A key F27I substitution within HCDR1 facilitates the rapid maturation of P2C-1F11-like neutralizing antibodies in a SARS-CoV-2-infected donor.
A key F27I substitution within HCDR1 facilitates the rapid maturation of P2C-1F11-like neutralizing antibodies in a SARS-CoV-2-infected donor.
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DOI：
10.1016/j.celrep.2022.111335
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发表时间：
2022-09-13
期刊：
影响因子：
8.8
通讯作者：
Zhang, Zheng
中科院分区：
文献类型：
--
作者：
Wang, Miao;Fan, Qing;Zhou, Bing;Ye, Haocheng;Shen, Senlin;Yu, Jiazhen;Cheng, Lin;Ge, Xiangyang;Ju, Bin;Zhang, Zheng
尽管目前已鉴定和鉴定了数千种抗SARS-CoV-2的中和抗体，但在病毒感染过程中这些中和抗体的发展过程中的一些关键事件仍不清楚。通过深度测序，我们探索了一名感染SARS-CoV-2的捐赠者的抗体库的动态变化，从该捐赠者中分离出了强大而广泛的NAB P2C-1F11(Brii-196的亲本版本)。进一步分析表明，在早期感染中，一些SARS-CoV-2特异性抗体可以迅速克隆性扩增。对P2C-1F11谱系抗体的纵向追踪表明，这些精英NAB是罕见的。通过序列比对、结构建模和基于定点突变的生物活性分析，我们证明了重链上的关键替换F27I对类P2C-1F11抗体的成熟有重要作用。总之，我们的发现阐明了P2C-1F11的发育过程和成熟途径，为设计新的免疫原以诱导更有效的抗SARS-CoV-2抗体提供了重要信息。中和抗体对于预防和治疗SARS-CoV-2感染是必不可少的。Wang等人。证实了新冠肺炎患者在整个疾病过程中抗体库的戏剧性变化，并揭示了HCDR1内的一个关键突变，导致了类似P2C-1F11的NAB的发展。
Although thousands of anti-SARS-CoV-2 monoclonal neutralizing antibodies (nAbs) have been identified and well characterized, some crucial events in the development of these nAbs during viral infection remain unclear. Using deep sequencing, we explore the dynamics of antibody repertoire in a SARS-CoV-2-infected donor, from whom the potent and broad nAb P2C-1F11 (the parent version of Brii-196) was previously isolated. Further analysis shows a rapid clonal expansion of some SARS-CoV-2-specific antibodies in early infection. Longitudinal tracing of P2C-1F11 lineage antibodies reveals that these elite nAbs were rare. Using sequence alignment, structure modeling, and bioactivity analysis based on site-mutated assay, we demonstrate that a key substitution F27I in heavy chain contributes significantly to the maturation of P2C-1F11-like antibodies. Overall, our findings elucidate the developmental process and maturation pathway of P2C-1F11, providing some important information for the design of novel immunogens to elicit more potent nAbs against SARS-CoV-2 infection. Neutralizing antibodies are essential for the prevention and treatment of SARS-CoV-2 infection. Wang et al. demonstrate dramatic changes of antibody repertoire in a COVID-19 patient throughout the whole disease process and reveal a key mutation within HCDR1 for the development of P2C-1F11-like nAbs.
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