SARS-CoV-2 Omicron boosting induces de novo B cell response in humans
SARS-CoV-2 Omicron boosting induces de novo B cell response in humans
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DOI：
10.1038/s41586-023-06025-4
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发表时间：
2023-04-03
期刊：
影响因子：
64.8
通讯作者：
Ellebedy, Ali H.
中科院分区：
文献类型：
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作者：
Alsoussi, Wafaa B.;Malladi, Sameer Kumar;Ellebedy, Ali H.
最初的两剂SARS-CoV-2 mRNA疫苗系列在人类中具有强烈的免疫原性，但高感染性变体的出现需要额外的剂量和针对新变体的疫苗的开发（1-4）。人类SARS-CoV-2加强免疫主要招募预先存在的记忆B细胞（5-9）。然而，尚不清楚额外剂量是否诱导生发中心反应，由此重新接合的B细胞可以进一步成熟，以及变体衍生的疫苗是否可以引起对变体特异性表位的应答。在这里，我们表明，加强与mRNA疫苗对原来的单价SARS-CoV-2 mRNA疫苗或二价B.1.351和B.1.617.2（β/δ）mRNA疫苗诱导强大的尖峰特异性生发中心B细胞在人类中的反应。生发中心反应持续至少8周，导致明显更多的突变抗原特异性骨髓浆细胞和记忆B细胞隔室。来自记忆B细胞的刺突结合单克隆抗体主要识别原始SARS-CoV-2刺突蛋白，二价β/Delta疫苗或基于Omicron BA.1的单价疫苗。尽管如此，使用更有针对性的分选方法，我们从接受mRNA-1273.529加强剂的个体中分离出识别BA.1刺突蛋白但不识别原始SARS-CoV-2刺突蛋白的单克隆抗体;这些抗体突变较少，并识别刺突蛋白内的新表位，表明它们起源于幼稚B细胞。因此，SARS-CoV-2在人体中的加强免疫诱导了强有力的生发中心B细胞应答，并且可以产生靶向变体特异性表位的从头B细胞应答。
The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses and the development of vaccines aimed at the new variants(1-4). SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells(5-9). However, it remains unclear whether the additional doses induce germinal centre reactions whereby re-engaged B cells can further mature, and whether variant-derived vaccines can elicit responses to variant-specific epitopes. Here we show that boosting with an mRNA vaccine against the original monovalent SARS-CoV-2 mRNA vaccine or the bivalent B.1.351 and B.1.617.2 (Beta/Delta) mRNA vaccine induced robust spike-specific germinal centre B cell responses in humans. The germinal centre response persisted for at least eight weeks, leading to significantly more mutated antigen-specific bone marrow plasma cell and memory B cell compartments. Spike-binding monoclonal antibodies derived from memory B cells isolated from individuals boosted with either the original SARS-CoV-2 spike protein, bivalent Beta/Delta vaccine or a monovalent Omicron BA.1-based vaccine predominantly recognized the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted sorting approach, we isolated monoclonal antibodies that recognized the BA.1 spike protein but not the original SARS-CoV-2 spike protein from individuals who received the mRNA-1273.529 booster; these antibodies were less mutated and recognized novel epitopes within the spike protein, suggesting that they originated from naive B cells. Thus, SARS-CoV-2 booster immunizations in humans induce robust germinal centre B cell responses and can generate de novo B cell responses targeting variant-specific epitopes.