Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

First Author:  Fagre et al. 

Journal/preprint name: bioRxiv 

Paper DOI10.1101/2020.09.25.313601 

Tags: Neutralising antibodies, animal model. 

Summary

A panel of human monoclonal antibodies (mAbs) against the SARS-CoV-2 receptor binding domain (RBD) were identified using a yeast display library. These mAbs were able to neutralize the virus in vitro and the lead candidate was able to reduce viral load in Syrian hamsters under SARS-CoV-2 challenge, as well as improve lung pathology and reduce monocyte infiltration. This compound therefore has potential as a therapy to be used for COVID-19 patients. 

Research Highlights

  1.  A human mAb library displayed on yeast was used to identify a panel of mAbs against the SARS-CoV-2 RBD region. A series of assays such as MACS and FACS using recombinant SARS-CoV-2 RBD and competition ELISA with ACE2 were used to identify the most potent mAb candidates. 

  1. The most potent mAbAvGn-B, efficiently blocked RBD-ACE2 binding with an IC50 value of 2.2 nM. In vitroAvGn-B also showed 100% cell death protection against SARS-CoV-2. 

  1. AvGn-B was administered to Syrian hamsters on day 2 of SARS-CoV-2 infection. There was a significant reduction in lung viral load compared to the untreated group. However, there was no significant difference between lung viral load in the mice treated with AvGn-B and the isotype antibody control (IgG).  

  1. Pulmonary pathology was decreased in the AvGn-B treated group, as well as a reduction in inflammatory cell infiltrates in the pulmonary parenchyma of the AvGn-B high dose group. 

  1. The untreated group and IgG isotype control group had higher macrophage infiltration within the lungs seen by immunofluorescence, which was reduced dose-dependently by AvGn-B treatment.  

Impact for COVID-19 research:  

If this mAb is successful, it could be used as a treatment for COVID-19 patients; there are currently very limited treatment options for those with severe COVID-19. 

Methodologies: 

  • Study Type: In vitro & in vivo.  

  • Important cell lines/viral models used: Vero E6 cells. 

  • Key Techniques: In vitro neutralisation assay, competition ELISA (SARS-CoV-2 RBD, ACE2), lung histopathology, immunofluorescence. 

Limitations: 

  • No improvement of animal weight loss with AvGn-B treatment. 

  • No difference in viral load in the animals treated with AvGn-B compared to those treated with the isotype control.