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

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

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.