The Omicron variant of SARS-CoV-2 evades antibody-mediated neutralization with unprecedented efficiency. At least three Omicron sublineages have been identified—BA.1, BA.2, and BA.3—and BA.2 exhibits increased transmissibility. However, it is currently unknown whether BA.2 differs from the other sublineages regarding cell entry and antibody-mediated inhibition. Here, we show that BA.1, BA.2, and BA.3 enter and fuse target cells with similar efficiency and in an ACE2-dependent manner. However, BA.2 was not efficiently neutralized by seven of eight antibodies used for COVID-19 therapy, including Sotrovimab, which robustly neutralized BA.1. In contrast, BA.2 and BA.3 (but not BA.1) were appreciably neutralized by Cilgavimab, which could constitute a treatment option. Finally, all sublineages were comparably and efficiently neutralized by antibodies induced by BNT162b2 booster vaccination after previous two-dose homologous or heterologous vaccination. Collectively, the Omicron sublineages show comparable cell entry and neutralization by vaccine-induced antibodies but differ in susceptibility to therapeutic antibodies.

SARS-CoV-2 的 Omicron 变体以前所未有的效率逃避了抗体介导的中和作用。至少已经确定了三个 Omicron 亚系——BA.1、BA.2 和 BA.3——并且 BA.2 表现出更高的传播能力。然而，目前尚不清楚 BA.2 在细胞进入和抗体介导的抑制方面是否与其他亚系不同。在这里，我们显示 BA.1、BA.2 和 BA.3 以类似的效率和 ACE2 依赖性方式进入和融合靶细胞。然而，BA.2 没有被用于 COVID-19 治疗的八种抗体中的七种有效中和，包括 Sotrovimab，它可以强力中和 BA.1。相反，BA.2 和 BA.3（但不是 BA.1）被 Cilgavimab 明显中和，这可能构成一种治疗选择。最后，在先前的两剂同源或异源疫苗接种后，所有亚系都被 BNT162b2 加强疫苗接种诱导的抗体同等有效地中和。总的来说，Omicron 亚系显示出相当的细胞进入和疫苗诱导抗体的中和作用，但对治疗性抗体的易感性不同。