SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor-binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for antibodies. Here, we use NTD-specific probes to capture anti-NTD memory B cells in a longitudinal cohort of infected individuals, some of whom were vaccinated. We found 6 complementation groups of neutralizing antibodies. 58% targeted epitopes outside the NTD supersite, 58% neutralized either Gamma or Omicron, and 14% were broad neutralizers that also neutralized Omicron. Structural characterization revealed that broadly active antibodies targeted three epitopes outside the NTD supersite including a class that recognized both the NTD and SD2 domain. Rapid recruitment of memory B cells producing these antibodies into the plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants, including Omicron.

SARS-CoV-2 感染或疫苗接种会产生中和抗体反应，有助于更好的临床结果。刺突三聚体 (S) 的受体结合结构域 (RBD) 和 N 末端结构域 (NTD) 构成抗体的两个主要中和靶点。在这里，我们使用 NTD 特异性探针来捕获感染个体的纵向队列中的抗 NTD 记忆 B 细胞，其中一些人接种了疫苗。我们发现了 6 个中和抗体的互补组。 58% 的目标表位位于 NTD 超级位点之外，58% 中和 Gamma 或 Omicron，14% 是也中和 Omicron 的广泛中和剂。结构表征表明，广泛活性的抗体靶向 NTD 超级位点之外的三个表位，其中包括同时识别 NTD 和 SD2 结构域的一类表位。再次感染时，产生这些抗体的记忆 B 细胞快速募集到浆细胞区室中，可能有助于随后感染 SARS-CoV-2 变体（包括 Omicron）时相对良性的过程。