Screening of potent neutralizing antibodies against SARS-CoV-2 using convalescent patients-derived phage-display libraries.
Yongbing PanJianhui DuJia LiuHai WuFang GuiNan ZhangXiaojie DengGang SongYufeng LiJia LuXiaoli WuShanShan ZhanZhaofei JingJiong WangYimin YangJianbang LiuYing ChenQin ChenHuanyu ZhangHengrui HuKai DuanMan-Li WangQisheng WangXiao Ming YangPublished in: Cell discovery (2021)
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 (KD = 4.76 nM for the S1 protein, IC50 = 6 ng/mL for pseudoviruses, and IC50 = 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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- end stage renal disease
- public health
- dengue virus
- newly diagnosed
- ejection fraction
- chronic kidney disease
- copy number
- wild type
- randomized controlled trial
- peritoneal dialysis
- genome wide
- physical activity
- skeletal muscle
- clinical trial
- single cell
- type diabetes
- small molecule
- cancer therapy
- patient reported
- zika virus
- climate change
- anti inflammatory
- open label
- transcription factor
- insulin resistance
- genome wide identification