双特异性抗体通过向ACE2和病毒尖峰来提供新出现的β-冠状病毒的广泛中和
Minghui Li1, Chaoyue Zhao1, Jialu Shi2
1Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People's Republic of China.
Emerging microbes & infections
|September 11, 2024
概括
工程双特异性抗体 (bsAbs) 显示对SARS-CoV-2变种,SARS-CoV和MERS-CoV的广泛中和. IgG-scFv格式表现出卓越的功效,为流行病准备提供了一个有前途的战略.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
背景情况:
- 人类冠状病毒 (SARS-CoV,MERS-CoV,SARS-CoV-2) 是重要的呼吸道病原体.
- 病毒的快速进化,特别是SARS-CoV-2变种,挑战了当前的单克隆抗体疗法.
研究的目的:
- 设计针对病毒尖端蛋白和宿主ACE2受体的新型双特异性抗体 (bsAbs).
- 为了增强对各种β-冠状病毒的中和范围和有效性.
主要方法:
- 使用"Knob-into-Hole"和"IgG-scFv"技术来完成工程学士学位.
- 对伪病毒和真实的SARS-CoV-2变种,SARS-CoV和MERS-CoV.进行了测试的bsAbs.
- 不同的bsAbs格式的中和能力进行比较.
主要成果:
- 设计的bsAbs在测试的冠状病毒和SARS-CoV-2变种中表现出有效的中和.
- 与"Knob-into-Hole"相比",IgG-scFv"的bsAbs格式显示出更好的结合和中和.
- 特定的"IgG-scFv"bsAbs (H11B11_m336) 对24种β冠状病毒伪型 (IC50:0.001-0.183μg/mL) 呈现出高强度.
结论:
- 双特异性抗体代表了对抗现有和新兴的冠状病毒威胁的有效策略.
- 开发的bsAbs增强了中和的广度和效力,改善了流行病的准备.
- "IgG-scFv"格式是开发广泛的冠状病毒疗法的一个有前途的平台.
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