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 Prasad, Daniel J. Deer, Joan B. GeisbertNatalie S. Dobias, Karla Fenton, Beth Strifler, Philip Ebert, Richard Higgs, Anne Beall, Sumit Chanda, Laura Riva, Xin Yin, Thomas W. Geisbert

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1408
JournalPathogens
Volume12
Issue number12
DOIs
StatePublished - Dec 2023

Keywords

  • antibody-dependent enhancement
  • bamlanivimab
  • COVID-19
  • monoclonal antibodies
  • SARS-CoV-2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • General Immunology and Microbiology
  • Microbiology (medical)
  • Infectious Diseases

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