TY - JOUR T1 - The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2 JF - bioRxiv DO - 10.1101/2021.03.09.434607 SP - 2021.03.09.434607 AU - Andrea L. Cathcart AU - Colin Havenar-Daughton AU - Florian A. Lempp AU - Daphne Ma AU - Michael A. Schmid AU - Maria L. Agostini AU - Barbara Guarino AU - Julia Di iulio AU - Laura E. Rosen AU - Heather Tucker AU - Joshua Dillen AU - Sambhavi Subramanian AU - Barbara Sloan AU - Siro Bianchi AU - Dora Pinto AU - Christian Saliba AU - Jason A Wojcechowskyj AU - Julia Noack AU - Jiayi Zhou AU - Hannah Kaiser AU - Arthur Chase AU - Martin Montiel-Ruiz AU - Exequiel Dellota, Jr. AU - Arnold Park AU - Roberto Spreafico AU - Anna Sahakyan AU - Elvin J. Lauron AU - Nadine Czudnochowski AU - Elisabetta Cameroni AU - Sarah Ledoux AU - Adam Werts AU - Christophe Colas AU - Leah Soriaga AU - Amalio Telenti AU - Lisa A. Purcell AU - Seungmin Hwang AU - Gyorgy Snell AU - Herbert W. Virgin AU - Davide Corti AU - Christy M. Hebner Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/07/26/2021.03.09.434607.abstract N2 - VIR-7831 and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). VIR-7831 and VIR-7832 were derived from a parent antibody (S309) isolated from memory B cells of a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) survivor. Both mAbs contain an “LS” mutation in the Fc region to prolong serum half-life and potentially enhance distribution to the respiratory mucosa. In addition, VIR-7832 encodes an Fc GAALIE mutation that has been shown previously to evoke CD8+ T-cells in the context of an in vivo viral respiratory infection. VIR-7831 and VIR-7832 potently neutralize wild-type and variant authentic virus in vitro as well as variant pseudotyped viruses. In addition, they retain activity against monoclonal antibody resistance mutations conferring reduced susceptibility to currently authorized mAbs. The VIR-7831/VIR-7832 epitope does not overlap with mutational sites in current variants of concern and continues to be highly conserved among circulating sequences consistent with the high barrier to resistance observed in vitro. Furthermore, both mAbs can recruit effector mechanisms in vitro that may contribute to clinical efficacy via elimination of infected host cells. In vitro studies with these mAbs demonstrated no enhancement of infection. In a Syrian Golden hamster proof-of concept wildtype SARS-CoV-2 infection model, animals treated with VIR-7831 had less weight loss, and significantly decreased total viral load and infectious virus levels in the lung compared to a control mAb. Taken together, these data indicate that VIR-7831 and VIR-7832 are promising new agents in the fight against COVID-19.Competing Interest StatementSome authors are current or former employees of Vir Biotechnology or Humabs BioMed SA (a fully-owned subsidiary of Vir Biotechnology) and may hold shares in Vir Biotechnology. H.W.V. is a founder of PierianDx and Casma Therapeutics. ER -