病毒进化预测识别了对现有和潜在的SARS-CoV-2变体的广泛中和抗体
Fanchong Jian1,2,3, Anna Z Wec4, Leilei Feng5,6
1Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, China.
Nature microbiology
|June 10, 2025
概括
科学家们开发了一种使用深度突变扫描的方法来预测病毒演变,并识别针对SARS-CoV-2变种的广泛中和抗体 (bnAbs). 这种方法显著增加了为未来的流行病准备找到有效bnAbs的机会.
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:
- 针对SARS-CoV-2的治疗单克隆抗体 (mAbs) 受到病毒进化和快速逃逸的限制.
- 开发对未来的SARS-CoV-2变体有效的广泛中和抗体 (bnAbs) 对于持续控制COVID-19至关重要.
研究的目的:
- 预测SARS-CoV-2受体结合域的演变,并选择具有针对当前和未来变异的广泛中和活性的mAbs.
- 评估一种深度突变扫描方法,用于识别广泛中和抗体 (bnAbs).
主要方法:
- 深度突变扫描被用来预测病毒的进化和选择广泛中和抗体.
- 对1103个野生类型引起的mAbs进行了回顾性分析.
- 低温电子显微镜被用于对选定的bnAb.Ab的结构分析.
- 使用mRNA-脂质纳米粒子输送来测试选定的bnAb在小鼠中的疗效.
主要成果:
- 深度突变扫描方法将针对XBB.1.5菌株的有效bnAbs识别概率从1%提高到40%.
- 鉴定到的bnAb,BD55-1205,对所有测试的SARS-CoV-2变种表现出强烈的活性.
- 结构分析揭示了BD55-1205的受体模拟机制,解释了其广泛的反应性.
- 在小鼠中,BD55-1205-IgG的mRNA输送实现了针对多种变异的高中和抗体标位 (XBB.1.5,HK.3.1,JN.1).
结论:
- 将病毒进化预测与深度突变扫描相结合是识别广泛中和抗体的有效策略.
- 鉴定到的bnAb BD55-1205显示为对抗SARS-CoV-2变体的广谱疗法具有前途.
- 这种综合方法与mRNA传递技术相结合,可以加速为SARS-CoV-2和其他潜在的流行病原体开发下一代基于抗体的对策.
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