来自JN.1的LB.1,KP.2.3,KP.3和KP.3.1.1亚变种的中和和稳定性
Pei Li1,2, Julia N Faraone1,2,3, Cheng Chih Hsu2
1Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA.
bioRxiv : the preprint server for biology
|September 16, 2024
概括
新的SARS-CoV-2变种由于尖端蛋白突变而逃避中和抗体. 这些变种显示感染性降低和稳定性增加,表明需要更新疫苗.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 全球COVID-19在2024年夏季的激增是由SARS-CoV-2变种驱动的,它们是JN.1亚变种的后代.
- 这些变异具有新的突变,特别是在尖端蛋白的N端域 (NTD).
研究的目的:
- 描述新出现的SARS-CoV-2亚型的中和抗体 (nAb) 逃逸,感染性,融合和稳定性 (LB.1,KP.2.3,KP.3,KP.3.1.1).
- 为了研究特定突变的影响,比如在NTD中的位置31 (DelS31) 的血清删除,对病毒性质的影响.
主要方法:
- 对疫苗和先前感染的nAb逃避的评估.
- 在CaLu-3细胞中测试伪病毒感染性.
- 分析尖端蛋白的稳定性,包括S1脱落和耐热性.
- 分子建模以阐明突变的结构影响.
主要成果:
- 所有研究的亚变体都显示出从双价mRNA疫苗,XBB.1.5疫苗和BA.2.86/JN.1感染中显著逃避nAbs.
- 在NTD中的Dels31突变被确定为nAb逃逸和独特的抗原特征的主要驱动因素.
- 德尔S31降低了伪病毒的感染力,并影响了细胞-细胞融合.
- 德尔S31变体的尖端蛋白显示出增强的结构稳定性和减少S1脱落.
- 分子建模表明Dels31稳定了NTD,加强了NTD-RBD相互作用,并有利于RBD下降形态.
- 由Dels31引入的N30的新N结合甘氨酸,可以保护NTD免受抗体识别.
结论:
- NTD突变,特别是Dels31,在SARS-CoV-2 nAb逃避,病毒稳定性和传染性方面发挥着至关重要的作用.
- 这些发现强调需要考虑将含有Dels31的抗原纳入未来的COVID-19疫苗更新,以扩大免疫保护.
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