Journal Article

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

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

2021

Overview

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. Monoclonal antibodies show great promise in treating Covid-19 patients. Here, Maisonnasse, Aldon and colleagues report pre-clinical results for COVA1-18 and demonstrate that it reduces viral infectivity in three animal models with over 95% efficacy in macaques upper respiratory tract.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/88 / 38/91 / 631/250/251 / 631/250/255 / 631/326/596/4130 / 692/308/2778 / 82/1 / Angiotensin-Converting Enzyme 2 - genetics / Animal models / Animals / Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal - pharmacokinetics / Antibodies, Neutralizing - administration & dosage / Antiviral activity / Antiviral Agents - administration & dosage / Antiviral Agents - pharmacokinetics / Antiviral drugs / Compartments / Coronaviruses / COVID-19 / COVID-19 - blood / COVID-19 - immunology / COVID-19 - virology / COVID-19 Drug Treatment / Disease Models, Animal / Drug Evaluation, Preclinical / Female / Hamsters / Humanities and Social Sciences / Humans / Infectivity / Life Sciences / Lung - metabolism / Lung - virology / Lungs / Lymphopenia / Macaca fascicularis / Male / Mathematical models / Mesocricetus / Mice / Mice, Transgenic / Monoclonal antibodies / multidisciplinary / Neutralizing / Patients / Respiratory diseases / Respiratory tract / SARS-CoV-2 - immunology / SARS-CoV-2 - isolation & purification / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Tissue Distribution / Viral diseases / Viral Load