Portal de Periódicos da CAPES

The SARS-CoV-2 B.1.1.529 Omicron virus causes attenuated infection and disease in mice and hamsters

2021; Research Square (United States); Linguagem: Inglês

10.21203/rs.3.rs-1211792/v1

Michael Diamond, Peter Halfmann, Tadashi Maemura, Kiyoko Iwatsuki‐Horimoto, Shun Iida, Maki Kiso, Suzanne M. Scheaffer, Tamarand L. Darling, Astha Joshi, Samantha Loeber, Stephanie L. Foster, Baoling Ying, Bradley Whitener, Katharine Floyd, Michiko Ujie, Noriko Nakajima, Mutsumi Ito, Ryan Wright, Ryuta Uraki, Rong Li, Yuko Sakai, Yanan Liu, Deanna Larson, Jorge E. Osorio, Juan P. Hernández-Ortíz, Karl Čiuoderis, Kelsey R. Florek, Mit Patel, Allen C. Bateman, Abby Odle, Lok-Yin Roy Wong, Zhongde Wang, Venkata Viswanadh Edara, Zhenlu Chong, 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, Yoshihiro Kawaoka, Daniel C. Douek, Juan I. Moliva, Nancy J. Sullivan, Matthew Gagné, Amy Ransier, James Brett Case, Trushar Jeevan, John Franks, Thomas Fabrizio, Jennifer DeBeauchamp, Lisa Kercher, Patrick Seiler, Gagandeep Singh, Prajakta Warang, Ana S. González-Reiche, Emilia Mia Sordillo, Harm van Bakel, Viviana Simon,

SARS-CoV-2 detection and testing

Abstract Despite the development and deployment of antibody and vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike protein jeopardize their efficacy. The recent emergence of B.1.1.529, the Omicron variant1,2, which has more than 30 mutations in the spike protein, has raised concerns for escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in pre-clinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of multiple B.1.1.529 Omicron isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2) expressing mice and hamsters. Despite modeling and binding data suggesting that B.1.1.529 spike can bind more avidly to murine ACE2, we observed attenuation of infection in 129, C57BL/6, and BALB/c mice as compared with previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. Although K18-hACE2 transgenic mice sustained infection in the lungs, these animals did not lose weight. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease, and pathology with B.1.1.529 also were milder compared to historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from multiple independent laboratories of the SAVE/NIAID network with several different B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.