Extremely potent human monoclonal antibodies from convalescent Covid-19 patients

Author:

Andreano EmanueleORCID,Nicastri EmanueleORCID,Paciello Ida,Pileri PieroORCID,Manganaro Noemi,Piccini Giulia,Manenti Alessandro,Pantano Elisa,Kabanova Anna,Troisi Marco,Vacca Fabiola,Cardamone Dario,De Santi Concetta,Benincasa Linda,Agrati Chiara,Capobianchi Maria Rosaria,Castilletti Concetta,Emiliozzi Arianna,Fabbiani Massimiliano,Montagnani Francesca,Depau Lorenzo,Brunetti Jlenia,Bracci Luisa,Montomoli Emanuele,Sala Claudia,Ippolito Giuseppe,Rappuoli Rino

Abstract

SUMMARYHuman 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 Covid-19 pandemic. By single cell sorting 4277 SARS-CoV-2 spike protein specific memory B cells from 14 Covid-19 survivors, 453 neutralizing antibodies were identified and 220 of them were expressed as IgG. Up to 65,9% of monoclonals neutralized the wild type virus at a concentration of >500 ng/mL, 23,6% neutralized the virus in the range of 100 - 500 ng/mL and 9,1% had a neutralization potency in the range of 10 - 100 ng/mL. Only 1,4% neutralized the authentic virus with a potency of 1-10 ng/mL. We found that the most potent neutralizing antibodies are extremely rare and recognize the RBD, followed in potency by antibodies that recognize the S1 domain, the S-protein trimeric structure and the S2 subunit. The three most potent monoclonal antibodies identified were able to neutralize the wild type and D614G mutant viruses with less than 10 ng/mL and are good candidates for the development of prophylactic and therapeutic tools against SARS-CoV-2.One Sentence SummaryExtremely potent neutralizing human monoclonal antibodies isolated from Covid-19 convalescent patients for prophylactic and therapeutic interventions.

Publisher

Cold Spring Harbor Laboratory

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