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

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...

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Published inThe Journal of experimental medicine Vol. 218; no. 12
Main Authors Shinnakasu, Ryo, Sakakibara, Shuhei, Yamamoto, Hiromi, Wang, Po-hung, Moriyama, Saya, Sax, Nicolas, Ono, Chikako, Yamanaka, Atsushi, Adachi, Yu, Onodera, Taishi, Sato, Takashi, Shinkai, Masaharu, Suzuki, Ryosuke, Matsuura, Yoshiharu, Hashii, Noritaka, Takahashi, Yoshimasa, Inoue, Takeshi, Yamashita, Kazuo, Kurosaki, Tomohiro
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 06.12.2021
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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.
AbstractList 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.
Shinnakasu et al. show that the glycan engineering immunogens of SARS-CoV-2 spike receptor-binding domain (RBD) elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibodies, thereby manifesting significant neutralizing activity not only for SARS-CoV-2 but also for more broad SARS-related viruses. 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.
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.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.
Author Inoue, Takeshi
Shinkai, Masaharu
Onodera, Taishi
Yamamoto, Hiromi
Wang, Po-hung
Adachi, Yu
Sax, Nicolas
Shinnakasu, Ryo
Yamanaka, Atsushi
Hashii, Noritaka
Ono, Chikako
Moriyama, Saya
Takahashi, Yoshimasa
Yamashita, Kazuo
Suzuki, Ryosuke
Sato, Takashi
Matsuura, Yoshiharu
Sakakibara, Shuhei
Kurosaki, Tomohiro
AuthorAffiliation 12 Laboratory for Lymphocyte Differentiation, Research Center for Allergy and Immunology, RIKEN, Yokohama, Japan
2 Laboratory of Immune Regulation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
10 Department of Virology II, National Institute of Infectious Diseases, Tokyo, 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
13 Center for Infectious Diseases Education and Research, Osaka University, Osaka, Japan
4 KOTAI Biotechnologies, Inc., Osaka, Japan
7 Mahidol-Osaka Center for Infectious Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
3 Reseach Center for Drug and Vaccine Development, National Institute of Infection Diseases, Tokyo, Japan
8 Mahidol-Osaka Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
9 Tok
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R. Shinnakasu and S. Sakakibara contributed equally to this paper.
Disclosures: R. Shinnakasu, S. Sakakibara, and T. Kurosaki reported a patent to "glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses" pending. N. Sax and K. Yamashita reported personal fees from KOTAI Biotechnologies, Inc. outside the submitted work. No other disclosures were reported.
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Snippet Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. The SARS-CoV-2 spike receptor-binding...
Shinnakasu et al. show that the glycan engineering immunogens of SARS-CoV-2 spike receptor-binding domain (RBD) elicited higher proportions of the...
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SubjectTerms 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
Infectious Disease and Host Defense
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
Title Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses
URI https://www.ncbi.nlm.nih.gov/pubmed/34623376
https://www.proquest.com/docview/2580693063
https://pubmed.ncbi.nlm.nih.gov/PMC8641255
Volume 218
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