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.
Original language | English |
---|---|
Pages (from-to) | 687-692 |
Number of pages | 6 |
Journal | Nature |
Volume | 603 |
Issue number | 7902 |
DOIs | |
State | Published - Mar 24 2022 |
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SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters. / Consortium Mount Sinai Pathogen Surveillance (PSP) study group.
In: Nature, Vol. 603, No. 7902, 24.03.2022, p. 687-692.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters
AU - Consortium Mount Sinai Pathogen Surveillance (PSP) study group
AU - Halfmann, Peter J.
AU - Iida, Shun
AU - Iwatsuki-Horimoto, Kiyoko
AU - Maemura, Tadashi
AU - Kiso, Maki
AU - Scheaffer, Suzanne M.
AU - Darling, Tamarand L.
AU - Joshi, Astha
AU - Loeber, Samantha
AU - Singh, Gagandeep
AU - Foster, Stephanie L.
AU - Ying, Baoling
AU - Case, James Brett
AU - Chong, Zhenlu
AU - Whitener, Bradley
AU - Moliva, Juan
AU - Floyd, Katharine
AU - Ujie, Michiko
AU - Nakajima, Noriko
AU - Ito, Mutsumi
AU - Wright, Ryan
AU - Uraki, Ryuta
AU - Warang, Prajakta
AU - Gagne, Matthew
AU - Li, Rong
AU - Sakai-Tagawa, Yuko
AU - Liu, Yanan
AU - Larson, Deanna
AU - Osorio, Jorge E.
AU - Hernandez-Ortiz, Juan P.
AU - Henry, Amy R.
AU - Ciuoderis, Karl
AU - Florek, Kelsey R.
AU - Patel, Mit
AU - Odle, Abby
AU - Wong, Lok Yin Roy
AU - Bateman, Allen C.
AU - Wang, Zhongde
AU - Edara, Venkata Viswanadh
AU - Chong, Zhenlu
AU - Franks, John
AU - Jeevan, Trushar
AU - Fabrizio, Thomas
AU - DeBeauchamp, Jennifer
AU - Kercher, Lisa
AU - Seiler, Patrick
AU - Gonzalez-Reiche, Ana Silvia
AU - Sordillo, Emilia Mia
AU - Chang, Lauren A.
AU - van Bakel, Harm
AU - Simon, Viviana
AU - Alburquerque, B.
AU - Alshammary, H.
AU - Amoako, A. A.
AU - Aslam, S.
AU - Banu, R.
AU - Cognigni, C.
AU - Espinoza-Moraga, M.
AU - Farrugia, K.
AU - van de Guchte, A.
AU - Khalil, Z.
AU - Laporte, M.
AU - Mena, I.
AU - Paniz-Mondolfi, A. E.
AU - Polanco, J.
AU - Rooker, A.
AU - Sominsky, L. A.
AU - Douek, Daniel C.
AU - Sullivan, Nancy J.
AU - Thackray, Larissa B.
AU - Ueki, Hiroshi
AU - Yamayoshi, Seiya
AU - Imai, Masaki
AU - Perlman, Stanley
AU - Webby, Richard J.
AU - Seder, Robert A.
AU - Suthar, Mehul S.
AU - García-Sastre, Adolfo
AU - Schotsaert, Michael
AU - Suzuki, Tadaki
AU - Boon, Adrianus C.M.
AU - Diamond, Michael S.
AU - Kawaoka, Yoshihiro
N1 - Funding Information: Acknowledgements 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. Funding Information: Competing interests M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. The Boon laboratory has received unrelated funding support in sponsored research agreements from AI Therapeutics, AbbVie Inc., GreenLight Biosciences Inc., and Nano targeting & Therapy Biopharma Inc. M.S.S. serves on Advisory boards for Moderna and Ocugen. Y.K. has received unrelated funding support from Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Inc., Shionogi & Co. Ltd, Otsuka Pharmaceutical, KM Biologics, Kyoritsu Seiyaku, Shinya Corporation and Fuji Rebio. The A.G.-S. laboratory has received unrelated research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma and Merck. A.G.-S. has paid or equity-based consulting agreements for the following companies: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, Paratus, CureLab Oncology, CureLab Veterinary and Pfizer, outside the reported work. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside the reported work. Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays that list Viviana Simon as co-inventor. S.P. has received unrelated research support from BioAge Laboratories and Autonomous Therapeutics Inc. The remaining authors declare no competing interests. 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. Publisher Copyright: © 2022, The Author(s).
PY - 2022/3/24
Y1 - 2022/3/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85123443087&partnerID=8YFLogxK
U2 - 10.1038/s41586-022-04441-6
DO - 10.1038/s41586-022-04441-6
M3 - Article
C2 - 35062015
AN - SCOPUS:85123443087
SN - 0028-0836
VL - 603
SP - 687
EP - 692
JO - Nature
JF - Nature
IS - 7902
ER -