tetano
Editor, Senior Moderator
PLoS Pathog
. 2024 Sep 26;20(9):e1012599.
doi: 10.1371/journal.ppat.1012599. Online ahead of print. Development of Glycan-masked SARS-CoV-2 RBD vaccines against SARS-related coronaviruses
Zuxin Liang[SUP] 1 [/SUP], Chunhui Li[SUP] 2 [/SUP], Xiaohua Gong[SUP] 3 4 [/SUP], Guoguo Ye[SUP] 3 [/SUP], Yushan Jiang[SUP] 1 [/SUP], Huiping Shi[SUP] 2 [/SUP], Abid Hussain[SUP] 2 [/SUP], Mengyuan Zhao[SUP] 2 [/SUP], Mengjun Li[SUP] 1 [/SUP], Yuxin Tian[SUP] 2 [/SUP], Wei Zhao[SUP] 1 [/SUP], Yang Yang[SUP] 3 [/SUP], Yuanyu Huang[SUP] 2 [/SUP], Chenguang Shen[SUP] 1 [/SUP], Minghui Yang[SUP] 2 [/SUP]
Affiliations
Emerging and recurrent infectious diseases caused by coronaviruses remain a significant public health concern. Here, we present a targeted approach to elicit antibodies capable of neutralizing SARS-CoV-2 variants and other SARS-related coronaviruses. By introducing amino acid mutations at mutation-prone sites, we engineered glycosylation modifications to the Receptor Binding Domain (RBD) of SARS-CoV-2, thereby exposing more conserved, yet less accessible epitopes. We developed both messenger RNA (mRNA) and recombination subunit vaccines using these engineered-RBDs (M1, M2) and the wild-type RBD as immunogens. The engineered-RBD vaccines elicited robust neutralizing responses against various SARS-CoV-2 variants as well as SARS-CoV and WIV1-CoV, and conferred protection in mice challenged with the XBB.1.16 strain. Furthermore, We highlighted that glycan masking is a decisive factor in antibody binding changes and RBD-conserved antibody response. Additionally, the glycan-engineered RBD mRNA vaccines stimulated stronger cell-mediated immune responses. Our glycan modification strategy significantly enhances broad-spectrum neutralizing efficacy and cellular immunity, providing valuable insights for the development of vaccines against a wide range of SARS-related coronaviruses.
. 2024 Sep 26;20(9):e1012599.
doi: 10.1371/journal.ppat.1012599. Online ahead of print. Development of Glycan-masked SARS-CoV-2 RBD vaccines against SARS-related coronaviruses
Zuxin Liang[SUP] 1 [/SUP], Chunhui Li[SUP] 2 [/SUP], Xiaohua Gong[SUP] 3 4 [/SUP], Guoguo Ye[SUP] 3 [/SUP], Yushan Jiang[SUP] 1 [/SUP], Huiping Shi[SUP] 2 [/SUP], Abid Hussain[SUP] 2 [/SUP], Mengyuan Zhao[SUP] 2 [/SUP], Mengjun Li[SUP] 1 [/SUP], Yuxin Tian[SUP] 2 [/SUP], Wei Zhao[SUP] 1 [/SUP], Yang Yang[SUP] 3 [/SUP], Yuanyu Huang[SUP] 2 [/SUP], Chenguang Shen[SUP] 1 [/SUP], Minghui Yang[SUP] 2 [/SUP]
Affiliations
- PMID: 39325829
- DOI: 10.1371/journal.ppat.1012599
Emerging and recurrent infectious diseases caused by coronaviruses remain a significant public health concern. Here, we present a targeted approach to elicit antibodies capable of neutralizing SARS-CoV-2 variants and other SARS-related coronaviruses. By introducing amino acid mutations at mutation-prone sites, we engineered glycosylation modifications to the Receptor Binding Domain (RBD) of SARS-CoV-2, thereby exposing more conserved, yet less accessible epitopes. We developed both messenger RNA (mRNA) and recombination subunit vaccines using these engineered-RBDs (M1, M2) and the wild-type RBD as immunogens. The engineered-RBD vaccines elicited robust neutralizing responses against various SARS-CoV-2 variants as well as SARS-CoV and WIV1-CoV, and conferred protection in mice challenged with the XBB.1.16 strain. Furthermore, We highlighted that glycan masking is a decisive factor in antibody binding changes and RBD-conserved antibody response. Additionally, the glycan-engineered RBD mRNA vaccines stimulated stronger cell-mediated immune responses. Our glycan modification strategy significantly enhances broad-spectrum neutralizing efficacy and cellular immunity, providing valuable insights for the development of vaccines against a wide range of SARS-related coronaviruses.