iScience
Volume 25, Issue 12, 22 December 2022, 105596
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Article
Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models

https://doi.org/10.1016/j.isci.2022.105596Get rights and content
Under a Creative Commons license
open access

Highlights

  • Neutralizing antibodies were produced from COVID-19 convalescent peripheral B cells

  • The structure of the antibodies and their efficacy against variants were demonstrated

  • N297A modification was introduced to prevent antibody-dependent enhancement

  • Antibodies showed in vivo treatment effects in both hamsters and macaques

Summary

The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical antibodies against viruses 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 prevent antibody-dependent enhancement, N297A modification was introduced. Our antibodies showed a reduction of lung viral RNAs by therapeutic administration in a hamster model. In addition, an antibody cocktail consisting of three antibodies was also administered therapeutically to a macaque model, which resulted 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.

Subject areas

Unology
immune response
virology

Data and code availability

The cryo-EM maps and atomic models have been deposited at the Electron Microscopy DataBank and the PDB with the accession codes listed in Table S3, and are publicly available as of the date of publication. Additional data needed to support the conclusion of this manuscript are included in the main text and supplementary materials. This paper does not report original code. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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