Novel super-neutralizing antibody UT28K is capable of protecting against infection from a wide variety of SARS-CoV-2 variants
Tatsuhiko Ozawa,
Hideki Tani,
Yuki Anraku,
Shunsuke Kita,
Emiko Igarashi,
Yumiko Saga,
Noriko Inasaki,
Hitoshi Kawasuji,
Hiroshi Yamada,
so-Ichiro Sasaki,
Mayu Somekawa,
Jiei Sasaki,
Yoshihiro Hayakawa,
Yoshihiro Yamamoto,
Yoshitomo Morinaga,
Nobuyuki Kurosawa,
Masaharu Isobe,
Hideo Fukuhara,
Katsumi Maenaka,
Takao Hashiguchi,
Hiroyuki Kishi,
Isao Kitajima,
Shigeru Saito,
Hideki Niimi
Affiliations
Tatsuhiko Ozawa
Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
Hideki Tani
Department of Virology, Toyama Institute of Health, Toyama, Japan
Yuki Anraku
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
Shunsuke Kita
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
Emiko Igarashi
Department of Virology, Toyama Institute of Health, Toyama, Japan
Yumiko Saga
Department of Virology, Toyama Institute of Health, Toyama, Japan
Noriko Inasaki
Department of Virology, Toyama Institute of Health, Toyama, Japan
Hitoshi Kawasuji
Department of Clinical Infectious Diseases, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
Hiroshi Yamada
Department of Microbiology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
so-Ichiro Sasaki
Section of Host Defences, Department of Bioscience, Institute of Natural Medicine, University of Toyama, Japan
Mayu Somekawa
Department of Microbiology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
Jiei Sasaki
Laboratory of Medical Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
Yoshihiro Hayakawa
Section of Host Defences, Department of Bioscience, Institute of Natural Medicine, University of Toyama, Japan
Yoshihiro Yamamoto
Department of Clinical Infectious Diseases, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
Yoshitomo Morinaga
Department of Microbiology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
Nobuyuki Kurosawa
Department of Life Sciences and Bioengineering, Laboratory of Molecular and Cellular Biology, Faculty of Engineering, Academic Assembly, University of Toyama, Toyama, Japan
Masaharu Isobe
Department of Life Sciences and Bioengineering, Laboratory of Molecular and Cellular Biology, Faculty of Engineering, Academic Assembly, University of Toyama, Toyama, Japan
Hideo Fukuhara
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
Katsumi Maenaka
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
Takao Hashiguchi
Laboratory of Medical Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
Hiroyuki Kishi
Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
Isao Kitajima
Administrative office, University of Toyama, Toyama, Japan
Shigeru Saito
Administrative office, University of Toyama, Toyama, Japan
Hideki Niimi
Department of Clinical Laboratory and Molecular Pathology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
Many potent neutralizing SARS-CoV-2 antibodies have been developed and used for therapies. However, the effectiveness of many antibodies has been reduced against recently emerging SARS-CoV-2 variants, especially the Omicron variant. We identified a highly potent SARS-CoV-2 neutralizing antibody, UT28K, in COVID-19 convalescent individuals who recovered from a severe condition. UT28K showed efficacy in neutralizing SARS-CoV-2 in an in vitro assay and in vivo prophylactic treatment, and the reactivity to the Omicron strain was reduced. The structural analyses revealed that antibody UT28K Fab and SARS-CoV-2 RBD protein interactions were mainly chain-dominated antigen-antibody interactions. In addition, a mutation analysis suggested that the emergence of a UT28K neutralization-resistant SARS-CoV-2 variant was unlikely, as this variant would likely lose its competitive advantage over circulating SARS-CoV-2. Our data suggest that UT28K offers potent protection against SARS-CoV-2, including newly emerging variants.
