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An ADAM17-Neutralizing Antibody Reduces Inflammation and Mortality While Increasing Viral Burden in a COVID-19 Mouse
Jodi F Hedges1, Deann T Snyder1, Amanda Robison1
1Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States.
Frontiers in Immunology
|June 27, 2022
Summary
Blocking ADAM17 (A disintegrin and metalloproteinase 17) improved COVID-19 mouse health and reduced lung damage. However, this blockade also increased viral load, suggesting a complex role in SARS-CoV-2 infection.
Area of Science:
- Virology
- Immunology
- Biochemistry
Background:
- Angiotensin Converting Enzyme 2 (ACE2) is essential for SARS-CoV and SARS-CoV-2 entry.
- A disintegrin and metalloproteinase 17 (ADAM17) cleaves cell surface proteins like ACE2 and TNF-α.
Purpose of the Study:
- To investigate the role of ADAM17 in COVID-19 pathogenesis.
- To assess the therapeutic potential of blocking ADAM17 activity.
Main Methods:
- Utilized the K18-hACE2 transgenic mouse model for COVID-19.
- Administered MEDI3622, a monoclonal antibody targeting ADAM17.
- Compared outcomes between antibody-treated and saline-treated groups.
Main Results:
- MEDI3622 treatment led to healthier mice with reduced lung pathology.
- Viral burden in the lungs was significantly increased in antibody-treated mice.
- ADAM17 inhibition showed a dual effect: reduced inflammation but increased viral load.
Conclusions:
- ADAM17 plays a critical role in controlling viral replication.
- ADAM17 also contributes to inflammatory damage in COVID-19.
- MEDI3622 antibody may have therapeutic applications by modulating the inflammatory cascade.
