Abstract

The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs. 3,4), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease and pathology with B.1.1.529 were also milder than with historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.

Highlights

  • TI This is a PDF file of a peer-reviewed paper that has been accepted for publication

  • Despite modeling data suggesting that B.1.1.529 spike can bind more avidly to murine ACE23,4, we observed less infection in 129, C57BL/6, BALB/c, and K18

  • In wild-type T and human angiotensin-converting enzyme 2 (ACE2) (hACE2) transgenic hamsters, lung infection, clinical disease, and pathology with AR B.1.1.529 were milder compared to historical isolates or other SARS-CoV-2 variants of concern

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Summary

D Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. TE Consortium Mount Sinai Pathogen Surveillance (PSP) study group A B. Farrugia[17], A. van de Guchte[17], Z. E. Paniz-Mondolfi[18], ACCEL J.

METHODS
Findings
A Syrian R Hamster ACELE 129 mice
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