS-CoV-2 进化驱动免疫逃避,降低疫苗和治疗疗效.
在S1亚单元的受体结合域中的突变允许病毒从抗体中逃脱.
专注于像S2子域这样的保护区域对于广泛的抗病毒策略至关重要.

研究的目的:

识别和描述针对SARS-CoV-2尖端蛋白的S2亚域的抗体.
评估S2特异单克隆抗体 (mAbs) 的中和能力和范围.
研究S2 mAbs与其他冠状病毒的交叉活性以及调解抗体依赖细胞毒性 (ADCC) 的潜力.

主要方法:

从康复个体中分离和鉴定S2特异性单克隆抗体 (mAbs).
具有约束力的测试以确定S2子域内的表位标.
对SARS-CoV-2变种,SARS-CoV-1和动物性沙贝科病毒的病毒中和测试.
对抗体依赖细胞细胞毒性 (ADCC) 活动的评估.
与其他人类冠状病毒 (HCoV) 的尖端蛋白进行交叉反应性分析.

主要成果:

确定了针对S2子域内的不同区域的S2 mAbs,包括保存的表位.
一个S2 mAb,C20.119,在SARS-CoV-2变种,SARS-CoV-1和相关的萨尔贝科病毒中表现出广泛的中和.
许多非中和的S2 mAbs表现出显著的抗体依赖细胞细胞毒性 (ADCC).
一些具有ADCC功能的S2 mAbs与MERS-CoV和HCoV-HKU1.1的尖端蛋白具有交叉反应性.

结论:

S2 mAbs可以准尖端蛋白的保存和功能重要区域.
S2 mAbs具有广泛的中和和ADCC能力,具有针对不同类型的萨尔贝科病毒和HCoVs的潜力.
这些发现凸显了S2表位作为开发广泛的冠状病毒治疗方法和疫苗的有希望的目标,用于未来的流行病.

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