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

doi:10.1080/19420862.2022.2072455

Novel super-neutralizing antibody UT28K is capable of protecting against infection from a wide variety of SARS-CoV-2 variants

MAbs. 2022 Jan-Dec;14(1):2072455. doi: 10.1080/19420862.2022.2072455.

Authors

Tatsuhiko Ozawa¹, Hideki Tani², Yuki Anraku³, Shunsuke Kita³, Emiko Igarashi², Yumiko Saga², Noriko Inasaki², Hitoshi Kawasuji⁴, Hiroshi Yamada⁵, So-Ichiro Sasaki⁶, Mayu Somekawa⁵, Jiei Sasaki⁷, Yoshihiro Hayakawa⁶, Yoshihiro Yamamoto⁴, Yoshitomo Morinaga⁵, Nobuyuki Kurosawa⁸, Masaharu Isobe⁸, Hideo Fukuhara³, Katsumi Maenaka³, Takao Hashiguchi⁷, Hiroyuki Kishi¹, Isao Kitajima⁹, Shigeru Saito⁹, Hideki Niimi¹⁰

Affiliations

¹ Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.
² Department of Virology, Toyama Institute of Health, Toyama, Japan.
³ Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
⁴ Department of Clinical Infectious Diseases, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.
⁵ Department of Microbiology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.
⁶ Section of Host Defences, Department of Bioscience, Institute of Natural Medicine, University of Toyama, Japan.
⁷ Laboratory of Medical Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
⁸ Department of Life Sciences and Bioengineering, Laboratory of Molecular and Cellular Biology, Faculty of Engineering, Academic Assembly, University of Toyama, Toyama, Japan.
⁹ Administrative office, University of Toyama, Toyama, Japan.
¹⁰ Department of Clinical Laboratory and Molecular Pathology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; monoclonal antibody; neutralizing antibody; super-neutralizing antibody.

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
COVID-19* / prevention & control
Humans
SARS-CoV-2*

Substances

Antibodies, Neutralizing
Antibodies, Viral

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

This work was supported by Discretionary Fund of the President of the University of Toyama (H.N.), Grant for the Promotion of National University Reform from the Ministry of Education, Culture, Sports, Science and Technology (H.N.), Grant from the Toyama Pharmaceutical Valley Development Consortium (H.N.), the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under grant number JP21am0101077 (T.O.), and JP21am0101093 (K.M.), Ministry of Education, Culture, Sports, Science and Technology grant 20H05773 (T.H.) and JST CREST Grant Number JPMJCR20H8 (T.H.), the Takeda Foundation (K.M.) and Joint Usage/Research Center program of Institute for Frontier Life and Medical Sciences, Kyoto University (K.M.).