亲和力成熟赋予了对SARS-CoV-2第6类广泛中和抗体的强有力的活性
Ohan Mazigi1,2, David B Langley1,2, Jake Y Henry1,2
1Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
概括
针对一个神秘的SARS-CoV-2表位体的高亲缘性抗体中和了令人担忧的变体. 皮科莫拉亲和力对于强大的中和和对SARS-CoV-2的长期免疫是至关重要的.
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:
- 新出现的SARS-CoV-2令人担忧的变种 (VOCs) 降低了现有的单克隆抗体 (mAbs) 的疗效.
- 针对神秘受体结合域 (RBD) 表位体的抗体表现出广泛的活性,但中和,阻碍了临床使用.
研究的目的:
- 识别和增强针对SARS-CoV-2尖端蛋白的神秘类6表位的抗体.
- 调查高抗体亲和度在中和SARS-CoV-2VOC和提供保护中的作用.
主要方法:
- 在体外显示技术用于抗体识别和亲和力成熟.
- 抗体-RBD复合物的冷电子显微镜和晶体结构分析.
- 在 hACE2小鼠中进行病毒中和测定和体内保护研究.
主要成果:
- 通过亲和力成熟的抗体实现了皮科莫拉结合亲和力.
- 这些抗体有效地中和了SARS-CoV-2的VOC,并保护小鼠免受感染.
- 结构分析揭示了远离常见VOC突变部位的表位.
结论:
- 非常高的抗体亲和力 (picomolar范围) 对于有效中和SARS-CoV-2变种至关重要.
- 6类表位抗体存在于自然免疫系统中,可以诱导.
- 实现高亲和力对于开发针对SARS-CoV-2的有效疫苗和治疗方法至关重要.
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