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

Authors :
Maisonnasse, Pauline
Aldon, Yoann
Marc, Aurélien
Marlin, Romain
Dereuddre-Bosquet, Nathalie
Kuzmina, Natalia A.
Freyn, Alec W.
Snitselaar, Jonne L.
Gonçalves, Antonio
Caniels, Tom G.
Burger, Judith A.
Poniman, Meliawati
Bontjer, Ilja
Chesnais, Virginie
Diry, Ségolène
Iershov, Anton
Ronk, Adam J.
Jangra, Sonia
Rathnasinghe, Raveen
Brouwer, Philip J. M.
Bijl, Tom P. L.
van Schooten, Jelle
Brinkkemper, Mitch
Liu, Hejun
Yuan, Meng
Mire, Chad E.
van Breemen, Mariëlle J.
Contreras, Vanessa
Naninck, Thibaut
Lemaître, Julien
Kahlaoui, Nidhal
Relouzat, Francis
Chapon, Catherine
Ho Tsong Fang, Raphaël
McDanal, Charlene
Osei-Twum, Mary
St-Amant, Natalie
Gagnon, Luc
Montefiori, David C.
Wilson, Ian A.
Ginoux, Eric
de Bree, Godelieve J.
García-Sastre, Adolfo
Schotsaert, Michael
Coughlan, Lynda
Bukreyev, Alexander
van der Werf, Sylvie
Guedj, Jérémie
Sanders, Rogier W.
van Gils, Marit J.
Le Grand, Roger
Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB)
Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay
Imperial College London
Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137))
Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord
University of Texas Medical Branch at Galveston
Icahn School of Medicine at Mount Sinai [New York] (MSSM)
Department of Medical Microbiology and Infection Prevention [Amsterdam]
University of Amsterdam [Amsterdam] (UvA)
Amsterdam UMC - Amsterdam University Medical Center
Life and Soft
The Scripps Research Institute [La Jolla, San Diego]
Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2))
Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé)
Institut des Agents Infectieux [Lyon] (IAI)
Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)
This study was supported by the Netherlands Organization for Scientific Research (NWO) Vici grant (to R.W.S.), the Bill & Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grant INV-002022 (to R.W.S.), the Fondation Dormeur, Vaduz (to R.W.S. and to M.J.v.G.) and Health Holland PPS-allowance LSHM20040 (to M.J.v.G.). M.J.v.G. is a recipient of an AMC Fellowship, Amsterdam UMC and a COVID-19 grant of the Amsterdam Institute of Infection and Immunity, the Netherlands. R.W.S and M.J.v.G. are recipients of support from the University of Amsterdam Proof of Concept fund (contract no 200421) as managed by Innovation Exchange Amsterdam (IXA). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the 'Programme Investissements d’Avenir', managed by the ANR under reference ANR-11-INBS-0008. The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT’s facilities and imaging technologies. The NHP study received financial support from REACTing, the Fondation pour la Recherche Médicale (FRM, France
AM-CoV-Path) and the European Infrastructure TRANSVAC2 (730964). The virus stock used in NHPs was obtained through the EVAg platform (https://www.european-virus-archive.com/), funded by H2020 (653316). Work performed at Duke University was supported by the CoVPN grant (NIH AI46705) (to D.C.M.). The Ad5-hACE2 mouse work was supported in part by NIAID R21AI157606 (L.C.), and was partially supported by CRIP (Center for Research for Influenza Pathogenesis), an NIAID supported Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C) (A.G.S.), by supplements to NIAID grant U19AI135972 and DoD grant W81XWH-20-1-0270, by the Defense Advanced Research Projects Agency (HR0011-19-2-0020), and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384) and anonymous donors to A.G.S. Part of this study was supported by the Bill and Melinda Gates Foundation through grants OPP1170236 and INV-004923 (I.A.W.) and through the Global Health Vaccine Accelerator Platforms (GH-VAP) and the Coronavirus Immunotherapy Consortium (CoVIC) (Nexelis).
ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011)
ANR-20-COVI-0021,AM-Cov-Path,Pathogénèse de l'infection SARS-Cov-2 dans un modèle de primates non humains : un modèle pour les traitements et la prévention(2020)
European Project: 730964, H2020, RIA,H2020-INFRAIA-2016-1,TRANSVAC2(2017)
European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015)
Medical Microbiology and Infection Prevention
Graduate School
AII - Infectious diseases
Infectious diseases
APH - Aging & Later Life
APH - Global Health
Source :
Nature Communications, Nature Communications, 2021, 12 (1), pp.6097. ⟨10.1038/s41467-021-26354-0⟩, Nature Communications, Vol 12, Iss 1, Pp 1-10 (2021), Nature communications, 12(1):6097. Nature Publishing Group, Research Square, article-version (status) pre, article-version (number) 1
Publication Year :
2021
Publisher :
HAL CCSD, 2021.

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.<br />Monoclonal antibodies show great promise in treating Covid-19 patients. Here, Maisonnasse, Aldon and colleagues report pre-clinical results for COVA1-18 and demonstrate that it reduces viral infectivity in three animal models with over 95% efficacy in macaques upper respiratory tract.

Details

Language :
English
ISSN :
20411723
Database :
OpenAIRE
Journal :
Nature Communications, Nature Communications, 2021, 12 (1), pp.6097. ⟨10.1038/s41467-021-26354-0⟩, Nature Communications, Vol 12, Iss 1, Pp 1-10 (2021), Nature communications, 12(1):6097. Nature Publishing Group, Research Square, article-version (status) pre, article-version (number) 1
Accession number :
edsair.doi.dedup.....4ac96f13a4254c46ea6971155f1d168f
Full Text :
https://doi.org/10.1038/s41467-021-26354-0⟩