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A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site.
Onodera, Taishi; Kita, Shunsuke; Adachi, Yu; Moriyama, Saya; Sato, Akihiko; Nomura, Takao; Sakakibara, Shuhei; Inoue, Takeshi; Tadokoro, Takashi; Anraku, Yuki; Yumoto, Kohei; Tian, Cong; Fukuhara, Hideo; Sasaki, Michihito; Orba, Yasuko; Shiwa, Nozomi; Iwata, Naoko; Nagata, Noriyo; Suzuki, Tateki; Sasaki, Jiei; Sekizuka, Tsuyoshi; Tonouchi, Keisuke; Sun, Lin; Fukushi, Shuetsu; Satofuka, Hiroyuki; Kazuki, Yasuhiro; Oshimura, Mitsuo; Kurosaki, Tomohiro; Kuroda, Makoto; Matsuura, Yoshiharu; Suzuki, Tadaki; Sawa, Hirofumi; Hashiguchi, Takao; Maenaka, Katsumi; Takahashi, Yoshimasa.
  • Onodera T; Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Kita S; Laboratory of Biomolecular Science, and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
  • Adachi Y; Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Moriyama S; Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Sato A; Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan; Drug Discovery & Disease Research Laboratory, Shionogi & Co., Ltd., Osaka 561-0825, Japan.
  • Nomura T; Laboratory of Biomolecular Science, and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
  • Sakakibara S; Laboratory of Immune Regulation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
  • Inoue T; Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
  • Tadokoro T; Laboratory of Biomolecular Science, and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
  • Anraku Y; Laboratory of Biomolecular Science, and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
  • Yumoto K; Laboratory of Biomolecular Science, and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
  • Tian C; Laboratory of Biomolecular Science, and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
  • Fukuhara H; Laboratory of Biomolecular Science, and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan; Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Sapporo 060-0812, Japan.
  • Sasaki M; Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
  • Orba Y; Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
  • Shiwa N; Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • Iwata N; Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • Nagata N; Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • Suzuki T; Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
  • Sasaki J; Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
  • Sekizuka T; Pathogen Genomic Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Tonouchi K; Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan.
  • Sun L; Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Fukushi S; Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Satofuka H; Chromosome Engineering Research Center, Tottori University, Tottori 683-8503, Japan.
  • Kazuki Y; Chromosome Engineering Research Center, Tottori University, Tottori 683-8503, Japan; Division of Genome and Cellular Functions, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Tottori 683-8503, Japan.
  • Oshimura M; Trans Chromosomics Inc., Tottori 683-8503, Japan.
  • Kurosaki T; Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
  • Kuroda M; Pathogen Genomic Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Matsuura Y; Laboratory of Virus Control, Center for Infectious Diseases Education and Research, Osaka University, Osaka 565-0871, Japan.
  • Suzuki T; Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • Sawa H; Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
  • Hashiguchi T; Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan; Laboratory of Medical Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
  • Maenaka K; Laboratory of Biomolecular Science, and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan; Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Sapporo 060-0812, Japan. Electronic address: maenaka@
  • Takahashi Y; Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan. Electronic address: ytakahas@niid.go.jp.
Immunity ; 54(10): 2385-2398.e10, 2021 10 12.
Article in English | MEDLINE | ID: covidwho-1370548
ABSTRACT
Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but the variability of RBS epitopes hampers broad neutralization of multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an RBS antibody with a germline VH gene that potently neutralized SARS-related coronaviruses, including SARS-CoV and SARS-CoV-2 variants. X-ray crystallography revealed coordinated recognition by the heavy chain of non-RBS conserved sites and the light chain of RBS with a binding angle mimicking the angiotensin-converting enzyme 2 (ACE2) receptor. The minimum footprints in the hypervariable region of RBS contributed to the breadth of neutralization, which was enhanced by immunoglobulin G3 (IgG3) class switching. The coordinated binding resulted in broad neutralization of SARS-CoV and emerging SARS-CoV-2 variants of concern. Low-dose therapeutic antibody treatment in hamsters reduced the virus titers and morbidity during SARS-CoV-2 challenge. The structural basis for broad neutralizing activity may inform the design of a broad spectrum of therapeutics and vaccines.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cross Reactions / Broadly Neutralizing Antibodies / SARS-CoV-2 Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.08.025

Full text: Available Collection: International databases Database: MEDLINE Main subject: Cross Reactions / Broadly Neutralizing Antibodies / SARS-CoV-2 Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.08.025