Potently neutralizing human antibodies that block SARS-CoV-2 receptor binding and protect animals.

BioRxiv : the Preprint Server for Biology
Seth J ZostJames E Crowe

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 1,2 . 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 50 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 RBD ) 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 RBD . 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...Continue Reading

Citations

Jul 22, 2020·The Journal of Experimental Medicine·Fabian SchmidtPaul D Bieniasz
Oct 20, 2020·Emerging Microbes & Infections·Raveen RathnasingheMelissa B Uccellini
Oct 21, 2020·Nature Reviews. Nephrology·Luca PericoGiuseppe Remuzzi
Nov 15, 2020·Viruses·Lin Wang, Ye Xiang
Jun 18, 2021·Frontiers in Molecular Biosciences·Arnaud John Kombe KombeTengchuan Jin

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Methods Mentioned

BETA
ELISA
biosensors
competition binding
biolayer interferometry
electron microscopy

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