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

Peter J. Halfmann, Shun Iida, Kiyoko Iwatsuki-Horimoto, Tadashi Maemura, Maki Kiso, Suzanne M. Scheaffer, Tamarand L. Darling, Astha Joshi, Samantha Loeber, Gagandeep Singh, Stephanie L. Foster, Baoling Ying, James Brett Case, Zhenlu Chong, Bradley Whitener, Juan Moliva, Katharine Floyd, Michiko Ujie, Noriko Nakajima, Mutsumi Ito, Ryan Wright, Ryuta Uraki, Prajakta Warang, Matthew Gagne, Rong Li, Yuko Sakai-Tagawa, Yanan Liu, Deanna Larson, Jorge E. Osorio, Juan P. Hernandez-Ortiz, Amy R. Henry, Karl Ciuoderis, Kelsey R. Florek, Mit Patel, Abby Odle, Lok-Yin Roy Wong, Allen C. Bateman, Zhongde Wang, Venkata-Viswanadh Edara, Zhenlu Chong, John Franks, Trushar Jeevan, Thomas Fabrizio, Jennifer DeBeauchamp, Lisa Kercher, Patrick Seiler, Ana Silvia Gonzalez-Reiche, Emilia Mia Sordillo, Lauren A. Chang, Harm Bakel, Viviana Simon, Daniel C. Douek, Nancy J. Sullivan, Larissa B. Thackray, Hiroshi Ueki, Seiya Yamayoshi, Masaki Imai, Stanley Perlman, Richard J. Webby, Robert A. Seder, Mehul S. Suthar, Adolfo García-Sastre, Michael Schotsaert, Tadaki Suzuki, Adrianus C. M. Boon (), Michael S. Diamond () and Yoshihiro Kawaoka ()
Additional contact information
Peter J. Halfmann: University of Wisconsin-Madison
Shun Iida: National Institute of Infectious Diseases
Kiyoko Iwatsuki-Horimoto: Institute of Medical Science, University of Tokyo
Tadashi Maemura: University of Wisconsin-Madison
Maki Kiso: Institute of Medical Science, University of Tokyo
Suzanne M. Scheaffer: Washington University School of Medicine
Tamarand L. Darling: Washington University School of Medicine
Astha Joshi: Washington University School of Medicine
Samantha Loeber: University of Wisconsin–Madison
Gagandeep Singh: Icahn School of Medicine at Mount Sinai
Stephanie L. Foster: Emory University School of Medicine
Baoling Ying: Washington University School of Medicine
James Brett Case: Washington University School of Medicine
Zhenlu Chong: Washington University School of Medicine
Bradley Whitener: Washington University School of Medicine
Juan Moliva: National Institutes of Health
Katharine Floyd: Emory University School of Medicine
Michiko Ujie: Institute of Medical Science, University of Tokyo
Noriko Nakajima: National Institute of Infectious Diseases
Mutsumi Ito: Institute of Medical Science, University of Tokyo
Ryan Wright: University of Wisconsin-Madison
Ryuta Uraki: Institute of Medical Science, University of Tokyo
Prajakta Warang: Icahn School of Medicine at Mount Sinai
Matthew Gagne: National Institutes of Health
Rong Li: Utah State University
Yuko Sakai-Tagawa: Institute of Medical Science, University of Tokyo
Yanan Liu: Utah State University
Deanna Larson: Utah State University
Jorge E. Osorio: University of Wisconsin
Juan P. Hernandez-Ortiz: Universidad Nacional de Colombia
Amy R. Henry: National Institutes of Health
Karl Ciuoderis: Universidad Nacional de Colombia
Kelsey R. Florek: Wisconsin State Laboratory of Hygiene
Mit Patel: Emory University School of Medicine
Abby Odle: University of Iowa
Lok-Yin Roy Wong: University of Iowa
Allen C. Bateman: Wisconsin State Laboratory of Hygiene
Zhongde Wang: Utah State University
Venkata-Viswanadh Edara: Emory University School of Medicine
Zhenlu Chong: Washington University School of Medicine
John Franks: St Jude Children’s Research Hospital
Trushar Jeevan: St Jude Children’s Research Hospital
Thomas Fabrizio: St Jude Children’s Research Hospital
Jennifer DeBeauchamp: St Jude Children’s Research Hospital
Lisa Kercher: St Jude Children’s Research Hospital
Patrick Seiler: St Jude Children’s Research Hospital
Ana Silvia Gonzalez-Reiche: Icahn School of Medicine at Mount Sinai
Emilia Mia Sordillo: Icahn School of Medicine at Mount Sinai
Lauren A. Chang: Icahn School of Medicine at Mount Sinai
Harm Bakel: Icahn School of Medicine at Mount Sinai
Viviana Simon: Icahn School of Medicine at Mount Sinai
Daniel C. Douek: National Institutes of Health
Nancy J. Sullivan: National Institutes of Health
Larissa B. Thackray: Washington University School of Medicine
Hiroshi Ueki: Institute of Medical Science, University of Tokyo
Seiya Yamayoshi: Institute of Medical Science, University of Tokyo
Masaki Imai: Institute of Medical Science, University of Tokyo
Stanley Perlman: University of Iowa
Richard J. Webby: St Jude Children’s Research Hospital
Robert A. Seder: National Institutes of Health
Mehul S. Suthar: Emory University School of Medicine
Adolfo García-Sastre: Icahn School of Medicine at Mount Sinai
Michael Schotsaert: Icahn School of Medicine at Mount Sinai
Tadaki Suzuki: National Institute of Infectious Diseases
Adrianus C. M. Boon: Washington University School of Medicine
Michael S. Diamond: Washington University School of Medicine
Yoshihiro Kawaoka: University of Wisconsin-Madison

Nature, 2022, vol. 603, issue 7902, 687-692

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41586-022-04441-6

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