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

Pauline Maisonnasse (1) , Yoann Aldon (2) , Aurélien Marc (3) , Romain Marlin (1) , Nathalie Dereuddre-Bosquet (1) , Natalia Kuzmina (4) , Alec Freyn (5) , Jonne Snitselaar (6) , Antonio Gonçalves (3) , Tom Caniels (6) , Judith Burger (6) , Meliawati Poniman (6) , Ilja Bontjer (7) , Virginie Chesnais (8) , Ségolène Diry (8) , Anton Iershov (8) , Adam Ronk , Sonia Jangra (5) , Raveen Rathnasinghe (5) , Philip Brouwer (6) , Tom Bijl (6) , Jelle van Schooten , Mitch Brinkkemper , Hejun Liu (9) , Meng Yuan (9) , Chad Mire , Mariëlle van Breemen , Vanessa Contreras (1) , Thibaut Naninck (1) , Julien Lemaître (1) , Nidhal Kahlaoui (1) , Francis Relouzat (1) , Catherine Chapon , Raphaël Ho Tsong Fang , Charlene Mcdanal , Mary Osei-Twum , Natalie St-Amant , Luc Gagnon , David Montefiori , Ian Wilson , Eric Ginoux , Godelieve de Bree , Adolfo García-Sastre , Michael Schotsaert , Lynda Coughlan , Alexander Bukreyev (4) , Sylvie van der Werf (10, 11) , Jérémie Guedj (3) , Rogier Sanders (6) , Marit van Gils (6) , Roger Le Grand (1)

1 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
2 Imperial College London
3 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
4 University of Texas Medical Branch at Galveston
5 MSSM - Icahn School of Medicine at Mount Sinai [New York]
6 Department of Medical Microbiology and Infection Prevention [Amsterdam]
7 Amsterdam UMC - Amsterdam University Medical Center
8 Life and Soft
9 The Scripps Research Institute [La Jolla, San Diego]
10 GMV-ARN (UMR_3569 / U-Pasteur_2) - Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses
11 CNR - laboratoire associé - Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon]

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.

Domains: Life Sciences [q-bio]

Pauline Maisonnasse, Yoann Aldon, Aurélien Marc, Romain Marlin, Nathalie Dereuddre-Bosquet, et al.. COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models. Nature Communications, 2021, 12 (1), pp.6097. ⟨10.1038/s41467-021-26354-0⟩. ⟨pasteur-04098221⟩