Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models

The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical antibodies against vi-ruses that are acquiring mutations. In this study, we created 494 monoclonal antibodies from patients with COVID-19-convalescent, and identified antibodies that exhibited the comparable neutralizing ability to clinically used antibodies in the neutralization assay using pseudovirus and authentic virus including variants of concerns. These antibodies have different profiles against various mutations, which were confirmed by cell-based assay and cryo-electron microscopy. To pre-vent antibody-dependent enhancement, N297A modification was introduced. Our antibodies showed a reduction of lung viral RNAs by therapeutic administra-tion in a hamster model. In addition, an antibody cocktail consisting of three antibodies was also administered therapeutically to a macaque model, which re-sulted in reduced viral titers of swabs and lungs and reduced lung tissue damage scores. These results showed that our antibodies have sufficient antiviral activity as therapeutic candidates.

Automated summary

Therapeutic neutralizing antibodies against SARS-CoV-2 infection have been highly effective. In this study, monoclonal antibodies were created from COVID-19 convalescent patients and antibodies that exhibited comparable neutralizing ability to clinically used antibodies were identified. These antibodies have shown antiviral activity against various mutations and a modification was introduced to prevent antibody-dependent enhancement. Therapeutic administration of these antibodies in animal models resulted in reduction of viral load and tissue damage.