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

• Published in: The 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
• Language: English
• Published: United States Rockefeller University Press 06.12.2021
• Subjects: 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
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20211003

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.