TY - JOUR
T1 - The Therapeutic Monoclonal Antibody Bamlanivimab Does Not Enhance SARS-CoV-2 Infection by FcR-Mediated Mechanisms
AU - Cross, Robert W.
AU - Wiethoff, Christopher M.
AU - Brown-Augsburger, Patricia
AU - Berens, Shawn
AU - Blackbourne, Jamie
AU - Liu, Ling
AU - Wu, Xiaohua
AU - Tetreault, Jonathan
AU - Dodd, Carter
AU - Sina, Ramtin
AU - Witcher, Derrick R.
AU - Newcomb, Deanna
AU - Frost, Denzil
AU - Wilcox, Angela
AU - Borisevich, Viktoriya
AU - Agans, Krystle N.
AU - Woolsey, Courtney
AU - Prasad, Abhishek
AU - Deer, Daniel J.
AU - Geisbert, Joan B.
AU - Dobias, Natalie S.
AU - Fenton, Karla
AU - Strifler, Beth
AU - Ebert, Philip
AU - Higgs, Richard
AU - Beall, Anne
AU - Chanda, Sumit
AU - Riva, Laura
AU - Yin, Xin
AU - Geisbert, Thomas W.
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - antibody-dependent enhancement
KW - bamlanivimab
KW - COVID-19
KW - monoclonal antibodies
KW - SARS-CoV-2
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U2 - 10.3390/pathogens12121408
DO - 10.3390/pathogens12121408
M3 - Article
AN - SCOPUS:85180478230
SN - 2076-0817
VL - 12
JO - Pathogens
JF - Pathogens
IS - 12
M1 - 1408
ER -