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iScience
. 2022 Jul 3;104705.
doi: 10.1016/j.isci.2022.104705. Online ahead of print.
Potent neutralizing anti-SARS-CoV-2 human antibodies cure infection with SARS-CoV-2 variants in hamster model
Maya Imbrechts 1 2 3 , Wim Maes 1 3 4 , Louanne Ampofo 1 3 , Nathalie Van den Berghe 2 , Bas Calcoen 4 , Dominique Van Looveren 5 , Winnie Kerstens 5 , Madina Rasulova 5 , Thomas Vercruysse 5 , Sam Noppen 6 , Rana Abdelnabi 6 7 , Caroline Foo 6 7 , Kevin Hollevoet 1 2 , Piet Maes 6 7 , Xin Zhang 6 7 , Dirk Jochmans 6 7 , Karen Ven 3 8 , Jeroen Lammertyn 3 8 , Karen Vanhoorelbeke 1 3 4 , Nico Callewaert 9 , Paul De Munter 10 11 , Dominique Schols 6 , Hendrik Jan Thibaut 5 , Johan Neyts 6 12 7 , Paul Declerck 1 2 3 , Nick Geukens 1 3
Affiliations
- PMID: 35813873
- PMCID: PMC9250818
- DOI: 10.1016/j.isci.2022.104705
Abstract
Treatment with neutralizing monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to COVID-19 management. Unfortunately, SARS-CoV-2 variants escape several of these recently approved mAbs, highlighting the need for additional discovery and development. In a convalescent COVID-19 patient, we identified six mAbs, classified in four epitope groups, that potently neutralized SARS-CoV-2 D614G, beta, gamma and delta infection in vitro, with three mAbs neutralizing omicron as well. In hamsters, mAbs 3E6 and 3B8 potently cured infection with SARS-CoV-2 Wuhan, beta and delta when administered post-viral infection at 5 mg/kg. Even at 0.2 mg/kg, 3B8 still reduced viral titers. Intramuscular delivery of DNA-encoded 3B8 resulted in in vivo mAb production of median serum levels up to 90 μg/ml, and protected hamsters against delta infection. Overall, our data mark 3B8 as a promising candidate against COVID-19, and highlight advances in both the identification and gene-based delivery of potent human mAbs.