The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2
By
Andrea L Cathcart,
Colin Havenar-Daughton,
Florian A Lempp,
Daphne Ma,
Michael Schmid,
Maria L Agostini,
Barbara Guarino,
Julia Di iulio,
Laura Rosen,
Heather Tucker,
Joshua Dillen,
Sambhavi Subramanian,
Barbara Sloan,
Siro Bianchi,
Jason Wojcechowskyj,
Jiayi Zhou,
Hannah Kaiser,
Arthur Chase,
Elvin Lauron,
Martin Montiel-Ruiz,
Roberto Spreafico,
Julia Noack,
Nadine Czudnochowski,
Anna Sahakyan,
Dora Pinto,
Christian Saliba,
Katja Culap,
Exequiel Delotta,
Arnold Park,
Elisabetta Cameroni,
Sarah Ledoux,
Yoshihiro Kawaoka,
Adam Werts,
Christophe Colas,
Leah Soriaga,
Amalio Telenti,
Lisa A. Purcell,
Seungmin Hwang,
Gyorgy Snell,
Herbert W Virgin,
Davide Corti,
Christy M Hebner
Posted 10 Mar 2021
bioRxiv DOI: 10.1101/2021.03.09.434607
Sotrovimab (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). Sotrovimab 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. 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. Sotrovimab and VIR-7832 neutralize wild-type and variant pseudotyped viruses and authentic virus in vitro. In addition, they retain activity against monoclonal antibody resistance mutations conferring reduced susceptibility to previously authorized mAbs. The sotrovimab/VIR-7832 epitope 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 sotrovimab 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 sotrovimab and VIR-7832 are key agents in the fight against COVID-19.
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