Extremely potent human monoclonal antibodies from COVID-19 convalescent 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; Torres, Jonathan L.; Ozorowski, Gabriel; Benincasa, Linda; Jang, Hyesun; Di Genova, Cecilia; Depau, Lorenzo; Brunetti, Jlenia; Agrati, Chiara; Capobianchi, Maria Rosaria; Castilletti, Concetta; Emiliozzi, Arianna; Fabbiani, Massimiliano; Montagnani, Francesca; Bracci, Luisa; Sautto, Giuseppe; Ross, Ted M.; Montomoli, Emanuele; Temperton, Nigel; Ward, Andrew B.; 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 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.