Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion.
Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion.
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SARS-CoV-2 BA.2.87.1 和 JN.1 变体在免疫逃避、抗原性和细胞-细胞融合方面的独特模式。
DOI：
10.1101/2024.03.11.583978
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Liu,Shan-
中科院分区：
文献类型：
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作者：
Li,Pei;Liu,Yajie;Faraone,Julia;Hsu,ChengChih;Chamblee,Michelle;Zheng,Yi-Min;Carlin,Claire;Bednash,JosephS;Horowitz,JeffreyC;Mallampalli,RamaK;Saif,LindaJ;Oltz,EugeneM;Jones,Daniel;Li,Jianrong;Gumina,RichardJ;Liu,Shan-
SARS-CoV-2变异株的快速进化对全球疫苗接种工作提出了持续的挑战。在这项研究中，我们对两个新出现的变体BA.2.87.1和JN.1进行了全面的调查，重点是它们的中和抗性，感染性，抗原性，细胞-细胞融合和刺突加工。在不同队列中评估中和抗体（nAb）滴度，包括接受二价mRNA疫苗加强剂的个体、在BA.2.86/JN.1波期间感染的患者和接种XBB.1.5单价疫苗的仓鼠。我们发现，与JN.1和XBB.1.5相比，BA.2.87.1显示出从WT-BA.4/5二价mRNA疫苗接种和JN.1波突破感染血清中少得多的nAb逃逸。有趣的是，与BA.2.86/JN.1和XBB.1.5相比，BA.2.87.1对XBB.1.5单价接种仓鼠血清的中和更具抗性，但可被III类单克隆抗体S309有效中和，而后者在很大程度上无法中和BA.2.86/JN.1。重要的是，BA.2.87.1表现出比BA.2.86/JN.1更高水平的感染性、细胞-细胞融合活性和弗林蛋白酶切割效率。在抗原性上，我们发现BA.2.87.1与最近出现的其他Omicron亚变体（包括BA.2.86/JN.1和XBB.1.5）相比更接近祖先BA.2。总之，这些结果突出了免疫逃逸特性以及生物学的新变种，并强调了持续监测和知情决策的重要性，在发展有效的vaccine.IMPORTANCEThis研究调查最近出现的SARS-CoV-2变种，BA.2.87.1和JN.1，在早期的变种和亲本D 614 G相比。这些变体之间不同的感染性和细胞-细胞融合活性表明它们感染靶细胞的能力以及可能的发病机制存在潜在差异。与JN.1相比，BA.2.87.1从二价mRNA疫苗接种者和BA.2.86/JN.1感染的血清中表现出较低的nAb逃逸，但对XBB.1.5接种的仓鼠血清具有相对抗性，这揭示了免疫原因的独特性质，并强调了继续监测变体和重新配制疫苗的重要性。BA.2.87.1和其他早期变体之间的抗原差异不仅为抗体逃避，而且为病毒进化提供了关键信息。总之，这项研究及时揭示了新出现的变异体BA.2.87.1和JN.1的刺突生物学和免疫逃逸，从而指导有效的疫苗开发并为公共卫生干预提供信息。
The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly, BA.2.87.1 is more resistant to neutralization by XBB.1.5-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines.IMPORTANCEThis study investigates the recently emerged SARS-CoV-2 variants, BA.2.87.1 and JN.1, in comparison to earlier variants and the parental D614G. Varied infectivity and cell-cell fusion activity among these variants suggest potential disparities in their ability to infect target cells and possibly pathogenesis. BA.2.87.1 exhibits lower nAb escape from bivalent mRNA vaccinee and BA.2.86/JN.1-infected sera than JN.1 but is relatively resistance to XBB.1.5-vaccinated hamster sera, revealing distinct properties in immune reason and underscoring the significance of continuing surveillance of variants and reformulation of vaccines. Antigenic differences between BA.2.87.1 and other earlier variants yield critical information not only for antibody evasion but also for viral evolution. In conclusion, this study furnishes timely insights into the spike biology and immune escape of the emerging variants BA.2.87.1 and JN.1, thus guiding effective vaccine development and informing public health interventions.