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Extremely potent human monoclonal antibodies from convalescent Covid-19 patients

View ORCID ProfileEmanuele Andreano, View ORCID ProfileEmanuele Nicastri, Ida Paciello, View ORCID ProfilePiero 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
doi: https://doi.org/10.1101/2020.10.07.328302
Emanuele Andreano
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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  • ORCID record for Emanuele Andreano
Emanuele Nicastri
4National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy
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Ida Paciello
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Piero Pileri
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Noemi Manganaro
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Giulia Piccini
2VisMederi S.r.l, Siena, Italy
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Alessandro Manenti
2VisMederi S.r.l, Siena, Italy
3VisMederi Research S.r.l., Siena, Italy
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Elisa Pantano
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Anna Kabanova
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
11Tumour Immunology Unit, Fondazione Toscana Life Sciences, Siena, Italy
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Marco Troisi
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
9Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
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Fabiola Vacca
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
9Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
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Dario Cardamone
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
10University of Turin, Turin, Italy
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Concetta De Santi
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Linda Benincasa
3VisMederi Research S.r.l., Siena, Italy
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Chiara Agrati
4National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy
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Maria Rosaria Capobianchi
4National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy
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Concetta Castilletti
4National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy
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Arianna Emiliozzi
5Department of Medical Biotechnologies, University of Siena, Siena, Italy
6Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy
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Massimiliano Fabbiani
6Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy
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Francesca Montagnani
5Department of Medical Biotechnologies, University of Siena, Siena, Italy
6Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy
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Lorenzo Depau
12MedBiotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena
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Jlenia Brunetti
12MedBiotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena
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Luisa Bracci
12MedBiotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena
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Emanuele Montomoli
2VisMederi S.r.l, Siena, Italy
3VisMederi Research S.r.l., Siena, Italy
7Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy
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Claudia Sala
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Giuseppe Ippolito
4National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy
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  • For correspondence: r.rappuoli@imperial.ac.uk
Rino Rappuoli
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
8Faculty of Medicine, Imperial College, London, United Kingdom
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  • For correspondence: r.rappuoli@imperial.ac.uk
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SUMMARY

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 Summary Extremely potent neutralizing human monoclonal antibodies isolated from Covid-19 convalescent patients for prophylactic and therapeutic interventions.

Competing Interest Statement

Rino Rappuoli is an employee of GSK group of companies. Emanuele Andreano, Anna Kabanova, Dario Cardamone, Concetta De Santi, Ida Paciello, Noemi Manganaro, Elisa Pantano, Piero Pileri, Claudia Sala, Marco Troisi, Fabiola Vacca and Rino Rappuoli are listed as inventors of full-length human monoclonal antibodies described in Italian patent applications n. 102020000015754 filed on June 30th 2020 and 102020000018955 filed on August 3rd 2020.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 07, 2020.
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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
bioRxiv 2020.10.07.328302; doi: https://doi.org/10.1101/2020.10.07.328302
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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
bioRxiv 2020.10.07.328302; doi: https://doi.org/10.1101/2020.10.07.328302

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