The Therapeutic Monoclonal Antibody Bamlanivimab Does Not Enhance SARS-CoV-2 Infection by FcR-Mediated Mechanisms.

Autor: Cross RW; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA., Wiethoff CM; Eli Lilly and Company, Indianapolis, IN 46285, USA., Brown-Augsburger P; Eli Lilly and Company, Indianapolis, IN 46285, USA., Berens S; Eli Lilly and Company, Indianapolis, IN 46285, USA., Blackbourne J; Eli Lilly and Company, Indianapolis, IN 46285, USA., Liu L; Eli Lilly and Company, Indianapolis, IN 46285, USA., Wu X; Eli Lilly and Company, Indianapolis, IN 46285, USA., Tetreault J; Eli Lilly and Company, Indianapolis, IN 46285, USA., Dodd C; Eli Lilly and Company, Indianapolis, IN 46285, USA., Sina R; Eli Lilly and Company, Indianapolis, IN 46285, USA., Witcher DR; Eli Lilly and Company, Indianapolis, IN 46285, USA., Newcomb D; Charles River Laboratories, Inc., Reno, NV 89511, USA., Frost D; Charles River Laboratories, Inc., Reno, NV 89511, USA., Wilcox A; Charles River Laboratories, Inc., Reno, NV 89511, USA., Borisevich V; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA., Agans KN; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA., Woolsey C; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA., Prasad AN; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA., Deer DJ; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA., Geisbert JB; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA., Dobias NS; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA., Fenton KA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA., Strifler B; Eli Lilly and Company, Indianapolis, IN 46285, USA., Ebert P; Eli Lilly and Company, Indianapolis, IN 46285, USA., Higgs R; Eli Lilly and Company, Indianapolis, IN 46285, USA., Beall A; 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., Chanda S; Department of Immunology and Microbiology, Scripps Research, La Jolla, CA 92037, USA., Riva L; 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., Yin X; 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., Geisbert TW; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA.
Jazyk: angličtina
Zdroj: Pathogens (Basel, Switzerland) [Pathogens] 2023 Nov 30; Vol. 12 (12). Date of Electronic Publication: 2023 Nov 30.
DOI: 10.3390/pathogens12121408
Abstrakt: 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.
Databáze: MEDLINE