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

Peter Halfmann(University of Wisconsin–Madison), Shun Iida(National Institute of Infectious Diseases), Kiyoko Iwatsuki‐Horimoto(Tokyo University of Science), Tadashi Maemura(University of Wisconsin–Madison), Maki Kiso(Tokyo University of Science), Suzanne M. Scheaffer(Washington University in St. Louis), Tamarand L. Darling(Washington University in St. Louis), Astha Joshi(Washington University in St. Louis), Samantha Loeber(University of Wisconsin–Madison), Gagandeep Singh(Icahn School of Medicine at Mount Sinai), Stephanie L. Foster(Emory University), Baoling Ying(Washington University in St. Louis), James Brett Case(Washington University in St. Louis), Zhenlu Chong(Washington University in St. Louis), Bradley Whitener(Washington University in St. Louis), Juan I. Moliva(National Institutes of Health), Katharine Floyd(Emory University), Michiko Ujie(Tokyo University of Science), Noriko Nakajima(National Institute of Infectious Diseases), Mutsumi Ito(Tokyo University of Science), Ryan Wright(University of Wisconsin–Madison), Ryuta Uraki(Tokyo University of Science), Prajakta Warang(Icahn School of Medicine at Mount Sinai), Matthew Gagné(National Institutes of Health), Rong Li(Utah State University), Yuko Sakai‐Tagawa(Tokyo University of Science), Yanan Liu(Utah State University), Deanna Larson(Utah State University), Jorge E. Osorio(University of Wisconsin–Madison), Juan P. Hernández-Ortíz(Universidad Nacional de Colombia), Amy R. Henry(National Institutes of Health), Karl Čiuoderis(Universidad Nacional de Colombia), Kelsey R. Florek, Mit Patel(Emory University), Abby Odle(University of Iowa), Lok-Yin Roy Wong(University of Iowa), Allen Bateman, Zhongde Wang(Utah State University), Venkata Viswanadh Edara(Emory University), Zhenlu Chong(Washington University in St. Louis), 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 S. 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 van Bakel(Icahn School of Medicine at Mount Sinai), Viviana Simon(Icahn School of Medicine at Mount Sinai), Bremy Alburquerque(Icahn School of Medicine at Mount Sinai), Hala Alshammary(Icahn School of Medicine at Mount Sinai), Angela A. Amoako(Icahn School of Medicine at Mount Sinai), Sadaf Aslam(Icahn School of Medicine at Mount Sinai), Radhika Banu(Icahn School of Medicine at Mount Sinai), Christian Cognigni(Icahn School of Medicine at Mount Sinai), Marlene Espinoza‐Moraga(Icahn School of Medicine at Mount Sinai), Keith Farrugia(Icahn School of Medicine at Mount Sinai), Adriana van de Guchte(Icahn School of Medicine at Mount Sinai), Zain Khalil(Icahn School of Medicine at Mount Sinai), Manon Laporte(Icahn School of Medicine at Mount Sinai), Ignacio Mena(Icahn School of Medicine at Mount Sinai), Alberto Paniz‐Mondolfi(Icahn School of Medicine at Mount Sinai), J. Polanco(Icahn School of Medicine at Mount Sinai), Aria Rooker(Icahn School of Medicine at Mount Sinai), Levy A. Sominsky(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 in St. Louis), Hiroshi Ueki(Tokyo University of Science), Seiya Yamayoshi(Tokyo University of Science), Masaki Imai(Tokyo University of Science), 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), 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 in St. Louis), Michael Diamond(Washington University in St. Louis), Yoshihiro Kawaoka(University of Wisconsin–Madison)
Nature
January 21, 2022
10.1038/s41586-022-04441-6
Cited by 696Open Access
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Abstract

Abstract The recent emergence of B.1.1.529, the Omicron variant 1,2 , 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.

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