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

Abstract

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.

• Authors: Yan Lou, Wenxiang Zhao, Haitao Wei, Min Chu, Ruihua Chao, Hangping Yao, Junwei Su, Yanan Li, Xiulan Li, Yu Cao, Yanyan Feng, Ping Wang, Yongyang Xia, Yushuan Shang, Fengping Li, Pingju Ge, Xinglin Zhang, Wenjing Gao, Gaojie Song, Bing Du, Tingbo Liang, Yunqing Qiu, Mingyao Liu
• Journal: Biotechnology journal (Biotechnol J) Vol. 16 Issue 11 Pg. e2100207 (Nov 2021) ISSN: 1860-7314 [Electronic] Germany
• PMID: 34379353 (Publication Type: Journal Article)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2

Topics

• Antibodies, Neutralizing
• Antibodies, Viral (immunology)
• COVID-19 (therapy)
• Humans
• Immunization, Passive
• Pandemics
• SARS-CoV-2 (genetics)
• Spike Glycoprotein, Coronavirus (genetics, immunology)
• COVID-19 Serotherapy