Neutralization or enhancement of SARS-CoV-2 infection by a monoclonal antibody targeting a specific epitope in the spike receptor-binding domain

Neutralizing antibodies (NAbs) are believed to be promising prophylactic and therapeutic treatment against the coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we reported two mouse monoclonal antibodies 7 Eb-4G and 1Ba–3H th...

Full description

Saved in:
Bibliographic Details
Published in:Antiviral research 2022-04, Vol.200, p.105290-105290, Article 105290
Main Authors: Lai, Guan-Chun, Chao, Tai-Ling, Lin, Shiau-Yu, Kao, Han-Chieh, Tsai, Ya-Min, Lu, De-Chao, Chiang, Yi-Wei, Chang, Sui-Yuan, Chang, Shih-Chung
Format: Article
Language:English
Subjects:
ACE2
Animals
Antibodies, Monoclonal
Antibody-dependent enhancement
COVID-19
Epitopes
HEK293 Cells
Humans
Mice
Neutralizing antibody
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Spike receptor binding domain
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Neutralizing antibodies (NAbs) are believed to be promising prophylactic and therapeutic treatment against the coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we reported two mouse monoclonal antibodies 7 Eb-4G and 1Ba–3H that specifically recognized the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein without exhibiting cross-reactivity with the S proteins of SARS-CoV and MERS-CoV. The binding epitopes of 7 Eb-4G and 1Ba–3H were respectively located in the regions of residues 457–476 and 477–496 in the S protein. Only 1Ba–3H exhibited the neutralizing activity for preventing the pseudotyped lentivirus from binding to the angiotensin-converting enzyme 2 (ACE2)-transfected HEK293T cells. The competitive ELISA further showed that 1Ba–3H interfered with the binding between RBD and ACE2. Epitope mapping experiments demonstrated that a single alanine replacement at residues 480, 482, 484, 485, and 488–491 in the RBD abrogated 1Ba–3H binding. 1Ba–3H exhibited the neutralizing activity against the wild-type, Alpha, Delta, and Epsilon variants of SARS-CoV-2, but lost the neutralizing activity against Gamma variant in the plaque reduction assay. On the contrary, 1Ba–3H enhanced the cellular infection of Gamma variant in a dose-dependent manner. Our findings suggest that the antibody-dependent enhancement of infection mediated by the RBD-specific antibody for different SARS-CoV-2 variants must be considered while developing the NAb. •We developed two monoclonal antibodies 7Eb-4G and 1Ba–3H targeting the SARS-CoV-2 spike receptor binding domain.•1Ba–3H blocked the pseudotyped lentivirus binding to the ACE2-transfected HEK293T cells.•1Ba–3H exhibited the neutralizing potency against the wild-type, Alpha, Delta, and Epsilon variants of SARS-CoV-2.•1Ba–3H enhanced the infection of SARS-CoV-2 Gamma variant.
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2022.105290