Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection.

Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection.
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Omicron BA.1 突破性感染后,回想起先前存在的交叉反应 B 细胞记忆。

DOI:
10.1126/sciimmunol.abq3511
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发表时间:
2022-07-29
期刊:
影响因子:
24.8
通讯作者:
--
中科院分区:
医学1区
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了解严重急性呼吸综合征冠状病毒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Omicron/BA后的spike (S)特异性B细胞反应。1感染的mrna接种供体。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菌株的识别,提示疫苗诱导的记忆B细胞(MBCs)的早期激活。BA.1突破感染诱导B细胞免疫优势结构从S2亚基(在SARS-CoV-2关注变体(VOCs)中高度保守)向抗原可变受体结合域(RBD)转移。从BA.1突破性感染供体中分离的rbd定向中和抗体大部分表现出序列趋同特征和广泛识别的SARS-CoV-2 VOCs。总之,这些发现为预先存在的免疫在形成B细胞对异源SARS-CoV-2变体暴露的反应中的作用提供了见解。ba - 1突破感染激活预先存在的记忆B细胞,对SARS-CoV-2变体具有广泛的活性。
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. BA.1 breakthrough infection activates pre-existing memory B cells with broad activity against SARS-CoV-2 variants.
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