1. COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.
- Author
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Maisonnasse P, Aldon Y, Marc A, Marlin R, Dereuddre-Bosquet N, Kuzmina NA, Freyn AW, Snitselaar JL, Gonçalves A, Caniels TG, Burger JA, Poniman M, Bontjer I, Chesnais V, Diry S, Iershov A, Ronk AJ, Jangra S, Rathnasinghe R, Brouwer PJM, Bijl TPL, van Schooten J, Brinkkemper M, Liu H, Yuan M, Mire CE, van Breemen MJ, Contreras V, Naninck T, Lemaître J, Kahlaoui N, Relouzat F, Chapon C, Ho Tsong Fang R, McDanal C, Osei-Twum M, St-Amant N, Gagnon L, Montefiori DC, Wilson IA, Ginoux E, de Bree GJ, García-Sastre A, Schotsaert M, Coughlan L, Bukreyev A, van der Werf S, Guedj J, Sanders RW, van Gils MJ, and Le Grand R
- Subjects
- Angiotensin-Converting Enzyme 2 genetics, Animals, Antibodies, Monoclonal pharmacokinetics, Antiviral Agents pharmacokinetics, COVID-19 blood, COVID-19 immunology, COVID-19 virology, Disease Models, Animal, Drug Evaluation, Preclinical, Female, Humans, Lung metabolism, Lung virology, Macaca fascicularis, Male, Mesocricetus, Mice, Mice, Transgenic, SARS-CoV-2 isolation & purification, Tissue Distribution, Viral Load, Antibodies, Monoclonal administration & dosage, Antibodies, Neutralizing administration & dosage, Antiviral Agents administration & dosage, SARS-CoV-2 immunology, COVID-19 Drug Treatment
- 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., (© 2021. The Author(s).)
- Published
- 2021
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