ArticleOA
Author: Jangra, Sonia ; Iershov, Anton ; Snitselaar, Jonne L ; Caniels, Tom G ; Guedj, Jérémie ; Gonçalves, Antonio ; Contreras, Vanessa ; van Schooten, Jelle ; Wilson, Ian A ; McDanal, Charlene ; Poniman, Meliawati ; Maisonnasse, Pauline ; van Breemen, Mariëlle J ; Kahlaoui, Nidhal ; Schotsaert, Michael ; Relouzat, Francis ; Coughlan, Lynda ; Ho Tsong Fang, Raphaël ; Sanders, Rogier W ; Kuzmina, Natalia A ; Chapon, Catherine ; Osei-Twum, Mary ; Mire, Chad E ; Freyn, Alec W ; García-Sastre, Adolfo ; Liu, Hejun ; Bijl, Tom P L ; Montefiori, David C ; Burger, Judith A ; Brinkkemper, Mitch ; Brouwer, Philip J M ; de Bree, Godelieve J ; Diry, Ségolène ; Aldon, Yoann ; Bontjer, Ilja ; van der Werf, Sylvie ; Le Grand, Roger ; Marlin, Romain ; Naninck, Thibaut ; Ronk, Adam J ; St-Amant, Natalie ; Ginoux, Eric ; van Gils, Marit J ; Lemaître, Julien ; Dereuddre-Bosquet, Nathalie ; Rathnasinghe, Raveen ; Gagnon, Luc ; Chesnais, Virginie ; Marc, Aurélien ; Yuan, Meng ; Bukreyev, Alexander
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.