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

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

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.