A minimally-edited mouse model for infection with multiple SARS-CoV-2 strains

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Developing effective mouse models for SARS-CoV-2 is crucial for vaccine and therapeutic development.
• Previous models often used non-physiological levels of human angiotensin-converting enzyme 2 (hACE2).

Purpose of the Study:

• To create a mouse model with minimal genetic modification for productive SARS-CoV-2 infection.
• To establish a tool for studying COVID-19 pathogenesis and immune responses.

Main Methods:

• Generated a mouse model (Ace2™) by substituting three amino acids in the native mouse Ace2 locus.
• Infected Ace2™ mice with SARS-CoV-2 strains USA-WA1/2020 and B.1.1.529 (Omicron).
• Assessed weight loss, lung damage, inflammation, and immune cell responses.

Main Results:

• Ace2™ mice were susceptible to both SARS-CoV-2 strains, exhibiting weight loss and lung pathology.
• Infected mice showed lung damage and inflammation, mirroring human COVID-19.
• Previous infection or vaccination induced memory B cells that responded during breakthrough Omicron infection.

Conclusions:

• The Ace2™ mouse model accurately replicates human disease following SARS-CoV-2 infection.
• This model serves as a valuable tool for investigating immune responses to sequential SARS-CoV-2 infections and evaluating medical countermeasures.