影响近期KP.3.1.1类SARS-CoV-2变异的功能和抗原性的突变
Bernadeta Dadonaite1, Sheri Harari1, Brendan B Larsen1
1Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, Washington, 98109, USA.
bioRxiv : the preprint server for biology
|September 2, 2025
概括
SARS-CoV-2 的突变突变正在进化以逃避抗体,影响疫苗和治疗的有效性. 了解这些变化有助于预测未来的病毒演变,并告知抗体反应.
科学领域:
- 病毒学和免疫学
- 分子生物学
- 进化生物学
背景情况:
- 严重急性呼吸系统综合征-冠状病毒-2 (SARS-CoV-2) 呈现出快速演变,特别是在其尖端蛋白中.
- 尖端蛋白的突变可以改变它与人类ACE2受体的相互作用,并逃避中和抗体.
- 了解这些进化压力对于开发有效的疫苗和治疗方法至关重要.
研究的目的:
- 调查KP.3.1.1株的SARS-CoV-2突变对病毒性质的影响.
- 评估这些突变如何影响人体血清和临床相关抗体的中和.
- 阐明SARS-CoV-2的进化轨迹及其对公共健康的影响.
主要方法:
- 基于伪病毒的深度突变扫描用于分析尖端蛋白突变.
- 测试测量了细胞进入,ACE2受体结合和受体结合域 (RBD) 构造变化的影响.
- 评估了人类血清和针对突变尖端蛋白的特定单克隆抗体的中和能力.
主要成果:
- 尖端突变对人类血清的中和有显著影响,其影响因先前的疫苗接种或感染史而有所不同.
- 在RBD (例如,在位点475,478,487) 和RBD之外的关键突变 (影响RBD运动) 大大降低了抗体中和.
- 量化了突变对特定抗体 (VYD222,BD55-1205,SA55) 的中和的影响.
结论:
- SARS-CoV-2 尖端蛋白的进化是由选择压力驱动的,以逃避多克隆抗体中和.
- 疫苗接种和感染史改变了抗体反应的等级,影响了哪些突变最具影响力.
- 这些发现提供了SARS-CoV-2演变的见解,并可以帮助预测疫苗和抗体有效性的抗原漂移.
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