Understanding immune responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses following Omicron/BA.1 infection in mRNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation (SHM) and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells (MBCs). BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit, which is highly conserved across SARS-CoV-2 variants of concern (VOCs), and toward the antigenically variable receptor binding domain (RBD). A large proportion of RBD-directed neutralizing antibodies isolated from BA.1 breakthrough infection donors displayed convergent sequence features and broadly recognized SARS-CoV-2 VOCs. Together, these findings provide insights into the role of pre-existing immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure.

中文翻译：

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回忆 Omicron BA.1 突破性感染后已有的交叉反应性 B 细胞记忆

了解严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 突破性感染后的免疫反应将有助于开发下一代疫苗。在这里，我们分析了接种 mRNA 的供体中 Omicron/BA.1 感染后的尖峰 (S) 特异性 B 细胞反应。急性抗体反应的特点是高水平的体细胞超突变 (SHM) 和对祖先 SARS-CoV-2 毒株的识别偏向，表明疫苗诱导的记忆 B 细胞 (MBC) 的早期激活。BA.1 突破性感染导致 B 细胞免疫优势等级从 S2 亚基发生转变，S2 亚基在 SARS-CoV-2 相关变体 (VOC) 中高度保守，并向抗原可变受体结合域 (RBD) 转变。从 BA 中分离出大部分针对 RBD 的中和抗体。1 个突破性感染供体显示出趋同的序列特征和广泛认可的 SARS-CoV-2 VOC。总之，这些发现提供了对预先存在的免疫力在塑造 B 细胞对异源 SARS-CoV-2 变异暴露的反应中的作用的见解。