Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1^A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.

对冠状病毒的中和抗体反应主要针对三聚体刺突的受体结合域 （RBD）。在这里，我们表征了 COVID-19 恢复个体的多克隆免疫球蛋白 G （IgG） 和 Fabs，以识别冠状病毒的峰值。血浆 IgG 在关注 RBD 表位、识别 α 和 β 冠状病毒以及亲和力对增加 IgG 结合/中和作用的贡献方面有所不同。使用电子显微镜，我们检查了多克隆血浆 Fab 的特异性，揭示了 SARS-CoV-2 刺突上 S1^A 和 RBD 表位的识别。此外，中和单克隆 Fab-spike 复合物的 3.4 Å 冷冻电子显微镜 （cryo-EM） 结构揭示了阻断 ACE2 受体结合的表位。基于这些结构的建模表明 IgG 在病毒上发生刺突交联的可能性不同，并且表征的 IgG 不会受到已鉴定的 SARS-CoV-2 刺突突变的影响。总体而言，我们的研究在结构上定义了源自 VH3/VH3-66 的复发性抗 SARS-CoV-2 抗体类别以及与 SARS-CoV VH3-30 抗体的相似性，为评估疫苗引发的抗体提供了标准。