RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response
Top Cited Papers
Open Access
- 27 November 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Signal Transduction and Targeted Therapy
- Vol. 5 (1), 1-10
- https://doi.org/10.1038/s41392-020-00402-5
Abstract
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.Keywords
Funding Information
- National Natural Science Foundation of China ((82041025 to S.J., 81822045 to L.L., 81822045 to L.L.)
This publication has 50 references indexed in Scilit:
- Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyondTrends in Microbiology, 2015
- Current advancements and potential strategies in the development of MERS-CoV vaccinesExpert Review of Vaccines, 2014
- Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndromeExpert Review of Vaccines, 2012
- Strategies for extended serum half-life of protein therapeuticsCurrent Opinion in Biotechnology, 2011
- Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunityVirology, 2009
- The spike protein of SARS-CoV — a target for vaccine and therapeutic developmentNature Reviews Microbiology, 2009
- Fcγ receptors as regulators of immune responsesNature Reviews Immunology, 2008
- Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal modelVaccine, 2007
- Cross-Neutralization of Human and Palm Civet Severe Acute Respiratory Syndrome Coronaviruses by Antibodies Targeting the Receptor-Binding Domain of Spike ProteinThe Journal of Immunology, 2006
- Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccineBiochemical and Biophysical Research Communications, 2004