Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike

Daichi Yamasoba; Izumi Kimura; Hesham Nasser; Yuhei Morioka; Naganori Nao; Jumpei Ito; Keiya Uriu; Masumi Tsuda; Jiri Zahradnik; Kotaro Shirakawa; Rigel Suzuki; Mai Kishimoto; Yusuke Kosugi; Kouji Kobiyama; Teppei Hara; Mako Toyoda; Yuri L Tanaka; Erika P Butlertanaka; Ryo Shimizu; Hayato Ito; Lei Wang; Yoshitaka Oda; Yasuko Orba; Michihito Sasaki; Kayoko Nagata; Kumiko Yoshimatsu; Hiroyuki Asakura; Mami Nagashima; Kenji Sadamasu; Kazuhisa Yoshimura; Jin Kuramochi; Motoaki Seki; Ryoji Fujiki; Atsushi Kaneda; Tadanaga Shimada; Taka-Aki Nakada; Seiichiro Sakao; Takuji Suzuki; Takamasa Ueno; Akifumi Takaori-Kondo; Ken J Ishii; Gideon Schreiber; Genotype to Phenotype Japan (G2P-Japan) Consortium; Hirofumi Sawa; Akatsuki Saito; Takashi Irie; Shinya Tanaka; Keita Matsuno; Takasuke Fukuhara; Terumasa Ikeda; Kei Sato

doi:10.1016/j.cell.2022.04.035

Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike

Cell. 2022 Jun 9;185(12):2103-2115.e19. doi: 10.1016/j.cell.2022.04.035. Epub 2022 May 2.

Authors

Daichi Yamasoba¹, Izumi Kimura², Hesham Nasser³, Yuhei Morioka⁴, Naganori Nao⁵, Jumpei Ito², Keiya Uriu⁶, Masumi Tsuda⁷, Jiri Zahradnik⁸, Kotaro Shirakawa⁹, Rigel Suzuki⁴, Mai Kishimoto¹⁰, Yusuke Kosugi¹¹, Kouji Kobiyama¹², Teppei Hara¹³, Mako Toyoda¹⁴, Yuri L Tanaka¹⁵, Erika P Butlertanaka¹⁵, Ryo Shimizu¹⁶, Hayato Ito⁴, Lei Wang⁷, Yoshitaka Oda¹⁷, Yasuko Orba¹⁸, Michihito Sasaki¹⁹, Kayoko Nagata⁹, Kumiko Yoshimatsu²⁰, Hiroyuki Asakura²¹, Mami Nagashima²¹, Kenji Sadamasu²¹, Kazuhisa Yoshimura²¹, Jin Kuramochi²², Motoaki Seki²³, Ryoji Fujiki²³, Atsushi Kaneda²³, Tadanaga Shimada²⁴, Taka-Aki Nakada²⁴, Seiichiro Sakao²⁵, Takuji Suzuki²⁵, Takamasa Ueno¹⁴, Akifumi Takaori-Kondo⁹, Ken J Ishii¹², Gideon Schreiber⁸; Genotype to Phenotype Japan (G2P-Japan) Consortium; Hirofumi Sawa²⁶, Akatsuki Saito²⁷, Takashi Irie²⁸, Shinya Tanaka²⁹, Keita Matsuno³⁰, Takasuke Fukuhara³¹, Terumasa Ikeda³², Kei Sato³³

Affiliations

¹ Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Faculty of Medicine, Kobe University, Kobe, Japan.
² Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
³ Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan; Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
⁴ Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
⁵ Division of International Research Promotion, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; One Health Research Center, Hokkaido University, Sapporo, Japan.
⁶ Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁷ Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan; Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan.
⁸ Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
⁹ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹⁰ Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
¹¹ Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan; Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
¹² Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹³ Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁴ Division of Infection and immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan.
¹⁵ Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.
¹⁶ Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan.
¹⁷ Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
¹⁸ Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.
¹⁹ Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
²⁰ Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
²¹ Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.
²² Interpark Kuramochi Clinic, Utsunomiya, Japan.
²³ Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
²⁴ Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
²⁵ Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
²⁶ Division of International Research Promotion, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; One Health Research Center, Hokkaido University, Sapporo, Japan; Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
²⁷ Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan; Center for Animal Disease Control, University of Miyazaki, Chiba, Japan; Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki, Japan. Electronic address: sakatsuki@cc.miyazaki-u.ac.jp.
²⁸ Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: tirie@hiroshima-u.ac.jp.
²⁹ Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan; Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan. Electronic address: tanaka@med.hokudai.ac.jp.
³⁰ One Health Research Center, Hokkaido University, Sapporo, Japan; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; Division of Risk Analysis and Management, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan. Electronic address: matsuk@czc.hokudai.ac.jp.
³¹ Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: fukut@pop.med.hokudai.ac.jp.
³² Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan. Electronic address: ikedat@kumamoto-u.ac.jp.
³³ Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency, Kawaguchi, Japan. Electronic address: keisato@g.ecc.u-tokyo.ac.jp.

Abstract

Soon after the emergence and global spread of the SARS-CoV-2 Omicron lineage BA.1, another Omicron lineage, BA.2, began outcompeting BA.1. The results of statistical analysis showed that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralization experiments revealed that immunity induced by COVID vaccines widely administered to human populations is not effective against BA.2, similar to BA.1, and that the antigenicity of BA.2 is notably different from that of BA.1. Cell culture experiments showed that the BA.2 spike confers higher replication efficacy in human nasal epithelial cells and is more efficient in mediating syncytia formation than the BA.1 spike. Furthermore, infection experiments using hamsters indicated that the BA.2 spike-bearing virus is more pathogenic than the BA.1 spike-bearing virus. Altogether, the results of our multiscale investigations suggest that the risk of BA.2 to global health is potentially higher than that of BA.1.

Keywords: B.1.1.529; BA.1; BA.2; COVID-19; Omicron; SARS-CoV-2; fusogenicity; pathogenicity; transmissibility.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
COVID-19* / virology
Cricetinae
Epithelial Cells
Humans
SARS-CoV-2* / genetics
SARS-CoV-2* / pathogenicity
Spike Glycoprotein, Coronavirus* / genetics

Substances

Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2