Development of Glycan-masked SARS-CoV-2 RBD vaccines against SARS-related coronaviruses
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.
Authors
- Zuxin Liang
- Huiping Shi (ORCID: https://orcid.org/0000-0002-4727-9999)
- Guoguo Ye
- Xiaohua Gong (ORCID: https://orcid.org/0000-0003-2074-1802)
- Yushan Jiang (ORCID: https://orcid.org/0000-0001-8263-3423)
- Abid Hussain (ORCID: https://orcid.org/0000-0002-0640-4730)
- Yuanyu Huang (ORCID: https://orcid.org/0000-0003-3935-7245)
- Minghui Yang (ORCID: https://orcid.org/0009-0004-2196-2556)
- Chenguang Shen (ORCID: https://orcid.org/0000-0001-8607-3750)
- Yang Yang (ORCID: https://orcid.org/0000-0002-6489-4459)
- Chunhui Li (ORCID: https://orcid.org/0000-0002-4213-3923)
- Yuxin Tian (ORCID: https://orcid.org/0009-0001-5434-0946)
- Mengjun Li (ORCID: https://orcid.org/0000-0003-4426-4684)
- Mengyuan Zhao (ORCID: https://orcid.org/0000-0003-4662-2975)
- Wei Guang Zhao (ORCID: https://orcid.org/0000-0002-7887-2357)
Institutions
- Beijing Institute of Technology (CN)
- Anhui Medical University (CN)
- Southern University of Science and Technology (CN)
- Zhujiang Hospital (CN)
- Shenzhen Third People’s Hospital (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- PLoS Pathogens
- Published
- 2024-09-26
- DOI
- https://doi.org/10.1371/journal.ppat.1012599
- Citations
- 7
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.72
Funders
- National Natural Science Foundation of China
- Beijing Institute of Technology
- Beijing Institute of Technology Research Fund Program for Young Scholars
- Science and Technology Planning Project of Guangdong Province
- Basic and Applied Basic Research Foundation of Guangdong Province