The Therapeutic Monoclonal Antibody Bamlanivimab Does Not Enhance SARS-CoV-2 Infection by FcR-Mediated Mechanisms
Robert W. Cross,
Christopher M. Wiethoff,
Patricia Brown-Augsburger,
Shawn Berens,
Jamie Blackbourne,
Ling Liu,
Xiaohua Wu,
Jonathan Tetreault,
Carter Dodd,
Ramtin Sina,
Derrick R. Witcher,
Deanna Newcomb,
Denzil Frost,
Angela Wilcox,
Viktoriya Borisevich,
Krystle N. Agans,
Courtney Woolsey,
Abhishek N. Prasad,
Daniel J. Deer,
Joan B. Geisbert,
Natalie S. Dobias,
Karla A. Fenton,
Beth Strifler,
Philip Ebert,
Richard Higgs,
Anne Beall,
Sumit Chanda,
Laura Riva,
Xin Yin,
Thomas W. Geisbert
Affiliations
Robert W. Cross
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Christopher M. Wiethoff
Eli Lilly and Company, Indianapolis, IN 46285, USA
Patricia Brown-Augsburger
Eli Lilly and Company, Indianapolis, IN 46285, USA
Shawn Berens
Eli Lilly and Company, Indianapolis, IN 46285, USA
Jamie Blackbourne
Eli Lilly and Company, Indianapolis, IN 46285, USA
Ling Liu
Eli Lilly and Company, Indianapolis, IN 46285, USA
Xiaohua Wu
Eli Lilly and Company, Indianapolis, IN 46285, USA
Jonathan Tetreault
Eli Lilly and Company, Indianapolis, IN 46285, USA
Carter Dodd
Eli Lilly and Company, Indianapolis, IN 46285, USA
Ramtin Sina
Eli Lilly and Company, Indianapolis, IN 46285, USA
Derrick R. Witcher
Eli Lilly and Company, Indianapolis, IN 46285, USA
Deanna Newcomb
Charles River Laboratories, Inc., Reno, NV 89511, USA
Denzil Frost
Charles River Laboratories, Inc., Reno, NV 89511, USA
Angela Wilcox
Charles River Laboratories, Inc., Reno, NV 89511, USA
Viktoriya Borisevich
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Krystle N. Agans
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Courtney Woolsey
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Abhishek N. Prasad
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Daniel J. Deer
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Joan B. Geisbert
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Natalie S. Dobias
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Karla A. Fenton
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Beth Strifler
Eli Lilly and Company, Indianapolis, IN 46285, USA
Philip Ebert
Eli Lilly and Company, Indianapolis, IN 46285, USA
Richard Higgs
Eli Lilly and Company, Indianapolis, IN 46285, USA
Anne Beall
Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Sumit Chanda
Department of Immunology and Microbiology, Scripps Research, La Jolla, CA 92037, USA
Laura Riva
Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Xin Yin
Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Thomas W. Geisbert
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
As part of the non-clinical safety package characterizing bamlanivimab (SARS-CoV-2 neutralizing monoclonal antibody), the risk profile for antibody-dependent enhancement of infection (ADE) was evaluated in vitro and in an African green monkey (AGM) model of COVID-19. In vitro ADE assays in primary human macrophage, Raji, or THP-1 cells were used to evaluate enhancement of viral infection. Bamlanivimab binding to C1q, FcR, and cell-based effector activity was also assessed. In AGMs, the impact of bamlanivimab pretreatment on viral loads and clinical and histological pathology was assessed to evaluate enhanced SARS-CoV-2 replication or pathology. Bamlanivimab did not increase viral replication in vitro, despite a demonstrated effector function. In vivo, no significant differences were found among the AGM groups for weight, temperature, or food intake. Treatment with bamlanivimab reduced viral loads in nasal and oral swabs and BAL fluid relative to control groups. Viral antigen was not detected in lung tissue from animals treated with the highest dose of bamlanivimab. Bamlanivimab did not induce ADE of SARS-CoV-2 infection in vitro or in an AGM model of infection at any dose evaluated. The findings suggest that high-affinity monoclonal antibodies pose a low risk of mediating ADE in patients and support their safety profile as a treatment of COVID-19 disease.
