Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Adimab LLC, Lebanon, NH, 03766, USA.
Nat Commun. 2023 Apr 19;14(1):2249. doi: 10.1038/s41467-023-37972-1.
Vaccination of SARS-CoV-2 convalescent individuals generates broad and potent antibody responses. Here, we isolate 459 spike-specific monoclonal antibodies (mAbs) from two individuals who were infected with the index variant of SARS-CoV-2 and later boosted with mRNA-1273. We characterize mAb genetic features by sequence assignments to the donors' personal immunoglobulin genotypes and assess antibody neutralizing activities against index SARS-CoV-2, Beta, Delta, and Omicron variants. The mAbs used a broad range of immunoglobulin heavy chain (IGH) V genes in the response to all sub-determinants of the spike examined, with similar characteristics observed in both donors. IGH repertoire sequencing and B cell lineage tracing at longitudinal time points reveals extensive evolution of SARS-CoV-2 spike-binding antibodies from acute infection until vaccination five months later. These results demonstrate that highly polyclonal repertoires of affinity-matured memory B cells are efficiently recalled by vaccination, providing a basis for the potent antibody responses observed in convalescent persons following vaccination.
SARS-CoV-2 康复个体的疫苗接种会产生广泛而有效的抗体反应。在这里，我们从两名感染了 SARS-CoV-2 原始变体并随后接种 mRNA-1273 的个体中分离出 459 种刺突特异性单克隆抗体（mAb）。我们通过将 mAb 序列分配给供体的个人免疫球蛋白基因型来表征 mAb 的遗传特征，并评估针对原始 SARS-CoV-2、Beta、Delta 和 Omicron 变体的抗体中和活性。在对所有检查的刺突亚决定簇的反应中，mAb 使用了广泛的免疫球蛋白重链（IGH）V 基因，在两个供体中观察到相似的特征。IGH 库测序和纵向时间点的 B 细胞谱系追踪显示，从急性感染到五个月后接种疫苗期间，SARS-CoV-2 刺突结合抗体经历了广泛的进化。这些结果表明，高效价的亲和力成熟记忆 B 细胞多克隆库可通过疫苗接种有效召回，为康复个体接种疫苗后观察到的强烈抗体反应提供了基础。
