COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models

Pauline Maisonnasse, Yoann Aldon, Aurélien Marc, Romain Marlin, Nathalie Dereuddre-Bosquet, Natalia A. Kuzmina, Alec W. Freyn, Jonne L. Snitselaar, Antonio Gonçalves, Tom G. Caniels, Judith A. Burger, Meliawati Poniman, Ilja Bontjer, Virginie Chesnais, Ségolène Diry, Anton Iershov, Adam J. Ronk, Sonia Jangra, Raveen Rathnasinghe, Philip J. M. Brouwer, Tom P. L. Bijl, Jelle Schooten, Mitch Brinkkemper, Hejun Liu, Meng Yuan, Chad E. Mire, Mariëlle J. Breemen, Vanessa Contreras, Thibaut Naninck, Julien Lemaître, Nidhal Kahlaoui, Francis Relouzat, Catherine Chapon, Raphaël Ho Tsong Fang, Charlene McDanal, Mary Osei-Twum, Natalie St-Amant, Luc Gagnon, David C. Montefiori, Ian A. Wilson, Eric Ginoux, Godelieve J. Bree, Adolfo García-Sastre, Michael Schotsaert, Lynda Coughlan, Alexander Bukreyev, Sylvie Werf, Jérémie Guedj, Rogier W. Sanders (), Marit J. Gils () and Roger Le Grand ()
Additional contact information
Pauline Maisonnasse: Fontenay-aux-Roses & Le Kremlin-Bicêtre
Yoann Aldon: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Aurélien Marc: Université de Paris, INSERM, IAME
Romain Marlin: Fontenay-aux-Roses & Le Kremlin-Bicêtre
Nathalie Dereuddre-Bosquet: Fontenay-aux-Roses & Le Kremlin-Bicêtre
Natalia A. Kuzmina: University of Texas Medical Branch at Galveston
Alec W. Freyn: Department of Microbiology, Icahn School of Medicine at Mount Sinai
Jonne L. Snitselaar: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Antonio Gonçalves: Université de Paris, INSERM, IAME
Tom G. Caniels: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Judith A. Burger: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Meliawati Poniman: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Ilja Bontjer: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Virginie Chesnais: Life and Soft
Ségolène Diry: Life and Soft
Anton Iershov: Life and Soft
Adam J. Ronk: University of Texas Medical Branch at Galveston
Sonia Jangra: Department of Microbiology, Icahn School of Medicine at Mount Sinai
Raveen Rathnasinghe: Department of Microbiology, Icahn School of Medicine at Mount Sinai
Philip J. M. Brouwer: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Tom P. L. Bijl: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Jelle Schooten: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Mitch Brinkkemper: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Hejun Liu: Department of Integrative Structural and Computational Biology, The Scripps Research Institute
Meng Yuan: Department of Integrative Structural and Computational Biology, The Scripps Research Institute
Chad E. Mire: Galveston National Laboratory
Mariëlle J. Breemen: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Vanessa Contreras: Fontenay-aux-Roses & Le Kremlin-Bicêtre
Thibaut Naninck: Fontenay-aux-Roses & Le Kremlin-Bicêtre
Julien Lemaître: Fontenay-aux-Roses & Le Kremlin-Bicêtre
Nidhal Kahlaoui: Fontenay-aux-Roses & Le Kremlin-Bicêtre
Francis Relouzat: Fontenay-aux-Roses & Le Kremlin-Bicêtre
Catherine Chapon: Fontenay-aux-Roses & Le Kremlin-Bicêtre
Raphaël Ho Tsong Fang: Fontenay-aux-Roses & Le Kremlin-Bicêtre
Charlene McDanal: Duke Human Vaccine Institute & Department of Surgery
Mary Osei-Twum: Nexelis, Laval
Natalie St-Amant: Nexelis, Laval
Luc Gagnon: Nexelis, Laval
David C. Montefiori: Duke Human Vaccine Institute & Department of Surgery
Ian A. Wilson: Department of Integrative Structural and Computational Biology, The Scripps Research Institute
Eric Ginoux: Life and Soft
Godelieve J. Bree: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Adolfo García-Sastre: Department of Microbiology, Icahn School of Medicine at Mount Sinai
Michael Schotsaert: Department of Microbiology, Icahn School of Medicine at Mount Sinai
Lynda Coughlan: Department of Microbiology, Icahn School of Medicine at Mount Sinai
Alexander Bukreyev: University of Texas Medical Branch at Galveston
Sylvie Werf: Université de Paris
Jérémie Guedj: Université de Paris, INSERM, IAME
Rogier W. Sanders: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Marit J. Gils: University of Amsterdam, Amsterdam Institute for Infection and Immunity
Roger Le Grand: Fontenay-aux-Roses & Le Kremlin-Bicêtre

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract Effective treatments against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Monoclonal antibodies have shown promising results in patients. Here, we evaluate the in vivo prophylactic and therapeutic effect of COVA1-18, a neutralizing antibody highly potent against the B.1.1.7 isolate. In both prophylactic and therapeutic settings, SARS-CoV-2 remains undetectable in the lungs of treated hACE2 mice. Therapeutic treatment also causes a reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg-1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 shows very strong antiviral activity in the upper respiratory compartments. Using a mathematical model, we estimate that COVA1-18 reduces viral infectivity by more than 95% in these compartments, preventing lymphopenia and extensive lung lesions. Our findings demonstrate that COVA1-18 has a strong antiviral activity in three preclinical models and could be a valuable candidate for further clinical evaluation.

Date: 2021
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DOI: 10.1038/s41467-021-26354-0

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