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

AbstractEffective 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.

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

作者: Wilson, I A ; Rathnasinghe, R ; McDanal, C ; Kahlaoui, N ; Coughlan, L ; Caniels, T G ; Liu, H ; Lemaître, J ; Ronk, A J ; Brinkkemper, M ; Gagnon, L ; Mire, C E ; Burger, J A ; Kuzmina, N A ; García-Sastre, A ; Contreras, V ; Bijl, Tpl ; Montefiori, D C ; Relouzat, F ; van Breemen, M J ; Naninck, T ; Marc, A ; Chesnais, V ; Diry, S ; Freyn, A W ; Poniman, M ; Maisonnasse, P ; Ho Tsong Fang, R ; van Schooten, J ; Le Grand, R ; Yuan, M ; Bukreyev, A ; Guedj, J ; St-Amant, N ; van der Werf, S ; Gonçalves, A ; van Gils, M J ; Chapon, C ; de Bree, G J ; Brouwer, Pjm ; Marlin, R ; Ginoux, E ; Sanders, R W ; Schotsaert, M ; Snitselaar, J L ; Osei-Twum, M ; Iershov, A ; Jangra, S ; Dereuddre-Bosquet, N ; Aldon, Y

AbstractOne year into the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), effective treatments are still needed1–3. Monoclonal antibodies, given alone or as part of a therapeutic cocktail, have shown promising results in patients, raising the hope that they could play an important role in preventing clinical deterioration in severely ill or in exposed, high risk individuals4–6. Here, we evaluated the prophylactic and therapeutic effect of COVA1-18 in vivo, a neutralizing antibody isolated from a convalescent patient7 and highly potent against the B.1.1.7. isolate8,9. In both prophylactic and therapeutic settings, SARS-CoV-2 remained undetectable in the lungs of COVA1-18 treated hACE2 mice. Therapeutic treatment also caused a dramatic 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 had a very strong antiviral activity in the upper respiratory compartments with an estimated reduction in viral infectivity of more than 95%, and prevented lymphopenia and extensive lung lesions. Modelling and experimental findings demonstrate that COVA1-18 has a strong antiviral activity in three different preclinical models and could be a valuable candidate for further clinical evaluation.

100 项与 COVA1-18 相关的药物交易

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