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

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.

SUBMITTER: Diamond M

PROVIDER: S-EPMC8722607 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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

Diamond Michael M Halfmann Peter P Maemura Tadashi T Iwatsuki-Horimoto Kiyoko K Iida Shun S Kiso Maki M Scheaffer Suzanne S Darling Tamarand T Joshi Astha A Loeber Samantha S Foster Stephanie S Ying Baoling B Whitener Bradley B Floyd Katharine K Ujie Michiko M Nakajima Noriko N Ito Mutsumi M Wright Ryan R Uraki Ryuta R Li Rong R Sakai Yuko Y Liu Yanan Y Larson Deanna D Osorio Jorge J Hernandez-Ortiz Juan J Čiuoderis Karl K Florek Kelsey K Patel Mit M Bateman Allen A Odle Abby A Wong Lok-Yin LY Wang Zhongde Z Edara Venkata Viswanadh VV Chong Zhenlu Z Thackray Larissa L Ueki Hiroshi H Yamayoshi Seiya S Imai Masaki M Perlman Stanley S Webby Richard R Seder Robert R Suthar Mehul M Garcia-Sastre Adolfo A Schotsaert Michael M Suzuki Tadaki T Boon Adrianus A Kawaoka Yoshihiro Y Douek Daniel D Moliva Juan J Sullivan Nancy N Gagne Matthew M Ransier Amy A Case James J Jeevan Trushar T Franks John J Fabrizio Thomas T DeBeauchamp Jennifer J Kercher Lisa L Seiler Patrick P Singh Gagandeep G Warang Prajakta P Gonzalez-Reiche Ana S AS Sordillo Emilia E van Bakel Harm H Simon Viviana V

Research square 20211229

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 ro ...[more]

PMID: 34981044

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Project description:White-tailed deer ( Odocoileus virginianus ) are highly susceptible to infection by SARS-CoV-2, with multiple reports of widespread spillover of virus from humans to free-living deer. While the recently emerged SARS-CoV-2 B.1.1.529 Omicron variant of concern (VoC) has been shown to be notably more transmissible amongst humans, its ability to cause infection and spillover to non-human animals remains a challenge of concern. We found that 19 of the 131 (14.5%; 95% CI: 0.10-0.22) white-tailed deer opportunistically sampled on Staten Island, New York, between December 12, 2021, and January 31, 2022, were positive for SARS-CoV-2 specific serum antibodies using a surrogate virus neutralization assay, indicating prior exposure. The results also revealed strong evidence of age-dependence in antibody prevalence. A significantly (χ 2 , p < 0.001) greater proportion of yearling deer possessed neutralizing antibodies as compared with fawns (OR=12.7; 95% CI 4-37.5). Importantly, SARS-CoV-2 nucleic acid was detected in nasal swabs from seven of 68 (10.29%; 95% CI: 0.0-0.20) of the sampled deer, and whole-genome sequencing identified the SARS-CoV-2 Omicron VoC (B.1.1.529) is circulating amongst the white-tailed deer on Staten Island. Phylogenetic analyses revealed the deer Omicron sequences clustered closely with other, recently reported Omicron sequences recovered from infected humans in New York City and elsewhere, consistent with human to deer spillover. Interestingly, one individual deer was positive for viral RNA and had a high level of neutralizing antibodies, suggesting either rapid serological conversion during an ongoing infection or a "breakthrough" infection in a previously exposed animal. Together, our findings show that the SARS-CoV-2 B.1.1.529 Omicron VoC can infect white-tailed deer and highlights an urgent need for comprehensive surveillance of susceptible animal species to identify ecological transmission networks and better assess the potential risks of spillback to humans.Key findingsThese studies provide strong evidence of infection of free-living white-tailed deer with the SARS-CoV-2 B.1.1.529 Omicron variant of concern on Staten Island, New York, and highlight an urgent need for investigations on human-to-animal-to-human spillovers/spillbacks as well as on better defining the expanding host-range of SARS-CoV-2 in non-human animals and the environment.

Dataset Information

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

Publications

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

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