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COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.
Maisonnasse, P; Aldon, Y; Marc, A; Marlin, R; Dereuddre-Bosquet, N; Kuzmina, N A; Freyn, A W; Snitselaar, J L; Gonçalves, A; Caniels, T G; Burger, J A; Poniman, M; Chesnais, V; Diry, S; Iershov, A; Ronk, A J; Jangra, S; Rathnasinghe, R; Brouwer, Pjm; Bijl, Tpl; van Schooten, J; Brinkkemper, M; Liu, H; Yuan, M; Mire, C E; van Breemen, M J; Contreras, V; Naninck, T; Lemaître, J; Kahlaoui, N; Relouzat, F; Chapon, C; Ho Tsong Fang, R; McDanal, C; Osei-Twum, M; St-Amant, N; Gagnon, L; Montefiori, D C; Wilson, I A; Ginoux, E; de Bree, G J; García-Sastre, A; Schotsaert, M; Coughlan, L; Bukreyev, A; van der Werf, S; Guedj, J; Sanders, R W; van Gils, M J; Le Grand, R.
Afiliação
  • Maisonnasse P; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
  • Aldon Y; Departments of Medical Microbiology of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105 AZ, Amsterdam, The Netherlands.
  • Marc A; Université de Paris, INSERM, IAME, F-75018 Paris, France.
  • Marlin R; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
  • Dereuddre-Bosquet N; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
  • Kuzmina NA; Department of Pathology, University of Texas Medical Branch at Galveston, Texas, USA.
  • Freyn AW; Galveston National Laboratory, Texas, USA.
  • Snitselaar JL; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York (NY), USA.
  • Gonçalves A; Departments of Medical Microbiology of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105 AZ, Amsterdam, The Netherlands.
  • Caniels TG; Université de Paris, INSERM, IAME, F-75018 Paris, France.
  • Burger JA; Departments of Medical Microbiology of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105 AZ, Amsterdam, The Netherlands.
  • Poniman M; Departments of Medical Microbiology of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105 AZ, Amsterdam, The Netherlands.
  • Chesnais V; Departments of Medical Microbiology of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105 AZ, Amsterdam, The Netherlands.
  • Diry S; Life and Soft, 92350 Le Plessis-Robinson, France.
  • Iershov A; Life and Soft, 92350 Le Plessis-Robinson, France.
  • Ronk AJ; Life and Soft, 92350 Le Plessis-Robinson, France.
  • Jangra S; Department of Pathology, University of Texas Medical Branch at Galveston, Texas, USA.
  • Rathnasinghe R; Galveston National Laboratory, Texas, USA.
  • Brouwer P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York (NY), USA.
  • Bijl T; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York (NY), USA.
  • van Schooten J; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York (NY), USA.
  • Brinkkemper M; Departments of Medical Microbiology of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105 AZ, Amsterdam, The Netherlands.
  • Liu H; Departments of Medical Microbiology of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105 AZ, Amsterdam, The Netherlands.
  • Yuan M; Departments of Medical Microbiology of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105 AZ, Amsterdam, The Netherlands.
  • Mire CE; Departments of Medical Microbiology of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105 AZ, Amsterdam, The Netherlands.
  • van Breemen MJ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Contreras V; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Naninck T; Galveston National Laboratory, Texas, USA.
  • Lemaître J; Department of Microbiology, University of Texas Medical Branch at Galveston, Texas, USA.
  • Kahlaoui N; Departments of Medical Microbiology of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105 AZ, Amsterdam, The Netherlands.
  • Relouzat F; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
  • Chapon C; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
  • Ho Tsong Fang R; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
  • McDanal C; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
  • Osei-Twum M; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
  • St-Amant N; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
  • Gagnon L; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
  • Montefiori DC; Duke Human Vaccine Institute & Department of Surgery, Durham, NC 27710, USA.
  • Wilson IA; Nexelis, Laval, Québec, Canada.
  • Ginoux E; Nexelis, Laval, Québec, Canada.
  • de Bree GJ; Nexelis, Laval, Québec, Canada.
  • García-Sastre A; Duke Human Vaccine Institute & Department of Surgery, Durham, NC 27710, USA.
  • Schotsaert M; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Coughlan L; Life and Soft, 92350 Le Plessis-Robinson, France.
  • Bukreyev A; Internal Medicine of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105 AZ, Amsterdam, The Netherlands.
  • van der Werf S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York (NY), USA.
  • Guedj J; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York (NY), USA.
  • Sanders RW; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York (NY), USA.
  • van Gils MJ; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York (NY), USA.
  • Le Grand R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York (NY), USA.
Res Sq ; 2021 Feb 15.
Article em En | MEDLINE | ID: mdl-33619476
ABSTRACT
One year into the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), effective treatments are still needed 1-3 . Monoclonal antibodies, given alone or as part of a therapeutic cocktail, have shown promising results in patients, raising the hope that they could play an important role in preventing clinical deterioration in severely ill or in exposed, high risk individuals 4-6 . Here, we evaluated the prophylactic and therapeutic effect of COVA1-18 in vivo , a neutralizing antibody isolated from a convalescent patient 7 and highly potent against the B.1.1.7. isolate 8,9 . In both prophylactic and therapeutic settings, SARS-CoV-2 remained undetectable in the lungs of COVA1-18 treated hACE2 mice. Therapeutic treatment also caused a dramatic 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 had a very strong antiviral activity in the upper respiratory compartments with an estimated reduction in viral infectivity of more than 95%, and prevented lymphopenia and extensive lung lesions. Modelling and experimental findings demonstrate that COVA1-18 has a strong antiviral activity in three different preclinical models and could be a valuable candidate for further clinical evaluation.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article