RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response

• Published in: Signal transduction and targeted therapy Vol. 5; no. 1; p. 282
• Main Authors: Liu, Zezhong, Xu, Wei, Xia, Shuai, Gu, Chenjian, Wang, Xinling, Wang, Qian, Zhou, Jie, Wu, Yanling, Cai, Xia, Qu, Di, Ying, Tianlei, Xie, Youhua, Lu, Lu, Yuan, Zhenghong, Jiang, Shibo
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 27.11.2020; Nature Publishing Group UK
• Subjects: Angiotensin-Converting Enzyme 2 - antagonists & inhibitors; Angiotensin-Converting Enzyme 2 - immunology; Animals; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - pharmacology; Coronaviruses; COVID-19; COVID-19 - drug therapy; COVID-19 - immunology; COVID-19 - virology; COVID-19 vaccines; COVID-19 Vaccines - immunology; COVID-19 Vaccines - pharmacology; Epitopes - immunology; Humans; Immunoglobulin Fc Fragments - immunology; Immunoglobulin Fc Fragments - pharmacology; Mice; Mice, Inbred BALB C; Pandemics; Protein Binding - drug effects; Protein Binding - immunology; Receptors, Virus - genetics; Receptors, Virus - immunology; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - antagonists & inhibitors; Spike Glycoprotein, Coronavirus - immunology
• ISSN: 2059-3635; 2095-9907; 2059-3635
• DOI: 10.1038/s41392-020-00402-5

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.