Abstract
Efficacious interventions are urgently needed for the treatment of COVID-19. Here, we report a monoclonal antibody (mAb), MW05, with SARS-CoV-2 neutralizing activity by disrupting the interaction of receptor binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) receptor. Crosslinking of Fc with FcγRIIB mediates antibody-dependent enhancement (ADE) activity by MW05. This activity is eliminated by introducing the LALA mutation to the Fc region (MW05/LALA). Potent prophylactic and therapeutic effects against SARS-CoV-2 are observed in rhesus monkeys. A single dose of MW05/LALA blocks infection of SARS-CoV-2 in prophylactic treatment and clears SARS-CoV-2 in three days in a therapeutic treatment setting. These results pave the way for the development of MW05/LALA as an antiviral strategy for COVID-19.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin-Converting Enzyme 2
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Animals
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Antibodies, Monoclonal / immunology*
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Antibodies, Neutralizing / immunology*
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Antibodies, Viral / immunology
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Antiviral Agents / pharmacology*
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Betacoronavirus / immunology*
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COVID-19
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Cell Line
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Chlorocebus aethiops
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Coronavirus Infections / prevention & control
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Coronavirus Infections / therapy*
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Female
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HEK293 Cells
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Humans
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Macaca mulatta
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Male
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Pandemics / prevention & control
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Peptidyl-Dipeptidase A / metabolism
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Pneumonia, Viral / prevention & control
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Pneumonia, Viral / therapy*
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Receptors, IgG / genetics
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Receptors, IgG / immunology
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Receptors, Virus / metabolism
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SARS-CoV-2
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Spike Glycoprotein, Coronavirus / immunology*
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Vero Cells
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Virus Attachment
Substances
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Antibodies, Monoclonal
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Antibodies, Neutralizing
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Antibodies, Viral
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Antiviral Agents
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FCGR2B protein, human
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Receptors, IgG
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Receptors, Virus
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Spike Glycoprotein, Coronavirus
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spike protein, SARS-CoV-2
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Peptidyl-Dipeptidase A
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2