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

Author:

Maisonnasse PaulineORCID,Aldon YoannORCID,Marc Aurélien,Marlin RomainORCID,Dereuddre-Bosquet NathalieORCID,Kuzmina Natalia A.ORCID,Freyn Alec W.ORCID,Snitselaar Jonne L.,Gonçalves AntonioORCID,Caniels Tom G.ORCID,Burger Judith A.,Poniman Meliawati,Bontjer IljaORCID,Chesnais Virginie,Diry Ségolène,Iershov Anton,Ronk Adam J.ORCID,Jangra Sonia,Rathnasinghe Raveen,Brouwer Philip J. M.,Bijl Tom P. L.,van Schooten JelleORCID,Brinkkemper Mitch,Liu Hejun,Yuan MengORCID,Mire Chad E.ORCID,van Breemen Mariëlle J.,Contreras Vanessa,Naninck ThibautORCID,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.ORCID,Ginoux Eric,de Bree Godelieve J.,García-Sastre AdolfoORCID,Schotsaert MichaelORCID,Coughlan LyndaORCID,Bukreyev AlexanderORCID,van der Werf SylvieORCID,Guedj JérémieORCID,Sanders Rogier W.,van Gils Marit J.,Le Grand RogerORCID

Abstract

AbstractEffective 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.

Funder

Bill and Melinda Gates Foundation

Division of Intramural Research, National Institute of Allergy and Infectious Diseases

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Agence Nationale de la Recherche

Fondation Bettencourt Schueller

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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