Jia Lina, Liu Yan-Ping, Tian Li-Fei, Xiong Chao, Xu Xin, Qu Honge, Xiong Weixi, Zhou Dong, Wang Feng, Liu Zheng, Yan Xiao-Xue, Xu Wenqing, Tang Lin
Department of Neurology State Key Lab of Biotherapy and Cancer center West China Hospital Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu Sichuan China.
National Laboratory of Biomacromolecules Chinese Academy of Sciences (CAS) Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences Beijing China.
MedComm (2020). 2021 Jun 24;2(3):442-452. doi: 10.1002/mco2.79. eCollection 2021 Sep.
The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants has posed a serious global public health emergency. Therapeutic interventions or vaccines are urgently needed to treat and prevent the further dissemination of this contagious virus. This study described the identification of neutralizing receptor-binding domain (RBD)-specific antibodies from mice through vaccination with a recombinant SARS-CoV-2 RBD. RBD-targeted monoclonal antibodies (mAbs) with distinct function and epitope recognition were selected to understand SARS-CoV-2 neutralization. High-affinity RBD-specific antibodies exhibited high potency in neutralizing both live and pseudotype SARS-CoV-2 viruses and the SARS-CoV-2 pseudovirus particle containing the spike protein S-RBD mutant (SARS-CoV-2(V367F)). These results demonstrated that these antibodies recognize four distinct groups (I-IV) of epitopes on the RBD and that mAbs targeting group I epitope can be used in combination with mAbs recognizing groups II and/or IV epitope to make mAb cocktails against SARS-CoV-2 and its mutants. Moreover, structural characterization reveals that groups I, III, and IV epitopes are closely located to an RBD hotspot. The identification of RBD-specific antibodies and cocktails may provide an effective therapeutic and prophylactic intervention against SARS-CoV-2 and its isolates.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）及其变体引起的持续大流行已构成严重的全球公共卫生紧急事件。迫切需要治疗性干预措施或疫苗来治疗和预防这种传染性病毒的进一步传播。本研究描述了通过用重组SARS-CoV-2受体结合域（RBD）进行疫苗接种从小鼠中鉴定中和性RBD特异性抗体。选择具有不同功能和表位识别的靶向RBD的单克隆抗体（mAb）以了解SARS-CoV-2中和作用。高亲和力RBD特异性抗体在中和活的和假型SARS-CoV-2病毒以及含有刺突蛋白S-RBD突变体（SARS-CoV-2(V367F)）的SARS-CoV-2假病毒颗粒方面表现出高效力。这些结果表明，这些抗体识别RBD上四个不同的表位组（I-IV），并且靶向I组表位的mAb可与识别II组和/或IV组表位的mAb联合使用，以制备针对SARS-CoV-2及其突变体的mAb混合物。此外，结构表征显示I、III和IV组表位紧密位于RBD热点附近。RBD特异性抗体和混合物的鉴定可能为针对SARS-CoV-2及其分离株提供有效的治疗和预防干预措施。
