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Potently neutralizing human antibodies that block SARS-CoV-2 receptor binding and protect animals.
- Source :
-
BioRxiv : the preprint server for biology [bioRxiv] 2020 May 22. Date of Electronic Publication: 2020 May 22. - Publication Year :
- 2020
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Abstract
- The COVID-19 pandemic is a major threat to global health for which there are only limited medical countermeasures, and we lack a thorough understanding of mechanisms of humoral immunity <superscript>1,2</superscript> . From a panel of monoclonal antibodies (mAbs) targeting the spike (S) glycoprotein isolated from the B cells of infected subjects, we identified several mAbs that exhibited potent neutralizing activity with IC <subscript>50</subscript> values as low as 0.9 or 15 ng/mL in pseudovirus or wild-type ( wt ) SARS-CoV-2 neutralization tests, respectively. The most potent mAbs fully block the receptor-binding domain of S (S <subscript>RBD</subscript> ) from interacting with human ACE2. Competition-binding, structural, and functional studies allowed clustering of the mAbs into defined classes recognizing distinct epitopes within major antigenic sites on the S <subscript>RBD</subscript> . Electron microscopy studies revealed that these mAbs recognize distinct conformational states of trimeric S protein. Potent neutralizing mAbs recognizing unique sites, COV2-2196 and COV2-2130, bound simultaneously to S and synergistically neutralized authentic SARS-CoV-2 virus. In two murine models of SARS-CoV-2 infection, passive transfer of either COV2-2916 or COV2-2130 alone or a combination of both mAbs protected mice from severe weight loss and reduced viral burden and inflammation in the lung. These results identify protective epitopes on the S <subscript>RBD</subscript> and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutic cocktails.
Details
- Language :
- English
- Database :
- MEDLINE
- Journal :
- BioRxiv : the preprint server for biology
- Accession number :
- 32511409
- Full Text :
- https://doi.org/10.1101/2020.05.22.111005