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

Pauline Maisonnasse(Inserm), Yoann Aldon(Amsterdam University Medical Centers), Aurélien Marc(Inserm), Romain Marlin(Inserm), Nathalie Dereuddre‐Bosquet(Inserm), Natalia A. Kuzmina(Galveston College), Alec W. Freyn(Icahn School of Medicine at Mount Sinai), Jonne L. Snitselaar(Amsterdam University Medical Centers), António Gonçalves(Inserm), Tom G. Caniels(Amsterdam University Medical Centers), Judith A. Burger(Amsterdam University Medical Centers), Meliawati Poniman(Amsterdam University Medical Centers), Ilja Bontjer(Amsterdam University Medical Centers), Virginie Chesnais(AR2i), Ségolène Diry(AR2i), Anton Iershov(AR2i), Adam J. Ronk(Galveston College), Sonia Jangra(Icahn School of Medicine at Mount Sinai), Raveen Rathnasinghe(Icahn School of Medicine at Mount Sinai), Philip J. M. Brouwer(Amsterdam University Medical Centers), Tom P. L. Bijl(Amsterdam University Medical Centers), Jelle van Schooten(Amsterdam University Medical Centers), Mitch Brinkkemper(Amsterdam University Medical Centers), Hejun Liu(Scripps Research Institute), Meng Yuan(Scripps Research Institute), Chad E. Mire(Galveston College), Mariëlle J. van Breemen(Amsterdam University Medical Centers), Vanessa Contreras(Inserm), Thibaut Naninck(Inserm), Julien Lemaître(Inserm), Nidhal Kahlaoui(Inserm), Francis Relouzat(Inserm), Catherine Chapon(Inserm), Raphaël Ho Tsong Fang(Inserm), Charlene McDanal, Mary Osei-Twum, Natalie St-Amant, Luc Gagnon, David C. Montefiori, Ian A. Wilson(Scripps Research Institute), Eric Ginoux(AR2i), Godelieve J. de Bree(Amsterdam University Medical Centers), Adolfo García‐Sastre(Icahn School of Medicine at Mount Sinai), Michael Schotsaert(Icahn School of Medicine at Mount Sinai), Lynda Coughlan(University of Maryland, Baltimore), Alexander Bukreyev(Galveston College), Sylvie van der Werf(Centre National de la Recherche Scientifique), Jérémie Guedj(Inserm), Rogier W. Sanders(Cornell University), Marit J. van Gils(Amsterdam University Medical Centers), Roger Le Grand(Inserm)
Nature Communications
October 20, 2021
Cited by 54Open Access
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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.


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