tetano
Editor, Senior Moderator
Cell Discov
. 2021 Jul 27;7(1):57.
doi: 10.1038/s41421-021-00295-w.
Screening of potent neutralizing antibodies against SARS-CoV-2 using convalescent patients-derived phage-display libraries
Yongbing Pan[SUP] #[/SUP][SUP] 1 [/SUP], Jianhui Du[SUP] #[/SUP][SUP] 1 [/SUP], Jia Liu[SUP] #[/SUP][SUP] 2 [/SUP], Hai Wu[SUP] #[/SUP][SUP] 3 4 [/SUP], Fang Gui[SUP] 1 [/SUP], Nan Zhang[SUP] 1 [/SUP], Xiaojie Deng[SUP] 1 [/SUP], Gang Song[SUP] 1 [/SUP], Yufeng Li[SUP] 2 [/SUP], Jia Lu[SUP] 1 [/SUP], Xiaoli Wu[SUP] 1 [/SUP], ShanShan Zhan[SUP] 1 [/SUP], Zhaofei Jing[SUP] 1 [/SUP], Jiong Wang[SUP] 1 [/SUP], Yimin Yang[SUP] 1 [/SUP], Jianbang Liu[SUP] 1 [/SUP], Ying Chen[SUP] 1 [/SUP], Qin Chen[SUP] 1 [/SUP], Huanyu Zhang[SUP] 2 [/SUP], Hengrui Hu[SUP] 2 [/SUP], Kai Duan[SUP] 5 [/SUP], Manli Wang[SUP] 6 [/SUP], Qisheng Wang[SUP] 7 [/SUP], Xiaoming Yang[SUP] 8 9 [/SUP]
Affiliations
Abstract
As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (K[SUB]D[/SUB] = 4.76 nM for the S1 protein, IC[SUB]50[/SUB] = 6 ng/mL for pseudoviruses, and IC[SUB]50[/SUB] = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11-RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.
. 2021 Jul 27;7(1):57.
doi: 10.1038/s41421-021-00295-w.
Screening of potent neutralizing antibodies against SARS-CoV-2 using convalescent patients-derived phage-display libraries
Yongbing Pan[SUP] #[/SUP][SUP] 1 [/SUP], Jianhui Du[SUP] #[/SUP][SUP] 1 [/SUP], Jia Liu[SUP] #[/SUP][SUP] 2 [/SUP], Hai Wu[SUP] #[/SUP][SUP] 3 4 [/SUP], Fang Gui[SUP] 1 [/SUP], Nan Zhang[SUP] 1 [/SUP], Xiaojie Deng[SUP] 1 [/SUP], Gang Song[SUP] 1 [/SUP], Yufeng Li[SUP] 2 [/SUP], Jia Lu[SUP] 1 [/SUP], Xiaoli Wu[SUP] 1 [/SUP], ShanShan Zhan[SUP] 1 [/SUP], Zhaofei Jing[SUP] 1 [/SUP], Jiong Wang[SUP] 1 [/SUP], Yimin Yang[SUP] 1 [/SUP], Jianbang Liu[SUP] 1 [/SUP], Ying Chen[SUP] 1 [/SUP], Qin Chen[SUP] 1 [/SUP], Huanyu Zhang[SUP] 2 [/SUP], Hengrui Hu[SUP] 2 [/SUP], Kai Duan[SUP] 5 [/SUP], Manli Wang[SUP] 6 [/SUP], Qisheng Wang[SUP] 7 [/SUP], Xiaoming Yang[SUP] 8 9 [/SUP]
Affiliations
- PMID: 34315862
- DOI: 10.1038/s41421-021-00295-w
Abstract
As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (K[SUB]D[/SUB] = 4.76 nM for the S1 protein, IC[SUB]50[/SUB] = 6 ng/mL for pseudoviruses, and IC[SUB]50[/SUB] = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11-RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.