人类抗体针对冠状病毒尖峰S2亚单元的向与Fc效应器功能介导的保护有关
Krithika Muthuraman1,2, Matthew Jackman1, Yu Liang3
1Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Journal of virology
|November 12, 2025
概括
一种新的人类抗体 (mAb 1871) 针对β冠状病毒 (β-CoVs) 的保存的S2子单元,提供广泛的结合和中和. 这种抗体在体内提供保护,突出显示S2亚单元是未来大流行对策的目标.
科学领域:
- 病毒学和免疫学 病毒学和免疫学
- 传染性疾病 传染性疾病
- 生物医学对策 生物医学对策
背景情况:
- 由于经常发生的流行病和大流行病,β-CoVs构成了重大威胁,需要广泛的抗病毒策略.
- 现有的针对SARS-CoV-2的受体结合域 (RBD) 向抗体由于病毒进化而表现出局限性.
- 冠状病毒尖端蛋白的S2亚单元在β-CoV中比S1亚单元更保守,为更广泛的治疗开发提供了潜在的目标.
研究的目的:
- 描述一种新型的人类单克隆抗体 (mAb 1871),针对β-CoVs的S2亚单元.
- 研究mAb 1871对β-CoVs的结合,中和能力和作用机制.
- 评估mAb 1871的治疗潜力,包括其 in vivo 的疗效和 Fc 依赖功能.
主要方法:
- 使用冷电子显微镜测定了mAb 1871与S2亚单元的结合部位和分子相互作用.
- 在体外测试中评估了抗体在各种β-CoV的结合宽度及其对SARS-CoV-2的中和作用.
- 在小鼠模型中的体内研究评估了mAb 1871的保护功效,重点关注Fc效应器功能的作用.
主要成果:
- mAb 1871与S2子单元上游螺旋上的保存表位结合,解释了其交叉反应性.
- 该抗体表现出广泛的β-CoV结合和中和sarbecoviruses,尽管其强度低于一些RBD特异性抗体.
- mAb 1871在小鼠模型中给予了显著的保护,在体内有效性方面严重依赖Fc效应器功能.
结论:
- 由mAb 1871准的S2亚单元中的一个保存的表位体代表了开发广谱β-CoV对策的有希望的目标.
- 对于S2-定向抗体的体内保护活性,Fc效应器功能至关重要.
- 这些发现支持开发泛β-CoV疗法和针对尖蛋白保护区域的疫苗.
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