| Autor: |
Kawaoka Y; University of Wisconsin-Madison., Uraki R; National Center for Global Health and Medicine Research Institute., Kiso M; Institute of Medical Sciences, University of Tokyo., Iida S; National Institute of Infectious Diseases., Imai M; University of Tokyo., Takashita E; National Institute of Infectious Diseases., Kuroda M; University of Wisconsin at Madison., Halfmann P; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA., Loeber S; University of Wisconsin-Madison., Maemura T; University of Wisconsin., Yamayoshi S; University Of Tokyo., Fujisaki S; National Institute of Infectious Diseases., Wang Z; Utah State University., Ito M; University of Tokyo, Institute of Medical Science., Ujie M; Division of Virology, Institute of Medical Science, University of Tokyo., Iwatsuki-Horimoto K; University of Tokyo., Furusawa Y; Division of Virology, Institute of Medical Science, University of Tokyo., Wright R; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison., Chong Z; Washington University., Ozono S; National Institute of Infectious Diseases., Yasuhara A; Division of Virology, Institute of Medical Science, University of Tokyo., Ueki H; The University of Tokyo., Sakai Y; Institute of Medical Sciences, University of Tokyo., Li R; Department of Animal Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University., Liu Y; Department of Animal Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University., Larson D; Utah State University, College of Agriculture and Applied Sciences., Koga M; The Institute of Medical Science, the University of Tokyo., Tsutsumi T; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo., Adachi E; The Institute of Medical Science, the University of Tokyo., Saito M; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo., Yamamoto S; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo., Matsubara S; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo., Hagihara M; Division of Infection Control, Eiju General Hospital., Mitamura K; Division of Infection Control, Eiju General Hospital., Sato T; Disease Control and Prevention Center, National Center for Global Health and Medicine Hospital., Hojo M; Department of Respiratory Medicine, National Center for Global Health and Medicine Hospital., Hattori SI; National Center for Global Health and Medicine Research Institute., Maeda K; National Center For Global Health and Medicine., Okuda M; Department of Virology, Institute of Medical Science, University of Tokyo., Murakami J; Department of Virology, Institute of Medical Science, University of Tokyo., Duong C; Department of Virology, Institute of Medical Science, University of Tokyo., Godbole S; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health., Douek D; NIH., Watanabe S; National Institute of Infectious Diseases., Ohmagari N; Disease Control and Prevention Center, National Center for Global Health and Medicine., Yotsuyanagi H; University of Tokyo., Diamond M; Washington University in Saint Louis., Hasegawa H; National Institute of Infectious Diseases., Mitsuya H; National Center for Global Health and Medicine Research Institute., Suzuki T; National Institute of Infectious Diseases. |
| Abstrakt: |
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. |
