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

Author

Listed:
  • 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
    Galveston National Laboratory)

  • 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
    Galveston National Laboratory)

  • Sonia Jangra

    (Department of Microbiology, Icahn School of Medicine at Mount Sinai)

  • Raveen Rathnasinghe

    (Department of Microbiology, Icahn School of Medicine at Mount Sinai
    Graduate School of Biomedical Sciences, 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
    University of Texas Medical Branch at Galveston)

  • 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
    Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai
    The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
    Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai)

  • Michael Schotsaert

    (Department of Microbiology, Icahn School of Medicine at Mount Sinai
    Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai)

  • Lynda Coughlan

    (Department of Microbiology, Icahn School of Medicine at Mount Sinai
    University of Maryland School of Medicine, Department of Microbiology and Immunology and Center for Vaccine Development and Global Health (CVD))

  • Alexander Bukreyev

    (University of Texas Medical Branch at Galveston
    Galveston National Laboratory
    University of Texas Medical Branch at Galveston)

  • Sylvie Werf

    (Université de Paris
    National Reference Center for Respiratory Viruses, Institut Pasteur)

  • Jérémie Guedj

    (Université de Paris, INSERM, IAME)

  • Rogier W. Sanders

    (University of Amsterdam, Amsterdam Institute for Infection and Immunity
    Weill Medical College of Cornell University)

  • Marit J. Gils

    (University of Amsterdam, Amsterdam Institute for Infection and Immunity)

  • Roger Le Grand

    (Fontenay-aux-Roses & Le Kremlin-Bicêtre)

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.

Suggested Citation

  • 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 , 2021. "COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26354-0
    DOI: 10.1038/s41467-021-26354-0
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    References listed on IDEAS

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    Cited by:

    1. Mathieu Claireaux & Tom G. Caniels & Marlon Gast & Julianna Han & Denise Guerra & Gius Kerster & Barbera D. C. Schaik & Aldo Jongejan & Angela I. Schriek & Marloes Grobben & Philip J. M. Brouwer & Kar, 2022. "A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Romain Marlin & Delphine Desjardins & Vanessa Contreras & Guillaume Lingas & Caroline Solas & Pierre Roques & Thibaut Naninck & Quentin Pascal & Sylvie Behillil & Pauline Maisonnasse & Julien Lemaitre, 2022. "Antiviral efficacy of favipiravir against Zika and SARS-CoV-2 viruses in non-human primates," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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