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Extremely potent human monoclonal antibodies from convalescent Covid-19 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; Linda Benincasa; Chiara Agrati; Maria Rosaria Capobianchi; Concetta Castilletti; Arianna Emiliozzi; Massimiliano Fabbiani; Francesca Montagnani; Lorenzo Depau; Jlenia Brunetti; Luisa Bracci; Emanuele Montomoli; Claudia Sala; Giuseppe Ippolito; Rino Rappuoli.
Affiliation
  • Emanuele Andreano; Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
  • Emanuele Nicastri; National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy
  • Ida Paciello; Monoclonal Antibody Discovery (MAD) Lab - Fondazione Toscana Life Sciences
  • Piero Pileri; Monoclonal Antibody Discovery (MAD) Lab - Fondazione Toscana Life Sciences
  • Noemi Manganaro; Monoclonal Antibody Discovery (MAD) Lab - Fondazione Toscana Life Sciences
  • Giulia Piccini; VisMederi S.r.l, Siena, Italy
  • Alessandro Manenti; VisMederi S.r.l, Siena, Italy; VisMederi Research S.r.l., Siena, Italy
  • Elisa Pantano; Monoclonal Antibody Discovery (MAD) Lab - Fondazione Toscana Life Sciences
  • Anna Kabanova; Monoclonal Antibody Discovery (MAD) Lab - Fondazione Toscana Life Sciences; Tumour Immunology Unit, Fondazione Toscana Life Sciences, Siena, Italy
  • Marco Troisi; Monoclonal Antibody Discovery (MAD) Lab - Fondazione Toscana Life Sciences; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Ita
  • Fabiola Vacca; Monoclonal Antibody Discovery (MAD) Lab - Fondazione Toscana Life Sciences; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Ita
  • Dario Cardamone; Monoclonal Antibody Discovery (MAD) Lab - Fondazione Toscana Life Sciences; University of Turin, Turin, Italy
  • Concetta De Santi; Monoclonal Antibody Discovery (MAD) Lab - Fondazione Toscana Life Sciences
  • Linda Benincasa; VisMederi Research S.r.l., Siena, Italy
  • Chiara Agrati; National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy
  • Maria Rosaria Capobianchi; National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy
  • Concetta Castilletti; National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy
  • Arianna Emiliozzi; Department of Medical Biotechnologies, University of Siena, Siena, Italy; Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hosp
  • Massimiliano Fabbiani; Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy
  • Francesca Montagnani; Department of Medical Biotechnologies, University of Siena, Siena, Italy; Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hosp
  • Lorenzo Depau; MedBiotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena
  • Jlenia Brunetti; MedBiotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena
  • Luisa Bracci; 12MedBiotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena
  • Emanuele Montomoli; VisMederi S.r.l, Siena, Italy; VisMederi Research S.r.l., Siena, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy
  • Claudia Sala; Monoclonal Antibody Discovery (MAD) Lab - Fondazione Toscana Life Sciences
  • Giuseppe Ippolito; National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy
  • Rino Rappuoli; Monoclonal Antibody Discovery (MAD) Lab - Fondazione Toscana Life Sciences; Faculty of Medicine, Imperial College, London, United Kingdom
Preprint in English | bioRxiv | ID: ppbiorxiv-328302
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 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 SummaryExtremely potent neutralizing human monoclonal antibodies isolated from Covid-19 convalescent patients for prophylactic and therapeutic interventions.
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2020 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2020 Document type: Preprint
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