Extremely potent human monoclonal antibodies from convalescent Covid-19 patients

Andreano, Emanuele; Nicastri, Emanuele; Paciello, Ida; Pileri, Piero; 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

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 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 Summary Extremely potent neutralizing human monoclonal antibodies isolated from Covid-19 convalescent patients for prophylactic and therapeutic interventions.