Extremely potent human monoclonal antibodies from COVID-19 convalescent patients
- PMID: 33667349
- PMCID: PMC7901298
- DOI: 10.1016/j.cell.2021.02.035
Extremely potent human monoclonal antibodies from COVID-19 convalescent patients
Abstract
Human monoclonal antibodies are safe, preventive, and therapeutic tools that can be rapidly developed to help restore the massive health and economic disruption caused by the coronavirus disease 2019 (COVID-19) pandemic. By single-cell sorting 4,277 SARS-CoV-2 spike protein-specific memory B cells from 14 COVID-19 survivors, 453 neutralizing antibodies were identified. The most potent neutralizing antibodies recognized the spike protein receptor-binding domain, followed in potency by antibodies that recognize the S1 domain, the spike protein trimer, and the S2 subunit. Only 1.4% of them neutralized the authentic virus with a potency of 1-10 ng/mL. The most potent monoclonal antibody, engineered to reduce the risk of antibody-dependent enhancement and prolong half-life, neutralized the authentic wild-type virus and emerging variants containing D614G, E484K, and N501Y substitutions. Prophylactic and therapeutic efficacy in the hamster model was observed at 0.25 and 4 mg/kg respectively in absence of Fc functions.
Keywords: COVID-19; Fc functions absence; SARS-CoV-2; emerging variants; monoclonal antibodies; prophylaxis; therapy.
Copyright © 2021 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests R.R. is an employee of GSK group of companies. E.A., A.K., D.C., C.D.S, I.P., N.M., E.P., P.P., C.S., M.T., F.V., and R.R. are listed as inventors of full-length human monoclonal antibodies described in Italian patent applications no. 102020000015754 filed on June 30, 2020 and no. 102020000018955 filed on August 3, 2020.
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References
-
- Aratani L. 2020. Jobless America: the coronavirus unemployment crisis in figures. The Guardian, May 28, 2020.https://www.theguardian.com/business/2020/may/28/jobless-america-unemplo...
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