Potent neutralizing RBD‐specific antibody cocktail against SARS‐CoV‐2 and its mutant
Lina Jia,
Yan‐Ping Liu,
Li‐Fei Tian,
Chao Xiong,
Xin Xu,
Honge Qu,
Weixi Xiong,
Dong Zhou,
Feng Wang,
Zheng Liu,
Xiao‐Xue Yan,
Wenqing Xu,
Lin Tang
Affiliations
Lina Jia
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
Yan‐Ping Liu
National Laboratory of Biomacromolecules Chinese Academy of Sciences (CAS) Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences Beijing China
Li‐Fei Tian
National Laboratory of Biomacromolecules Chinese Academy of Sciences (CAS) Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences Beijing China
Chao Xiong
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
Xin Xu
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
Honge Qu
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
Weixi Xiong
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
Dong Zhou
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
Feng Wang
Wuxi Biortus Biosciences Co. Ltd. Jiangyin China
Zheng Liu
School of life and health Kobilka Institute of Innovative Drug Discovery the Chinese University of Hong Kong Shenzhen China
Xiao‐Xue Yan
National Laboratory of Biomacromolecules Chinese Academy of Sciences (CAS) Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences Beijing China
Wenqing Xu
National Laboratory of Biomacromolecules Chinese Academy of Sciences (CAS) Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences Beijing China
Lin Tang
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
Abstract 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‐RBDV367F 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.
