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

Author

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

Published
2022
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5. Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2

Author

Uraki, Ryuta, Kiso, Maki, Iida, Shun, Imai, Masaki, Takashita, Emi, Kuroda, Makoto, Halfmann, Peter J., Loeber, Samantha, Maemura, Tadashi, Yamayoshi, Seiya, Fujisaki, Seiichiro, Wang, Zhongde, Ito, Mutsumi, Ujie, Michiko, Iwatsuki-Horimoto, Kiyoko, Furusawa, Yuri, Wright, Ryan, Chong, Zhenlu, Ozono, Seiya, Yasuhara, Atsuhiro, Ueki, Hiroshi, Sakai-Tagawa, Yuko, Li, Rong, Liu, Yanan, Larson, Deanna, Koga, Michiko, Tsutsumi, Takeya, Adachi, Eisuke, Saito, Makoto, Yamamoto, Shinya, Hagihara, Masao, Mitamura, Keiko, Sato, Tetsuro, Hojo, Masayuki, Hattori, Shin-ichiro, Maeda, Kenji, Valdez, Riccardo, Okuda, Moe, Murakami, Jurika, Duong, Calvin, Godbole, Sucheta, Douek, Daniel C., Maeda, Ken, Watanabe, Shinji, Gordon, Aubree, Ohmagari, Norio, Yotsuyanagi, Hiroshi, Diamond, Michael S., Hasegawa, Hideki, Mitsuya, Hiroaki, Suzuki, Tadaki, and Kawaoka, Yoshihiro

Published
2022
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6. Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains

Author

Case, James Brett, Mackin, Samantha, Errico, John M., Chong, Zhenlu, Madden, Emily A., Whitener, Bradley, Guarino, Barbara, Schmid, Michael A., Rosenthal, Kim, Ren, Kuishu, Dang, Ha V., Snell, Gyorgy, Jung, Ana, Droit, Lindsay, Handley, Scott A., Halfmann, Peter J., Kawaoka, Yoshihiro, Crowe, Jr., James E., Fremont, Daved H., Virgin, Herbert W., Loo, Yueh-Ming, Esser, Mark T., Purcell, Lisa A., Corti, Davide, and Diamond, Michael S.

Published
2022
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8. An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo

Author

Tsuji, Moriya, primary, Nair, Manoj S., additional, Masuda, Kazuya, additional, Castagna, Candace, additional, Chong, Zhenlu, additional, Darling, Tamarand L., additional, Seehra, Kuljeet, additional, Hwang, Youngmin, additional, Ribeiro, Ágata Lopes, additional, Ferreira, Geovane Marques, additional, Corredor, Laura, additional, Coelho-dos-Reis, Jordana Grazziela Alves, additional, Tsuji, Yukiko, additional, Mori, Munemasa, additional, Boon, Adrianus C. M., additional, Diamond, Michael S., additional, Huang, Yaoxing, additional, and Ho, David D., additional

Published
2023
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9. An Immunostimulatory Glycolipid That Blocks SARS-CoV-2, RSV, and Influenza Infections In Vivo

Author

Ho, David, primary, Tsuji, Moriya, additional, Nair, Manoj, additional, Masuda, Kazuya, additional, Castagna, Candace, additional, Chong, Zhenlu, additional, Darling, Tamarand, additional, Seehra, Kuljeet, additional, Ribeiro, Ágata, additional, Ferreira, Geovane, additional, Corredor, Laura, additional, Coelho-dos-Reis, Jordana Alves, additional, Tsuji, Yukiko, additional, Boon, Adrianus, additional, Diamond, Michael, additional, Huang, Yaoxing, additional, Hwang, Youngmin, additional, and Mori, Munemasa, additional

Published
2023
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10. Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2

Author

Uraki, Ryuta, Kiso, Maki, Iida, Shun, Imai, Masaki, Takashita, Emi, Kuroda, Makoto, Halfmann, Peter J., Loeber, Samantha, Maemura, Tadashi, Yamayoshi, Seiya, Fujisaki, Seiichiro, Wang, Zhongde, Ito, Mutsumi, Ujie, Michiko, Iwatsuki-Horimoto, Kiyoko, Furusawa, Yuri, Wright, Ryan, Chong, Zhenlu, Ozono, Seiya, Yasuhara, Atsuhiro, Ueki, Hiroshi, Sakai-Tagawa, Yuko, Li, Rong, Liu, Yanan, Larson, Deanna, Koga, Michiko, Tsutsumi, Takeya, Adachi, Eisuke, Saito, Makoto, Yamamoto, Shinya, Hagihara, Masao, Mitamura, Keiko, Sato, Tetsuro, Hojo, Masayuki, Hattori, Shin-ichiro, Maeda, Kenji, Valdez, Riccardo, Okuda, Moe, Murakami, Jurika, Duong, Calvin, Godbole, Sucheta, Douek, Daniel C., Maeda, Ken, Watanabe, Shinji, Gordon, Aubree, Ohmagari, Norio, Yotsuyanagi, Hiroshi, Diamond, Michael S., Hasegawa, Hideki, Mitsuya, Hiroaki, Suzuki, Tadaki, and Kawaoka, Yoshihiro

Abstract

The recent emergence of SARS-CoV-2 Omicron (B.1.1.529 lineage) variants possessing numerous mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies and antiviral drugs for COVID-19 against these variants1,2. The original Omicron lineage, BA.1, prevailed in many countries, but more recently, BA.2 has become dominant in at least 68 countries3. Here we evaluated the replicative ability and pathogenicity of authentic infectious BA.2 isolates in immunocompetent and human ACE2-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone4, we observed similar infectivity and pathogenicity in mice and hamsters for BA.2 and BA.1, and less pathogenicity compared with early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from individuals who had recovered from COVID-19 and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987 plus REGN10933, COV2-2196 plus COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir and S-217622) can restrict viral infection in the respiratory organs of BA.2-infected hamsters. These findings suggest that the replication and pathogenicity of BA.2 is similar to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron BA.2 variants.

Published
2024
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13. An Immunostimulatory Glycolipid That Blocks SARS-CoV-2, RSV, and Influenza Infections In Vivo

Author

Ho, David, primary, Tsuji, Moriya, additional, Nair, Manoj, additional, Masuda, Kazuya, additional, Castagna, Candace, additional, Chong, Zhenlu, additional, Darling, Tamarand, additional, Seehra, Kuljeet, additional, Ribeiro, Ágata, additional, Ferreira, Geovane, additional, Corredor, Laura, additional, Coelho-dos-Reis, Jordana Alves, additional, Tsuji, Yukiko, additional, Boon, Adrianus, additional, Diamond, Michael, additional, and Huang, Yaoxing, additional

Published
2022
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15. Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice

Author

Ying, Baoling, primary, Scheaffer, Suzanne M., additional, Whitener, Bradley, additional, Liang, Chieh-Yu, additional, Dmytrenko, Oleksandr, additional, Mackin, Samantha, additional, Wu, Kai, additional, Lee, Diana, additional, Avena, Laura E., additional, Chong, Zhenlu, additional, Case, James Brett, additional, Ma, LingZhi, additional, Kim, Thu T.M., additional, Sein, Caralyn E., additional, Woods, Angela, additional, Berrueta, Daniela Montes, additional, Chang, Gwo-Yu, additional, Stewart-Jones, Guillaume, additional, Renzi, Isabella, additional, Lai, Yen-Ting, additional, Malinowski, Agata, additional, Carfi, Andrea, additional, Elbashir, Sayda M., additional, Edwards, Darin K., additional, Thackray, Larissa B., additional, and Diamond, Michael S., additional

Published
2022
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16. Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains

Author

Case, James Brett, primary, Mackin, Samantha, additional, Errico, John, additional, Chong, Zhenlu, additional, Madden, Emily A., additional, Guarino, Barbara, additional, Schmid, Michael A., additional, Rosenthal, Kim, additional, Ren, Kuishu, additional, Jung, Ana, additional, Droit, Lindsay, additional, Handley, Scott A., additional, Halfmann, Peter J., additional, Kawaoka, Yoshihiro, additional, Crowe, James E., additional, Fremont, Daved H., additional, Virgin, Herbert W., additional, Loo, Yueh-Ming, additional, Esser, Mark T., additional, Purcell, Lisa A., additional, Corti, Davide, additional, and Diamond, Michael S., additional

Published
2022
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17. Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2

Author

Kawaoka, Yoshihiro, primary, Uraki, Ryuta, additional, Kiso, Maki, additional, Iida, Shun, additional, Imai, Masaki, additional, Takashita, Emi, additional, Kuroda, Makoto, additional, Halfmann, Peter, additional, Loeber, Samantha, additional, Maemura, Tadashi, additional, Yamayoshi, Seiya, additional, Fujisaki, Seiichiro, additional, Wang, Zhongde, additional, Ito, Mutsumi, additional, Ujie, Michiko, additional, Iwatsuki-Horimoto, Kiyoko, additional, Furusawa, Yuri, additional, Wright, Ryan, additional, Chong, Zhenlu, additional, Ozono, Seiya, additional, Yasuhara, Atsuhiro, additional, Ueki, Hiroshi, additional, Sakai, Yuko, additional, Li, Rong, additional, Liu, Yanan, additional, Larson, Deanna, additional, Koga, Michiko, additional, Tsutsumi, Takeya, additional, Adachi, Eisuke, additional, Saito, Makoto, additional, Yamamoto, Shinya, additional, Matsubara, Shohei, additional, Hagihara, Masao, additional, Mitamura, Keiko, additional, Sato, Tetsuro, additional, Hojo, Masayuki, additional, Hattori, Shin-ichiro, additional, Maeda, Kenji, additional, Okuda, Moe, additional, Murakami, Jurika, additional, Duong, Calvin, additional, Godbole, Sucheta, additional, Douek, Daniel, additional, Watanabe, Shinji, additional, Ohmagari, Norio, additional, Yotsuyanagi, Hiroshi, additional, Diamond, Michael, additional, Hasegawa, Hideki, additional, Mitsuya, Hiroaki, additional, and Suzuki, Tadaki, additional

Published
2022
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18. Boosting with Omicron-matched or historical mRNA vaccines increases neutralizing antibody responses and protection against B.1.1.529 infection in mice

Author

Ying, Baoling, primary, Scheaffer, Suzanne M., additional, Whitener, Bradley, additional, Liang, Chieh-Yu, additional, Dmytrenko, Oleksandr, additional, Mackin, Samantha, additional, Wu, Kai, additional, Lee, Diana, additional, Avena, Laura E., additional, Chong, Zhenlu, additional, Case, James Brett, additional, Ma, LingZhi, additional, Kim, Thu, additional, Sein, Caralyn, additional, Woods, Angela, additional, Berrueta, Daniela Montes, additional, Carfi, Andrea, additional, Elbashir, Sayda M., additional, Edwards, Darin K., additional, Thackray, Larissa B., additional, and Diamond, Michael S., additional

Published
2022
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20. The SARS-CoV-2 B.1.1.529 Omicron virus causes attenuated infection and disease in mice and hamsters

Author

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

Published
2021
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21. Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection

Author

Winkler, Emma S., primary, Gilchuk, Pavlo, additional, Yu, Jinsheng, additional, Bailey, Adam L., additional, Chen, Rita E., additional, Chong, Zhenlu, additional, Zost, Seth J., additional, Jang, Hyesun, additional, Huang, Ying, additional, Allen, James D., additional, Case, James Brett, additional, Sutton, Rachel E., additional, Carnahan, Robert H., additional, Darling, Tamarand L., additional, Boon, Adrianus C.M., additional, Mack, Matthias, additional, Head, Richard D., additional, Ross, Ted M., additional, Crowe, James E., additional, and Diamond, Michael S., additional

Published
2021
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23. E3 ligase FBXW7 is critical for RIG-I stabilization during antiviral responses

Author

Song, Yinjing, primary, Lai, Lihua, additional, Chong, Zhenlu, additional, He, Jia, additional, Zhang, Yuanyuan, additional, Xue, Yue, additional, Xie, Yiwei, additional, Chen, Songchang, additional, Dong, Ping, additional, Chen, Luoquan, additional, Chen, Zhimin, additional, Dai, Feng, additional, Wan, Xiaopeng, additional, Xiao, Peng, additional, Cao, Xuetao, additional, Liu, Yang, additional, and Wang, Qingqing, additional

Published
2017
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26. Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2.

Author

Kawaoka Y, Uraki R, Kiso M, Iida S, Imai M, Takashita E, Kuroda M, Halfmann P, Loeber S, Maemura T, Yamayoshi S, Fujisaki S, Wang Z, Ito M, Ujie M, Iwatsuki-Horimoto K, Furusawa Y, Wright R, Chong Z, Ozono S, Yasuhara A, Ueki H, Sakai Y, Li R, Liu Y, Larson D, Koga M, Tsutsumi T, Adachi E, Saito M, Yamamoto S, Matsubara S, Hagihara M, Mitamura K, Sato T, Hojo M, Hattori SI, Maeda K, Okuda M, Murakami J, Duong C, Godbole S, Douek D, Watanabe S, Ohmagari N, Yotsuyanagi H, Diamond M, Hasegawa H, Mitsuya H, and Suzuki T

Abstract

The recent emergence of SARS-CoV-2 Omicron variants possessing large numbers of mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies, and antiviral drugs for COVID-19 against these variants1,2. While the original Omicron lineage, BA.1, has become dominant in many countries, BA.2 has been detected in at least 67 countries and has become dominant in the Philippines, India, and Denmark. Here, we evaluated the replicative ability and pathogenicity of an authentic infectious BA.2 isolate in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone3, we observed similar infectivity and pathogenicity in mice and hamsters between BA.2 and BA.1, and less pathogenicity compared to early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from COVID-19 convalescent individuals and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987/REGN10933, COV2-2196/COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir, and S-217622) can restrict viral infection in the respiratory organs of hamsters infected with BA.2. These findings suggest that the replication and pathogenicity of BA.2 is comparable to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron/BA.2 variants.

Published
2022
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27. Boosting with Omicron-matched or historical mRNA vaccines increases neutralizing antibody responses and protection against B.1.1.529 infection in mice.

Author

Ying B, Scheaffer SM, Whitener B, Liang CY, Dmytrenko O, Mackin S, Wu K, Lee D, Avena LE, Chong Z, Case JB, Ma L, Kim T, Sein C, Woods A, Berrueta DM, Carfi A, Elbashir SM, Edwards DK, Thackray LB, and Diamond MS

Abstract

The B.1.1.529 Omicron variant jeopardizes vaccines designed with early pandemic spike antigens. Here, we evaluated in mice the protective activity of the Moderna mRNA-1273 vaccine against B.1.1.529 before or after boosting with preclinical mRNA-1273 or mRNA-1273.529, an Omicron-matched vaccine. Whereas two doses of mRNA-1273 vaccine induced high levels of serum neutralizing antibodies against historical WA1/2020 strains, levels were lower against B.1.1.529 and associated with infection and inflammation in the lung. A primary vaccination series with mRNA-1273.529 potently neutralized B.1.1.529 but showed limited inhibition of historical or other SARS-CoV-2 variants. However, boosting with mRNA-1273 or mRNA-1273.529 vaccines increased serum neutralizing titers and protection against B.1.1.529 infection. Nonetheless, the levels of inhibitory antibodies were higher, and viral burden and cytokines in the lung were slightly lower in mice given the Omicron-matched mRNA booster. Thus, in mice, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against B.1.1.529 infection with limited differences in efficacy measured.

Published
2022
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28. Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron.

Author

Chong Z, Karl CE, Halfmann PJ, Kawaoka Y, Winkler ES, Yu J, and Diamond MS

Abstract

Although vaccines and monoclonal antibody countermeasures have reduced the morbidity and mortality associated with SARS-CoV-2 infection, variants with constellations of mutations in the spike gene threaten their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolution are needed. The host-derived cytokine IFN-λ has been proposed as a possible treatment based on correlative studies in human COVID-19 patients. Here, we show IFN-λ protects against SARS-CoV-2 B.1.351 (Beta) and B.1.1.529 (Omicron)variants in three strains of conventional and human ACE2 transgenic mice. Prophylaxis or therapy with nasally-delivered IFN-λ2 limited infection of historical or variant (B.1.351 and B.1.1.529) SARS-CoV-2 strains in the upper and lower respiratory tracts without causing excessive inflammation. In the lung, IFN-λ was produced preferentially in epithelial cells and acted on radio-resistant cells to protect against of SARS-CoV-2 infection. Thus, inhaled IFN-λ may have promise as a treatment for evolving SARS-CoV-2 variants that develop resistance to antibody-based countermeasures.

Published
2022
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29. The SARS-CoV-2 B.1.1.529 Omicron virus causes attenuated infection and disease in mice and hamsters.

Author

Diamond M, Halfmann P, Maemura T, Iwatsuki-Horimoto K, Iida S, Kiso M, Scheaffer S, Darling T, Joshi A, Loeber S, Foster S, Ying B, Whitener B, Floyd K, Ujie M, Nakajima N, Ito M, Wright R, Uraki R, Li R, Sakai Y, Liu Y, Larson D, Osorio J, Hernandez-Ortiz J, Čiuoderis K, Florek K, Patel M, Bateman A, Odle A, Wong LY, Wang Z, Edara VV, Chong Z, Thackray L, Ueki H, Yamayoshi S, Imai M, Perlman S, Webby R, Seder R, Suthar M, Garcia-Sastre A, Schotsaert M, Suzuki T, Boon A, Kawaoka Y, Douek D, Moliva J, Sullivan N, Gagne M, Ransier A, Case J, Jeevan T, Franks J, Fabrizio T, DeBeauchamp J, Kercher L, Seiler P, Singh G, Warang P, Gonzalez-Reiche AS, Sordillo E, van Bakel H, and Simon V

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.

Published
2021
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