tetano
Editor, Senior Moderator
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[SUP] 1 2 3 [/SUP], Wim Maes[SUP] 1 3 4 [/SUP], Louanne Ampofo[SUP] 1 3 [/SUP], Nathalie Van den Berghe[SUP] 2 [/SUP], Bas Calcoen[SUP] 4 [/SUP], Dominique Van Looveren[SUP] 5 [/SUP], Winnie Kerstens[SUP] 5 [/SUP], Madina Rasulova[SUP] 5 [/SUP], Thomas Vercruysse[SUP] 5 [/SUP], Sam Noppen[SUP] 6 [/SUP], Rana Abdelnabi[SUP] 6 7 [/SUP], Caroline Foo[SUP] 6 7 [/SUP], Kevin Hollevoet[SUP] 1 2 [/SUP], Piet Maes[SUP] 6 7 [/SUP], Xin Zhang[SUP] 6 7 [/SUP], Dirk Jochmans[SUP] 6 7 [/SUP], Karen Ven[SUP] 3 8 [/SUP], Jeroen Lammertyn[SUP] 3 8 [/SUP], Karen Vanhoorelbeke[SUP] 1 3 4 [/SUP], Nico Callewaert[SUP] 9 [/SUP], Paul De Munter[SUP] 10 11 [/SUP], Dominique Schols[SUP] 6 [/SUP], Hendrik Jan Thibaut[SUP] 5 [/SUP], Johan Neyts[SUP] 6 12 7 [/SUP], Paul Declerck[SUP] 1 2 3 [/SUP], Nick Geukens[SUP] 1 3 [/SUP]
Affiliations
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.
. 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[SUP] 1 2 3 [/SUP], Wim Maes[SUP] 1 3 4 [/SUP], Louanne Ampofo[SUP] 1 3 [/SUP], Nathalie Van den Berghe[SUP] 2 [/SUP], Bas Calcoen[SUP] 4 [/SUP], Dominique Van Looveren[SUP] 5 [/SUP], Winnie Kerstens[SUP] 5 [/SUP], Madina Rasulova[SUP] 5 [/SUP], Thomas Vercruysse[SUP] 5 [/SUP], Sam Noppen[SUP] 6 [/SUP], Rana Abdelnabi[SUP] 6 7 [/SUP], Caroline Foo[SUP] 6 7 [/SUP], Kevin Hollevoet[SUP] 1 2 [/SUP], Piet Maes[SUP] 6 7 [/SUP], Xin Zhang[SUP] 6 7 [/SUP], Dirk Jochmans[SUP] 6 7 [/SUP], Karen Ven[SUP] 3 8 [/SUP], Jeroen Lammertyn[SUP] 3 8 [/SUP], Karen Vanhoorelbeke[SUP] 1 3 4 [/SUP], Nico Callewaert[SUP] 9 [/SUP], Paul De Munter[SUP] 10 11 [/SUP], Dominique Schols[SUP] 6 [/SUP], Hendrik Jan Thibaut[SUP] 5 [/SUP], Johan Neyts[SUP] 6 12 7 [/SUP], Paul Declerck[SUP] 1 2 3 [/SUP], Nick Geukens[SUP] 1 3 [/SUP]
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.