摘要：SummaryTreatment 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 infectionin 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 inin vivomAb 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.Graphical abstractDisplay OmittedHighlights•Discovery of potent neutralizing antibodies classified in different epitope groups•Antibodies neutralize SARS-CoV-2 D614G, beta, gamma, delta, and omicronin vitro•Selected antibodies potently treat SARS-CoV-2 infection in hamsters at low doses•Intramuscular delivery of DNA-encoded 3B8 protects hamsters against infectionImmunology; Virology.
