Extremely potent human monoclonal antibodies from COVID-19 convalescent patients

Cell. 2021 Apr 1;184(7):1821-1835.e16. doi: 10.1016/j.cell.2021.02.035. | PubMed

Emanuele Andreano¹, Emanuele Nicastri², Ida Paciello¹, Piero Pileri¹, Noemi Manganaro¹, Giulia Piccini³, Alessandro Manenti⁴, Elisa Pantano¹, Anna Kabanova⁵, Marco Troisi⁶, Fabiola Vacca⁶, Dario Cardamone⁷, Concetta De Santi¹, Jonathan L Torres⁸, Gabriel Ozorowski⁸, Linda Benincasa⁹, Hyesun Jang¹⁰, Cecilia Di Genova¹¹, Lorenzo Depau¹², Jlenia Brunetti¹², Chiara Agrati², Maria Rosaria Capobianchi², Concetta Castilletti², Arianna Emiliozzi¹³, Massimiliano Fabbiani¹⁴, Francesca Montagnani¹³, Luisa Bracci¹², Giuseppe Sautto¹⁰, Ted M Ross¹⁵, Emanuele Montomoli¹⁶, Nigel Temperton¹¹, Andrew B Ward⁸, Claudia Sala¹, Giuseppe Ippolito², Rino Rappuoli¹⁷

1. Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy.
2. National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy.
3. VisMederi S.r.l, Siena, Italy.
4. VisMederi S.r.l, Siena, Italy; VisMederi Research S.r.l., Siena, Italy.
5. Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy; Tumour Immunology Unit, Fondazione Toscana Life Sciences, Siena, Italy.
6. Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
7. Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy; University of Turin, Turin, Italy.
8. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
9. VisMederi Research S.r.l., Siena, Italy.
10. Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA.
11. Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent, Chatham, UK.
12. MedBiotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
13. Department of Medical Biotechnologies, University of Siena, Siena, Italy; Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy.
14. Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy.
15. Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA; Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
16. VisMederi S.r.l, Siena, Italy; VisMederi Research S.r.l., Siena, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
17. Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy; Faculty of Medicine, Imperial College, London, UK. Electronic address: rino.r.rappuoli@gsk.com.

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.

Presented By Emanuele Andreano | ORCID iD