COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models
Pauline Maisonnasse, Yoann Aldon, Aurélien Marc, Romain Marlin, Nathalie Dereuddre‐Bosquet, Natalia A. Kuzmina, Alec W. Freyn, Jonne L. Snitselaar, António Gonçalves, Tom G. Caniels, Judith A. Burger, Meliawati Poniman, Ilja Bontjer, Virginie Chesnais, Ségolène Diry, Anton Iershov, Adam J. Ronk, Sonia Jangra, Raveen Rathnasinghe, Philip J. M. Brouwer, Tom P. L. Bijl, Jelle van Schooten, Mitch Brinkkemper, Hejun Liu, Meng Yuan, Chad E. Mire, Mariëlle J. van Breemen, Vanessa Contreras, Thibaut Naninck, Julien Lemaître, Nidhal Kahlaoui, Francis Relouzat, Catherine Chapon, Raphaël Ho Tsong Fang, Charlene McDanal, Mary Osei-Twum, Natalie St-Amant, Luc Gagnon, David C. Montefiori, Ian A. Wilson, Eric Ginoux, Godelieve J. de Bree, Adolfo García‐Sastre, Michael Schotsaert, Lynda Coughlan, Alexander Bukreyev, Sylvie van der Werf, Jérémie Guedj, Rogier W. Sanders, Marit J. van Gils, Roger Le Grand
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.