Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses

Ryo Shinnakasu; Shuhei Sakakibara; Hiromi Yamamoto; Po-Hung Wang; Saya Moriyama; Nicolas Sax; Chikako Ono; Atsushi Yamanaka; Yu Adachi; Taishi Onodera; Takashi Sato; Masaharu Shinkai; Ryosuke Suzuki; Yoshiharu Matsuura; Noritaka Hashii; Yoshimasa Takahashi; Takeshi Inoue; Kazuo Yamashita; Tomohiro Kurosaki

doi:10.1084/jem.20211003

Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses

J Exp Med. 2021 Dec 6;218(12):e20211003. doi: 10.1084/jem.20211003. Epub 2021 Oct 8.

Authors

Ryo Shinnakasu^#¹, Shuhei Sakakibara^#², Hiromi Yamamoto¹, Po-Hung Wang¹, Saya Moriyama³, Nicolas Sax⁴, Chikako Ono^{5

6}, Atsushi Yamanaka^{7

8}, Yu Adachi³, Taishi Onodera³, Takashi Sato⁹, Masaharu Shinkai⁹, Ryosuke Suzuki¹⁰, Yoshiharu Matsuura^{5

6}, Noritaka Hashii¹¹, Yoshimasa Takahashi³, Takeshi Inoue¹, Kazuo Yamashita⁴, Tomohiro Kurosaki^{1

12

13}

Affiliations

¹ Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
² Laboratory of Immune Regulation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
³ Reseach Center for Drug and Vaccine Development, National Institute of Infection Diseases, Tokyo, Japan.
⁴ KOTAI Biotechnologies, Inc., Osaka, Japan.
⁵ Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
⁶ Laboratory of Virus Control, Center for Infectious Diseases Education and Research, Osaka University, Osaka, Japan.
⁷ Mahidol-Osaka Center for Infectious Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
⁸ Mahidol-Osaka Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
⁹ Tokyo Shinagawa Hospital, Tokyo, Japan.
¹⁰ Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
¹¹ Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Kawasaki, Japan.
¹² Laboratory for Lymphocyte Differentiation, Research Center for Allergy and Immunology, RIKEN, Yokohama, Japan.
¹³ Center for Infectious Diseases Education and Research, Osaka University, Osaka, Japan.

^# Contributed equally.

Abstract

Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. These results have implications for the design of SARS-like virus vaccines.

Publication types

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

MeSH terms

Amino Acid Motifs
Animals
Antibodies, Viral / immunology*
Broadly Neutralizing Antibodies / immunology*
COVID-19 / genetics
COVID-19 / immunology*
COVID-19 / prevention & control
COVID-19 Vaccines / genetics
COVID-19 Vaccines / immunology
Female
Humans
Male
Mice
Mice, Inbred BALB C
Polysaccharides / genetics
Polysaccharides / immunology*
Protein Domains
SARS-CoV-2 / genetics
SARS-CoV-2 / immunology*
Severe acute respiratory syndrome-related coronavirus / genetics
Severe acute respiratory syndrome-related coronavirus / immunology*
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology*

Substances

Antibodies, Viral
Broadly Neutralizing Antibodies
COVID-19 Vaccines
Polysaccharides
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Abstract

Publication types

MeSH terms

Substances

Grants and funding