Cell . Extremely potent human monoclonal antibodies from COVID-19 convalescent patients

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. 2021 Feb 23;S0092-8674(21)00224-5.
doi: 10.1016/j.cell.2021.02.035. Online ahead of print.
Extremely potent human monoclonal antibodies from COVID-19 convalescent patients


Emanuele Andreano ¹ , Emanuele Nicastri ² , Ida Paciello ¹ , Piero Pileri ¹ , Noemi Manganaro ¹ , Giulia Piccini ³ , Alessandro Manenti ⁴ , Elisa Pantano ¹ , Anna Kabanova ⁵ , Marco Troisi ⁶ , Fabiola Vacca ⁶ , Dario Cardamone ⁷ , Concetta De Santi ¹ , Jonathan L Torres ⁸ , Gabriel Ozorowski ⁸ , Linda Benincasa ⁹ , Hyesun Jang ¹⁰ , Cecilia Di Genova ¹¹ , Lorenzo Depau ¹² , Jlenia Brunetti ¹² , Chiara Agrati ² , Maria Rosaria Capobianchi ² , Concetta Castilletti ² , Arianna Emiliozzi ¹³ , Massimiliano Fabbiani ¹⁴ , Francesca Montagnani ¹³ , Luisa Bracci ¹² , Giuseppe Sautto ¹⁰ , Ted M Ross ¹⁵ , Emanuele Montomoli ¹⁶ , Nigel Temperton ¹¹ , Andrew B Ward ⁸ , Claudia Sala ¹ , Giuseppe Ippolito ² , Rino Rappuoli ¹⁷



Affiliations

• PMID: 33667349
• PMCID: PMC7901298
• DOI: 10.1016/j.cell.2021.02.035

Free PMC article

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.