Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5

Izumi Kimura(The University of Tokyo), Daichi Yamasoba(Kobe University), Tomokazu Tamura(Hokkaido University), Naganori Nao(Sapporo University), Tateki Suzuki(Kyoto University), Yoshitaka Oda(Hokkaido University), Shuya Mitoma(University of Miyazaki), Jumpei Ito(The University of Tokyo), Hesham Nasser(Suez Canal University), Jiří Zahradník(Weizmann Institute of Science), Keiya Uriu(Tokyo Medical University), Shigeru Fujita(Tokyo Medical University), Yusuke Kosugi(Tokyo Medical University), Lei Wang(Hokkaido University), Masumi Tsuda(Hokkaido University), Mai Kishimoto(Hokkaido University), Hayato Ito(Hokkaido University), Rigel Suzuki(Hokkaido University), Ryo Shimizu(Kumamoto University), MST Monira Begum(Kumamoto University), Kumiko Yoshimatsu(Hokkaido University), Kanako Kimura(Kyoto University), Jiei Sasaki(Kyoto University), Kaori Sasaki‐Tabata(Kyushu University), Yuki Yamamoto, Tetsuharu Nagamoto, Jun Kanamune, Kouji Kobiyama(International Vaccine Institute), Hiroyuki Asakura(Tokyo Metropolitan Institute of Public Health), Mami Nagashima(Tokyo Metropolitan Institute of Public Health), Kenji Sadamasu(Tokyo Metropolitan Institute of Public Health), Kazuhisa Yoshimura(Tokyo Metropolitan Institute of Public Health), Kotaro Shirakawa(Kyoto University), Akifumi Takaori‐Kondo(Kyoto University), Jin Kuramochi(Tokyo Medical and Dental University), Gideon Schreiber(Weizmann Institute of Science), Ken J. Ishii(International Vaccine Institute), Takao Hashiguchi(Kyoto University), Terumasa Ikeda(Kumamoto University), Akatsuki Saito(University of Miyazaki), Takasuke Fukuhara(Hokkaido University), Shinya Tanaka(Hokkaido University), Keita Matsuno(Sapporo University), Kei Sato(National Institute of Infectious Diseases)
Cell
September 14, 2022
10.1016/j.cell.2022.09.018
Cited by 295Open Access
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Abstract

After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.

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