| Autor: |
Zost SJ, Gilchuk P, Case JB, Binshtein E, Chen RE, Reidy JX, Trivette A, Nargi RS, Sutton RE, Suryadevara N, Williamson LE, Chen EC, Jones T, Day S, Myers L, Hassan AO, Kafai NM, Winkler ES, Fox JM, Steinhardt JJ, Ren K, Loo YM, Kallewaard NL, Martinez DR, Schäfer A, Gralinski LE, Baric RS, Thackray LB, Diamond MS, Carnahan RH, Crowe JE |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2020 May 22. Date of Electronic Publication: 2020 May 22. |
| DOI: |
10.1101/2020.05.22.111005 |
| Abstrakt: |
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 weight loss and reduced viral burden and inflammation in the lung. These results identify protective epitopes on the S RBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutic cocktails. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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