The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 and JN.1 variants, representing >80% of circulating variants in January 2024. The XBB subvariants carry few but recurrent mutations in the spike, whereas BA.2.86.1 and JN.1 harbor >30 additional changes. These variants replicate in IGROV-1 but no longer in Vero E6 and are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals are markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhances NAb responses against both XBB and BA.2.86 variants. JN.1 displays lower affinity to ACE2 and higher immune evasion properties compared to BA.2.86.1. Thus, while distinct, the evolutionary trajectory of these variants combines increased fitness and antibody evasion.

SARS-CoV-2的不断传播导致新型病毒亚系的不断出现。在这里，我们分离并表征了 XBB.1、XBB.1.5、XBB.1.9.1、XBB.1.16.1、EG.5.1.1、EG.5.1.3、XBF、BA.2.86.1 和 JN.1 变体，代表 2024 年 1 月超过 80% 的流通变体。XBB 亚变体在刺突中携带少量但反复出现的突变，而 BA.2.86.1 和 JN.1 则包含超过 30 个额外变化。这些变体在 IGROV-1 中复制，但不再在 Vero E6 中复制，并且不具有明显的融合性。它们能有效感染鼻上皮细胞，其中 EG.5.1.3 表现出最高的适应性。抗病毒药物仍然有效。与 BA.1 相比，疫苗接种者和 BA.1/BA.2 感染个体的中和抗体 (NAb) 反应明显较低，但变体之间没有重大差异。 XBB 突破性感染可增强针对 XBB 和 BA.2.86 变体的 NAB 反应。与 BA.2.86.1 相比，JN.1 对 ACE2 的亲和力较低，免疫逃避特性较高。因此，虽然不同，但这些变体的进化轨迹结合了适应性的增强和抗体逃避。