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Your Position: > Insights > Isolated antibodies in SARS-CoV-2 infected patients have potential to treat COVID-19
Isolated antibodies in SARS-CoV-2 infected patients have potential to treat COVID-19
Release time: 2020-04-07 Source: ACRO Read: 11436

The pandemic caused by emerging coronavirus SARS-CoV-2 presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. Scientists working to quell the COVID-19 pandemic think it will be possible to isolate monoclonal antibodies (mAbs) in SARS-CoV-2 infected patients and identify which antibodies are the most potent in quashing a coronavirus infection, and then make vast quantities of identical copies of these proteins synthetically to treat COVID-19. 


Recently a team of Chinese scientists published a research paper1 on bioRxiv, the preprint server for Biology, reporting the isolation and characterization of mAbs derived from single B cells of eight SARS-CoV-2 infected individuals. The highlights of this study are summarized here:


1. Serial dilutions of plasma samples from eight SARS-CoV-2 infected subjects were analyzed for binding to RBDs from SARS-CoV-2, SARS-CoV and MERS-CoV. The plasma samples showed binding activity to SARS-CoV-2 RBD, while no cross-reactivity was detected against SARS-CoV RBD and MERS-CoV RBD. The results suggest that the RBD-based antibody response is viral species-specific (Fig 1).

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Fig 1. Analyses of plasma responses specific to SARS-CoV-2.


2. Flow cytometry was used to study SARS-CoV-2-specific B cell responses and identify B cells recognizing fluorescent-labeled RBD probes (Fig.2). They further isolated RBD-binding B cells into single cell suspension for cloning and obtained 206 mAbs that bound to SARS-CoV-2 RBD.


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Fig 2. Gating strategy for analysis and isolation of SARS-CoV-2 RBD-specific memory B cells.


3. They selected 18 antibody clones based on their distribution on the phylogenetic tree and detected their binding to SARS-CoV-2 RBD using surface plasmon resonance (SPR). The dissociation constants of the antibodies ranged from 10-8 to 10-9 M, while none of the antibodies demonstrated cross-binding with SARS-CoV RBD and MERS-CoV RBD (Fig 3). 

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Fig 3. Binding kinetics of selected mAbs with SARS-CoV-2 RBD, SARS-CoV RBD and MERS-CoV RBD measured by SPR.


4. They measured the 18 antibodies for competition with ACE2 for binding to the SARS-CoV-2 RBD.  While many antibodies showed strong binding to ACE2, they had only limited competing power with ACE2, suggesting binding affinity is not predictive of ACE2 competing capacity (Fig 4).

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Fig 4. Antibody and ACE2 competition for binding to SARS-CoV-2 RBD measured by SPR.


5. They studied antibody neutralizing activities against pseudoviruses bearing the Spike protein of SARS-CoV-2. The neutralizing activities correlated well with the ACE2 competing capacity and in particular, the most potent antibodies (299 P2C-1F11 and P2B-2F6) out-competed ACE2 with close to 100% efficiency, indicating that blocking the RBD and ACE2 interaction is a useful surrogate for antibody neutralization (Fig 5).

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Fig 5 Antibody neutralization analyzed by pseudovirus.


The diverse and potent neutralizing antibodies identified in this study are promising candidates for prophylactic and therapeutic SARS-CoV-2 interventions. Currently the scientists are conducting pre-clinical studies in hoping to translate the identified mAbs into anti-COVID-19 drugs. 


As the research paper suggested, blocking the RBD and ACE2 interaction is a useful surrogate for antibody neutralization. However, the low-throughput of SPR instruments limits the screening of large amounts of candidate drugs including neutralizing antibodies and small molecules. To solve this problem, ACROBiosystems develops ‘SARS-CoV-2 Inhibitor Screening Kit’, which employs colorimetric ELISA platform to measure the inhibitory effect of potential inhibitors on blocking the binding between immobilized SARS-CoV-2 S protein RBD and in-house developed biotinylated human ACE2 protein (Fig 6). This product would enable researchers to conduct high-throughput screening of SARS-CoV-2 inhibitors and speed up the development of therapeutics against COVID-19.  




Reference (click below to download the PDF version of the literature ):

1. Potent human neutralizing antibodies elicited by SARS-CoV-2 infection.


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