tetano
Editor, Senior Moderator
J Exp Med
. 2021 Dec 6;218(12):e20211003.
doi: 10.1084/jem.20211003. Epub 2021 Oct 8.
Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses
Ryo Shinnakasu[SUP] #[/SUP][SUP] 1 [/SUP], Shuhei Sakakibara[SUP] #[/SUP][SUP] 2 [/SUP], Hiromi Yamamoto[SUP] 1 [/SUP], Po-Hung Wang[SUP] 1 [/SUP], Saya Moriyama[SUP] 3 [/SUP], Nicolas Sax[SUP] 4 [/SUP], Chikako Ono[SUP] 5 6 [/SUP], Atsushi Yamanaka[SUP] 7 8 [/SUP], Yu Adachi[SUP] 3 [/SUP], Taishi Onodera[SUP] 3 [/SUP], Takashi Sato[SUP] 9 [/SUP], Masaharu Shinkai[SUP] 9 [/SUP], Ryosuke Suzuki[SUP] 10 [/SUP], Yoshiharu Matsuura[SUP] 5 6 [/SUP], Noritaka Hashii[SUP] 11 [/SUP], Yoshimasa Takahashi[SUP] 3 [/SUP], Takeshi Inoue[SUP] 1 [/SUP], Kazuo Yamashita[SUP] 4 [/SUP], Tomohiro Kurosaki[SUP] 1 12 13 [/SUP]
Affiliations
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.
. 2021 Dec 6;218(12):e20211003.
doi: 10.1084/jem.20211003. Epub 2021 Oct 8.
Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses
Ryo Shinnakasu[SUP] #[/SUP][SUP] 1 [/SUP], Shuhei Sakakibara[SUP] #[/SUP][SUP] 2 [/SUP], Hiromi Yamamoto[SUP] 1 [/SUP], Po-Hung Wang[SUP] 1 [/SUP], Saya Moriyama[SUP] 3 [/SUP], Nicolas Sax[SUP] 4 [/SUP], Chikako Ono[SUP] 5 6 [/SUP], Atsushi Yamanaka[SUP] 7 8 [/SUP], Yu Adachi[SUP] 3 [/SUP], Taishi Onodera[SUP] 3 [/SUP], Takashi Sato[SUP] 9 [/SUP], Masaharu Shinkai[SUP] 9 [/SUP], Ryosuke Suzuki[SUP] 10 [/SUP], Yoshiharu Matsuura[SUP] 5 6 [/SUP], Noritaka Hashii[SUP] 11 [/SUP], Yoshimasa Takahashi[SUP] 3 [/SUP], Takeshi Inoue[SUP] 1 [/SUP], Kazuo Yamashita[SUP] 4 [/SUP], Tomohiro Kurosaki[SUP] 1 12 13 [/SUP]
Affiliations
- PMID: 34623376
- DOI: 10.1084/jem.20211003
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.