| First Author | Nakandakari-Higa S | Year | 2022 |
| Journal | Front Immunol | Volume | 13 |
| Pages | 1007080 | PubMed ID | 36451809 |
| Mgi Jnum | J:335150 | Mgi Id | MGI:7397518 |
| Doi | 10.3389/fimmu.2022.1007080 | Citation | Nakandakari-Higa S, et al. (2022) A minimally-edited mouse model for infection with multiple SARS-CoV-2 strains. Front Immunol 13:1007080 |
| abstractText | Efficient mouse models to study SARS-CoV-2 infection are critical for the development and assessment of vaccines and therapeutic approaches to mitigate the current pandemic and prevent reemergence of COVID-19. While the first generation of mouse models allowed SARS-CoV-2 infection and pathogenesis, they relied on ectopic expression and non-physiological levels of human angiotensin-converting enzyme 2 (hACE2). Here we generated a mouse model carrying the minimal set of modifications necessary for productive infection with multiple strains of SARS-CoV-2. Substitution of only three amino acids in the otherwise native mouse Ace2 locus (Ace2 (TripleMutant) or Ace2), was sufficient to render mice susceptible to both SARS-CoV-2 strains USA-WA1/2020 and B.1.1.529 (Omicron). Infected Ace2 mice exhibited weight loss and lung damage and inflammation, similar to COVID-19 patients. Previous exposure to USA-WA1/2020 or mRNA vaccination generated memory B cells that participated in plasmablast responses during breakthrough B.1.1.529 infection. Thus, the Ace2 mouse replicates human disease after SARS-CoV-2 infection and provides a tool to study immune responses to sequential infections in mice. |
