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

COVA1-18 中和抗体在三种临床前模型中可预防 SARS-CoV-2

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作者:P Maisonnasse, Y Aldon, A Marc, R Marlin, N Dereuddre-Bosquet, N A Kuzmina, A W Freyn, J L Snitselaar, A Gonçalves, T G Caniels, J A Burger, M Poniman, V Chesnais, S Diry, A Iershov, A J Ronk, S Jangra, R Rathnasinghe, Pjm Brouwer, Tpl Bijl, J van Schooten, M Brinkkemper, H Liu, M Yuan, C E Mire, M

Abstract

One year into the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), effective treatments are still needed 1-3 . 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 individuals 4-6 . Here, we evaluated the prophylactic and therapeutic effect of COVA1-18 in vivo , a neutralizing antibody isolated from a convalescent patient 7 and highly potent against the B.1.1.7. isolate 8,9 . 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.

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