iScience (Aug 2022)

Potent neutralizing anti-SARS-CoV-2 human antibodies cure infection with SARS-CoV-2 variants in hamster model

  • Maya Imbrechts,
  • Wim Maes,
  • Louanne Ampofo,
  • Nathalie Van den Berghe,
  • Bas Calcoen,
  • Dominique Van Looveren,
  • Winnie Kerstens,
  • Madina Rasulova,
  • Thomas Vercruysse,
  • Sam Noppen,
  • Rana Abdelnabi,
  • Caroline Foo,
  • Kevin Hollevoet,
  • Piet Maes,
  • Xin Zhang,
  • Dirk Jochmans,
  • Karen Ven,
  • Jeroen Lammertyn,
  • Karen Vanhoorelbeke,
  • Nico Callewaert,
  • Paul De Munter,
  • Dominique Schols,
  • Hendrik Jan Thibaut,
  • Johan Neyts,
  • Paul Declerck,
  • Nick Geukens

Journal volume & issue
Vol. 25, no. 8
p. 104705

Abstract

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Summary: 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 patient with COVID-19, 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.

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