IgG3亚类抗体通过高效的双价结合来识别抗原漂移流感病毒和SARS-CoV-2变体
Marcus J Bolton1, Jefferson J S Santos1, Claudia P Arevalo1
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
概括
抗体IgG子类显著影响病毒结合和中和,特别是在流感和SARS-CoV-2等漂移病毒中. 与IgG1.1相比,IgG3对抗原不匹配的标显示出更高的疗效.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 抗体常数域 (Fc区域) 对于效应器功能至关重要.
- 对于IgG子类对抗体结合和中和的影响,特别是对漂移病毒的影响,尚未完全理解.
研究的目的:
- 研究不同的人类IgG子类 (IgG1,IgG2,IgG3) 如何影响单克隆抗体 (mAbs) 的结合和中和能力.
- 为了确定IgG子类的影响是否更明显,由于抗原漂移而减少了抗原亲和力.
主要方法:
- 对人类流感和SARS-CoV-2单克隆抗体的评估小组被设计成IgG1,IgG2和IgG3亚类.
- 评估了对同源和抗原漂移病毒菌株的抗体结合和中和能力.
- 在IgG3与IgG1格式中比较了一种授权的治疗mAb的性能.
主要成果:
- 流感和SARS-CoV-2 mAbs表现出基于其IgG子类的改变结合和中和.
- 当抗原亲和力因抗原不匹配而降低时,子类介导的疗效差异最为显著.
- IgG3抗体对抗原漂移流感病毒和SARS-CoV-2变种的结合和中和有所增强.
- 治疗的mAb保留了针对SARS-CoV-2变种的中和幅度,作为IgG3,但不是IgG1.
结论:
- IgG子类在调节抗体结合和中和方面发挥着至关重要的作用,不仅仅是效应器功能.
- 选择IgG亚类对于开发有效的抗体来对抗流感和SARS-CoV-2等抗原变异病毒很重要.
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