SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters

Author:

Halfmann Peter J.,Iida ShunORCID,Iwatsuki-Horimoto KiyokoORCID,Maemura Tadashi,Kiso Maki,Scheaffer Suzanne M.,Darling Tamarand L.,Joshi AsthaORCID,Loeber Samantha,Singh GagandeepORCID,Foster Stephanie L.ORCID,Ying Baoling,Case James BrettORCID,Chong Zhenlu,Whitener BradleyORCID,Moliva Juan,Floyd KatharineORCID,Ujie Michiko,Nakajima Noriko,Ito Mutsumi,Wright Ryan,Uraki RyutaORCID,Warang Prajakta,Gagne Matthew,Li Rong,Sakai-Tagawa Yuko,Liu Yanan,Larson Deanna,Osorio Jorge E.,Hernandez-Ortiz Juan P.ORCID,Henry Amy R.,Ciuoderis Karl,Florek Kelsey R.ORCID,Patel Mit,Odle Abby,Wong Lok-Yin Roy,Bateman Allen C.,Wang ZhongdeORCID,Edara Venkata-ViswanadhORCID,Chong Zhenlu,Franks John,Jeevan Trushar,Fabrizio ThomasORCID,DeBeauchamp Jennifer,Kercher Lisa,Seiler Patrick,Gonzalez-Reiche Ana SilviaORCID,Sordillo Emilia MiaORCID,Chang Lauren A.ORCID,van Bakel HarmORCID,Simon VivianaORCID,Alburquerque B.,Alshammary H.,Amoako A. A.,Aslam S.,Banu R.,Cognigni C.,Espinoza-Moraga M.,Farrugia K.,van de Guchte A.,Khalil Z.,Laporte M.,Mena I.,Paniz-Mondolfi A. E.,Polanco J.,Rooker A.,Sominsky L. A.,Douek Daniel C.,Sullivan Nancy J.,Thackray Larissa B.ORCID,Ueki HiroshiORCID,Yamayoshi SeiyaORCID,Imai MasakiORCID,Perlman StanleyORCID,Webby Richard J.ORCID,Seder Robert A.ORCID,Suthar Mehul S.,García-Sastre AdolfoORCID,Schotsaert MichaelORCID,Suzuki TadakiORCID,Boon Adrianus C. M.ORCID,Diamond Michael S.ORCID,Kawaoka YoshihiroORCID,

Abstract

AbstractThe 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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases

Division of Intramural Research, National Institute of Allergy and Infectious Diseases

U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Helen Hay Whitney Foundation

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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