Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded antibodies from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found seven major antibody competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of antibody-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. Although emerging SARS-CoV-2 variants of concern escaped binding by many members of the groups associated with the most potent neutralizing activity, some antibodies in each of those groups retained affinity—suggesting that otherwise redundant components of a primary immune response are important for durable protection from evolving pathogens. Our results furnish a global atlas of S-specific memory B cell repertoires and illustrate properties driving viral escape and conferring robustness against emerging variants.

记忆 B 细胞储备可以产生针对重复 SARS-CoV-2 感染的保护性抗体，但从原始感染到抗原漂移变异的范围未知。我们绘制了来自 19 名 COVID-19 恢复期受试者的针对 SARS-CoV-2 刺突 (S) 的记忆 B 细胞受体编码抗体的图表，并发现针对个体中反复靶向的表位的七个主要抗体竞争组。包含已发表的和新确定的抗体-S复合物的结构，确定了相应的表位区域。分组分配与交叉冠状病毒反应广度、中和效力和收敛抗体特征相关。尽管新出现的 SARS-CoV-2 变异体逃脱了与最有效的中和活性相关的组的许多成员的结合，但每个组中的一些抗体保留了亲和力，这表明初级免疫反应的其他多余成分对于持久免疫反应很重要防止不断进化的病原体。我们的结果提供了 S 特异性记忆 B 细胞库的全球图谱，并说明了驱动病毒逃逸的特性以及赋予针对新出现变异的稳健性。