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The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2
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 Jr.; Arnold Park; Elisabetta Cameroni; Sarah Ledoux; Adam Werts; Christophe Colas; Leah Soriaga; Amalio Telenti; Lisa A Purcell; Seungmin Hwang; Gyorgy Snell; Herbert W Virgin; Davide Corti; Christy M Hebner.
  • Andrea L Cathcart; Vir Biotechnology
  • Colin Havenar-Daughton; Vir Biotechnology
  • Florian A Lempp; Vir Biotechnology
  • Daphne Ma; Vir Biotechnology
  • Michael Schmid; Vir Biotechnology
  • Maria L Agostini; Vir Biotechnology
  • Barbara Guarino; Humabs Biomed SA, a subsidiary of Vir Biotechnology
  • Julia Di iulio; Vir Biotechnology
  • Laura Rosen; Vir Biotechnology
  • Heather Tucker; Vir Biotechnology
  • Joshua Dillen; Vir Biotechnology
  • Sambhavi Subramanian; Vir Biotechnology
  • Barbara Sloan; Vir Biotechnology
  • Siro Bianchi; Humabs Biomed SA, a subsidiary of Vir Biotechnology
  • Jason Wojcechowskyj; Vir Biotechnology
  • Jiayi Zhou; Vir Biotechnology
  • Hannah Kaiser; Vir Biotechnology
  • Arthur Chase; Vir Biotechnology
  • Elvin Lauron; Vir Biotechnology
  • Martin Montiel-Ruiz; Vir Biotechnology
  • Roberto Spreafico; Vir Biotechnology
  • Julia Noack; Vir Biotechnology
  • Nadine Czudnochowski; Vir Biotechnology
  • Anna Sahakyan; Vir Biotechnology
  • Dora Pinto; Humabs Biomed SA
  • Christian Saliba; Humabs Biomed SA
  • Katja Culap; Humabs Biomed SA, a subsidiary of Vir Biotechnology
  • Exequiel Delotta Jr.; Vir Biotechnology
  • Arnold Park; Vir Biotechnology
  • Elisabetta Cameroni; Humabs Biomed SA, a subsidiary of Vir Biotechnology
  • Sarah Ledoux; Vir Biotechnology
  • Adam Werts; Lovelace Biomedical
  • Christophe Colas; Vir Biotechnology
  • Leah Soriaga; Vir Biotechnology
  • Amalio Telenti; Vir Biotechnology
  • Lisa A Purcell; Vir Biotechnology
  • Seungmin Hwang; Vir Biotechnology
  • Gyorgy Snell; Vir Biotechnology
  • Herbert W Virgin; Vir Biotechnology
  • Davide Corti; Humabs Biomed SA, a subsidiary of Vir Biotechnology
  • Christy M Hebner; Vir Biotechnology
Preprint in English | bioRxiv | ID: ppbiorxiv-434607
ABSTRACT
VIR-7831 (sotrovimab) 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. 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 including the Omicron variant. In addition, they retain activity against monoclonal antibody resistance mutations conferring reduced susceptibility to currently authorized mAbs. The VIR-7831/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 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 key agents in the fight against COVID-19.
Full text: Available Collection: Preprints Database: bioRxiv Document Type: Preprint Language: English Year: 2021

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Full text: Available Collection: Preprints Database: bioRxiv Document Type: Preprint Language: English Year: 2021
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