Dissecting strategies to tune the therapeutic potential of SARS-CoV-2–specific monoclonal antibody CR3022

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  • Atyeo, C.
    • Other Affiliation: MIT
  • Slein, M.D.
    • Other Affiliation: MIT
  • Fischinger, S.
    • Other Affiliation: University of Duisburg-Essen
  • Burke, J.
    • Other Affiliation: MIT
  • Schäfer, A.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Leist, S.R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Kuzmina, N.A.
    • Other Affiliation: University of Texas Medical Branch
  • Mire, C.
    • Other Affiliation: University of Texas Medical Branch
  • Honko, A.
    • Other Affiliation: Boston University School of Medicine
  • Johnson, R.
    • Other Affiliation: Boston University School of Medicine
  • Storm, N.
    • Other Affiliation: Boston University School of Medicine
  • Bernett, M.
    • Other Affiliation: Xencor
  • Tong, P.
    • Other Affiliation: Harvard Medical School
  • Zuo, T.
    • Other Affiliation: Harvard Medical School
  • Lin, J.
    • Other Affiliation: Harvard Medical School
  • Zuiani, A.
    • Other Affiliation: Harvard Medical School
  • Linde, C.
    • Other Affiliation: SeromYx Systems
  • Suscovich, T.
    • Other Affiliation: SeromYx Systems
  • Wesemann, D.R.
    • Other Affiliation: Harvard Medical School
  • Griffiths, A.
    • Other Affiliation: Boston University School of Medicine
  • Desjarlais, J.R.
    • Other Affiliation: Xencor
  • Juelg, B.D.
    • Other Affiliation: MIT
  • Goudsmit, J.
    • Other Affiliation: Harvard T.H. Chan School of Public Health
  • Bukreyev, A.
    • Other Affiliation: University of Texas Medical Branch
  • Baric, R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Alter, G.
    • Other Affiliation: MIT
Abstract
  • The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with a lack of therapeutics, has paralyzed the globe. Although significant effort has been invested in identifying antibodies that block infection, the ability of antibodies to target infected cells through Fc interactions may be vital to eliminate the virus. To explore the role of Fc activity in SARS-CoV-2 immunity, the functional potential of a cross–SARS-reactive antibody, CR3022, was assessed. CR3022 was able to broadly drive antibody effector functions, providing critical immune clearance at entry and upon egress. Using selectively engineered Fc variants, no protection was observed after administration of WT IgG1 in mice or hamsters. Conversely, the functionally enhanced Fc variant resulted in increased pathology in both the mouse and hamster models, causing weight loss in mice and enhanced viral replication and weight loss in the more susceptible hamster model, highlighting the pathological functions of Fc-enhancing mutations. These data point to the critical need for strategic Fc engineering for the treatment of SARS-CoV-2 infection.
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  • Article
Rights statement
  • In Copyright
License
  • Attribution 3.0 United States
Journal title
  • JCI Insight
Journal volume
  • 6
Journal issue
  • 1
Language
  • English
ISSN
  • 2379-3708
Publisher
  • American Society for Clinical Investigation

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