State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Nat Commun. 2024 Aug 31;15(1):7585. doi: 10.1038/s41467-024-51770-3.
Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.
SARS-CoV-2 的持续进化产生了变异株，以挑战感染和接种疫苗所建立的抗体免疫。人群免疫力与病毒变异的产生之间存在关联早已被提出，但其分子基础仍知之甚少。在这里，我们确定了一类由共用 VL6-57 轻链定义的 SARS-CoV-2 中和公共抗体。尽管使用了不同基因型的重链，但这些公共抗体之间观察到了趋同的 HCDR3 重排，与胚系 VL6-57 LCDRs 合作，以针对由 RBD 残基 S371-S373-S375 定义的趋同表位。抗体库分析确定，这类 VL6-57 抗体存在于 SARS-CoV-2 未感染的个体中，并在大多数 COVID-19 患者中克隆扩增。我们证实，S371、S373 和 S375 处的奥密克戎特异性取代介导了 VL6-57 类抗体的逃逸。这些发现支持了这一类公共抗体构成了一种潜在的免疫压力，促进了奥密克戎变体中 S371L/F-S373P-S375F 的引入。该结果提供了进一步的分子证据，支持 SARS-CoV-2 的抗原进化是由抗体介导的人群免疫驱动的。
