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

SARS-CoV-2 受体结合域的聚糖工程可引发针对 SARS 相关病毒的交叉中和抗体

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作者: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, Tomohi

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.

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