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Potent neutralizing RBD-specific antibody cocktail against SARS-CoV-2 and its mutant. 2021

Lina Jia, and Yan-Ping Liu, and Li-Fei Tian, and Chao Xiong, and Xin Xu, and Honge Qu, and Weixi Xiong, and Dong Zhou, and Feng Wang, and Zheng Liu, and Xiao-Xue Yan, and Wenqing Xu, and 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.

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.

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