Author:
Nakandakari-Higa Sandra,Parsa Roham,Reis Bernardo S.,de Carvalho Renan V. H.,Mesin Luka,Hoffmann Hans-Heinrich,Bortolatto Juliana,Muramatsu Hiromi,Lin Paulo. J. C.,Bilate Angelina M.,Rice Charles M.,Pardi Norbert,Mucida Daniel,Victora Gabriel D.,Canesso Maria Cecilia C.
Abstract
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 (Ace2TripleMutant 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.
Subject
Immunology,Immunology and Allergy
Cited by
4 articles.
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