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

• Type of Material: Article
• Authors: Peter J Halfmann, University of Wisconsin-Madison; Shun Iida, National Institute of Infectious Diseases; Kiyoko Iwatsuki-Horimoto, University of Tokyo; Tadashi Maemura, University of Wisconsin-Madison; Maki Kiso, 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; 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 Institute of Allergy and Infectious Diseases; Katharine Floyd, Emory University; Michiko Ujie, University of Tokyo; Noriko Nakajima, National Institute of Infectious Diseases, Tokyo; Mutsumi Ito, University of Tokyo; Ryan Wright, Univ Wisconsin; Ryuta Uraki, University of Tokyo; Prajakta Warang, Icahn School of Medicine at Mount Sinai; Matthew Gagne, National Institute of Allergy and Infectious Diseases; Rong Li, Utah State University; Yuko Sakai-Tagawa, University of Tokyo; Yanan Liu, Utah State University; Deanna Larson, Utah State University; Jorge E Osorio, University of Wisconsin, Madison; Juan P Hernandez-Ortiz, Universidad Nacional de Colombia; Amy R Henry, National Institute of Allergy and Infectious Diseases; Karl Ciuoderis, Universidad Nacional de Colombia; Kelsey R Florek, Wisconsin State Laboratory of Hygiene; Mit Patel, Emory University; 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-Viswanaddh Edara, Emory University; Zhenlu Chong, Utah State University; John Franks, Utah State University; 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 M Sordillo, Icahn School of Medicine at Mount Sinai; Lauren A Chang, Icahn School of Medicine at Mount Sinai; Harm van Baker, Icahn School of Medicine at Mount Sinai; Viviana Simon, Icahn School of Medicine at Mount Sinai; Daniel C Douek, National Institute of Allergy and Infectious Diseases; Nancy J Sullivan, National Institute of Allergy and Infectious Diseases; Larissa B Thackray, Washington University School of Medicine; Hiroshi Ueki, University of Tokyo; Seiya Yamayoshi, University of Tokyo; Masaki Imai, University of Tokyo; Stanley Perlman, University of Iowa; Richard J Webby, St Jude Childrens Research Hospital; Robert A Seder, National Institute of Allergy and Infectious Diseases; Mehul Suthar, Emory University; 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, Tokyo; Adrianus CM Boon, Washington University; Michael S Diamond, Washington University; Yoshihiro Kawaoka, University of Wisconsin-Madison
• Language: English
• Date: 2022-01-21
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41586-022-04441-6
• Title of Journal or Parent Work: NATURE
• Volume: 603
• Issue: 7902
• Start Page: 687
• End Page: +
• Grant/Funding Information: This study was supported by grants and contracts from the NIH (R01 AI157155 (M.S.D.), U01 AI151810 (M.S.D. and A.C.M.B.), 75N93021C00014 (Center for Research on Influenza Pathogenesis and Transmission; Y.K. and A.G.-S.), HHSN272201400008C (Y.K.), HHSN272201700041I (Z.W.), 75N93020F00001/A38 (Z.W.), P51OD011132 (M.S.S.), R56AI147623 (M.S.S.), HHSN272201400004C (M.S.S.), 75N93021C00017 (M.S.S.), P01 AI060699 (S.P.), R01 AI129269 (S.P.), R01DK130425 (M.S.), 5T32AI007647-22 (L.A.C.), 75N93019C00051 (M.S.D.) and 75N93021C00016 (St Jude Center of Excellence on Influenza Research and Response; R.J.W. and A.C.M.B.)), as well as grants from the Defense Advanced Research Projects Agency (HR0011-19-2-319 0020 (A.G.-S.)), and the Research Program on Emerging and Re-emerging Infectious Diseases (JP20fk0108412, JP21fk0108615, JP20fk0108472 and JP21fk0108104), a Project Promoting Support for Drug Discovery (JP20nk0101632) and the Japan Program for Infectious Diseases Research and Infrastructure (JP21wm0125002) from the Japan Agency for Medical Research and Development (AMED). The Woodruff Health Sciences Center and Emory School of Medicine, Woodruff Health Sciences Center 2020 COVID-19 CURE Award, and the Intramural programme of the NIAID, NIH (D.C.D., R.A.S. and N.J.S.) also supported this study. The piggyBac vector, pmhyGEMIE-3, was a gift from S. Moisyadi at the University of Hawaii. The Mount Sinai Pathogen Surveillance (E.M.S., H.v.B. and V.S.) is supported by institutional school and hospital funds as well as by an option to 75N93021C00014 (A.G.-S.). We thank R. Albrecht for support with the biosafety level 3 facility and procedures at the Icahn School of Medicine at Mount Sinai, New York.
• Keywords: BAD; Science & Technology - Other Topics; NEUTRALIZING ANTIBODIES; Science & Technology; Multidisciplinary Sciences; INFECTION
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery; Biology, Microbiology; Health Sciences, Pathology

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.