Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province 518112, China.
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province 518112, China; Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen, Guangdong Province 518112, China.
Cell Rep. 2022 Sep 13;40(11):111335. doi: 10.1016/j.celrep.2022.111335. Epub 2022 Aug 23.
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.
虽然已经鉴定和充分表征了数千种抗 SARS-CoV-2 单克隆中和抗体（nAbs），但这些 nAbs 在病毒感染过程中的一些关键事件仍不清楚。我们使用深度测序技术，探索了从先前分离出强效且广谱 nAb P2C-1F11（Brii-196 的原始版本）的 SARS-CoV-2 感染供体的抗体库的动态。进一步的分析表明，在早期感染中，一些 SARS-CoV-2 特异性抗体迅速克隆扩增。对 P2C-1F11 谱系抗体的纵向追踪表明，这些精英 nAbs 较为罕见。通过序列比对、结构建模和基于位点突变的活性分析，我们证明重链中的关键取代 F27I 对 P2C-1F11 样抗体的成熟有重要贡献。总的来说，我们的研究结果阐明了 P2C-1F11 的发育过程和成熟途径，为设计新型免疫原以诱导针对 SARS-CoV-2 感染的更有效 nAbs 提供了一些重要信息。
