Extremely potent human monoclonal antibodies from COVID-19 convalescent patients

Emanuele Andreano, Emanuele Nicastri, Ida Paciello, Piero Pileri, Noemi Manganaro, Giulia Piccini, Alessandro Manenti, Elisa Pantano, Anna Kabanova, Marco Troisi, Fabiola Vacca, Dario Cardamone, Concetta De Santi, Jonathan L. Torres, Gabriel Ozorowski, Linda Benincasa, Hyesun Jang, Cecilia Di Genova, Lorenzo Depau, Jlenia BrunettiChiara Agrati, Maria Rosaria Capobianchi, Concetta Castilletti, Arianna Emiliozzi, Massimiliano Fabbiani, Francesca Montagnani, Luisa Bracci, Giuseppe Sautto, Ted M. Ross, Emanuele Montomoli, Nigel Temperton, Andrew B. Ward, Claudia Sala, Giuseppe Ippolito, Rino Rappuoli

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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. Extremely potent neutralizing human monoclonal antibodies, though rare, are isolated from COVID-19 convalescent patients and suitable for prophylactic and therapeutic interventions of wild-type SARS-CoV-2 as well as emerging variants.
Original languageEnglish
JournalCell
Volume184
Issue number7
DOIs
StatePublished - 1 Apr 2021

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