在野生驼中对MERS-CoV进行解码抗体反应
Faten Idoudi1,2,3, Ruoke Wang2, Long Tian4,5,6
1Pasteur Institute of Tunis, Laboratory of Biomolecules, Venoms and Theranostic Applications (LR20IPT01), NanoBioMedika research Team, University Tunis El Manar, Tunis 1002, Tunisia.
概括
野生驼拥有对中东呼吸综合征冠状病毒 (MERS-CoV) 的抗体,新型纳米体显示对MERS-CoV受体结合域突变的强效中和,具有治疗潜力.
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:
- 非洲和阿拉伯半岛的野生驼有针对中东呼吸综合征冠状病毒 (MERS-CoV) 的抗体.
- 这些驼抗体的特征,包括强度和特异性,尚不清楚.
- 了解驼免疫力对于开发MERS-CoV治疗方法至关重要.
研究的目的:
- 描述突尼斯自然感染MERS-CoV的野生驼的抗体反应.
- 识别和结构分析具有对MERS-CoV.有强大的中和活性的新型纳米体 (VHHs).
- 探索这些纳米体对MERS-CoV预防和治疗发展的潜力.
主要方法:
- 来自9只突尼斯驼的血抗体的表征.
- 从驼外周血液单核细胞 (PBMC) 产生和选一个VHH抗体库.
- 亲和结合试验,对MERS-CoV受体结合域 (RBD) 突变物进行中和试验,以及对VHHs的晶体结构分析.
主要成果:
- 驼血抗体显示出可变的,与年龄相关的中和活性,主要是自身的.
- 确定了34个独特的VHH序列,具有新的生殖系起源和长CDR3区域.
- 八个VHHs表现出与MERS-CoV RBD的高亲和力结合和RBD突变的广泛中和 (IC50:1.05-9.55 ng/mL). 结构分析揭示了不同的中和机制,包括阻止DPP4结合和准RBD核心.
结论:
- 野生驼有针对MERS-CoV的抗体反应,其特征是新的纳米体.
- 已识别的纳米体显示出MERS-CoV RBD突变体的广泛和强大的中和.
- 这些发现提供了关于驼免疫力的见解,并突出了MERS-CoV治疗方法的有希望的候选人.
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