Cross-neutralization of RBD mutant strains of SARS-CoV-2 by convalescent patient derived antibodies

被引:7
作者
Lou, Yan [1 ]
Zhao, Wenxiang [2 ,3 ,4 ]
Wei, Haitao [4 ]
Chu, Min [4 ]
Chao, Ruihua [2 ,3 ]
Yao, Hangping [1 ]
Su, Junwei [1 ]
Li, Yanan [4 ]
Li, Xiulan [4 ]
Cao, Yu [4 ]
Feng, Yanyan [4 ]
Wang, Ping [4 ]
Xia, Yongyang [4 ]
Shang, Yushuan [4 ]
Li, Fengping [4 ]
Ge, Pingju [5 ]
Zhang, Xinglin [5 ]
Gao, Wenjing [5 ]
Song, Gaojie [2 ,3 ]
Du, Bing [2 ,3 ]
Liang, Tingbo [1 ]
Qiu, Yunqing [1 ]
Liu, Mingyao [2 ,3 ]
机构
[1] Zhejiang Univ, Affiliated Hosp 1, Key Lab Drug Evaluat & Clin Res Zhejiang Prov, State Key Lab Diag & Treatment Infect Dis,Sch Med, 79 Qingchun Rd, Hangzhou 310003, Peoples R China
[2] East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China
[3] East China Normal Univ, Sch Life Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China
[4] SymRay Biopharma LLC, Shanghai, Peoples R China
[5] Acrobiosyst Inc, Beijing, Peoples R China
基金
国家重点研发计划;
关键词
neutralizing antibodies; patient-derived antibody libraries; SARS-CoV-2; Spike protein; SARS CORONAVIRUS; SPIKE PROTEIN; BINDING; MUTATIONS; LIBRARIES;
D O I
10.1002/biot.202100207
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Background The emergence of COVID-19 pandemic resulted in an urgent need for the development of therapeutic interventions. Of which, neutralizing antibodies play a crucial role in the prevention and resolution of viral infection. Methods We generated antibody libraries from 18 different COVID-19 recovered patients and screened neutralizing antibodies to SARS-CoV-2 and its mutants. After 3 rounds of panning, 456 positive phage clones were obtained with high affinity to RBD (receptor binding domain). Clones were then reconstituted into whole human IgG for epitope binning assay and all 19 IgG were classified into 6 different epitope groups or Bins. Results Although all antibodies were found to bind RBD, the antibodies in Bin2 had superior inhibitory ability of the interaction between spike protein and angiotensin converting enzyme 2 receptor (ACE2). Most importantly, the antibodies from Bin2 showed stronger binding affinity or ability to mutant RBDs (N501Y, W463R, R408I, N354D, V367F, and N354D/D364Y) derived from different SARS-CoV-2 strains as well, suggesting the great potential of these antibodies in preventing infection of SARS-CoV-2 and its mutations. Furthermore, such neutralizing antibodies strongly restricted the binding of RBD to hACE2 overexpressed 293T cells. Consistently, these antibodies effectively neutralized wildtype and more transmissible mutant pseudovirus entry into hACE2 overexpressed 293T cells. In Vero-E6 cells, one of these antibodies can even block the entry of live SARS-CoV-2 into cells at 12.5 nM. Conclusions These results indicate that the neutralizing human antibodies from the patient-derived antibody libraries have the potential to fight SARS-CoV-2 and its mutants in this global pandemic.
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页数:14
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