A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters

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. 

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

3. 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).  

4. 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. 

5. 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.