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Updated: Nov 28, 2025
Protocol for Recombinant RBD-based SARS Vaccines: Protein Preparation, Animal Vaccination and Neutralization Detection
Published on: May 2, 2011
RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response
Zezhong Liu1, Wei Xu1, Shuai Xia1
1Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and BSL-3 facility, Fudan University, Shanghai, 200032, China.
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.
Insights
A novel SARS-CoV-2 subunit vaccine using the receptor-binding domain (RBD) and human IgG Fc fragment demonstrated potent neutralizing antibodies against COVID-19 and its variants in mice.
Area of Science:
- Immunology
- Virology
- Vaccine Development
Background:
- The COVID-19 pandemic necessitates urgent development of effective vaccines.
- The SARS-CoV-2 spike protein's RBD is a key target for neutralizing antibodies.
- RBD contains critical epitopes for vaccine design against SARS-CoV-2.
Purpose of the Study:
- To evaluate a novel subunit vaccine candidate composed of SARS-CoV-2 RBD and human IgG Fc fragment.
- To assess the immunogenicity and protective efficacy of the RBD-Fc vaccine in preclinical models.
- To determine the breadth of neutralization against SARS-CoV-2 variants and related coronaviruses.
Main Methods:
- Immunization of mice with the SARS-CoV-2 RBD-Fc subunit vaccine.
- Measurement of RBD-specific antibody titers and neutralizing activity against pseudotyped and live SARS-CoV-2.
- Testing cross-neutralization against SARS-CoV-2 variants and SARS-related coronaviruses (SARSr-CoVs).
- Challenging human ACE2 transgenic mice vaccinated with RBD-Fc.
Main Results:
- High titers of RBD-specific antibodies with robust neutralizing activity were elicited.
- The vaccine-induced antibodies neutralized SARS-CoV-2 variants and SARSr-CoVs.
- Vaccinated human ACE2 transgenic mice showed protection against SARS-CoV-2 challenge.
- The RBD-Fc vaccine demonstrated potential for broad-spectrum protection.
Conclusions:
- The SARS-CoV-2 RBD-Fc vaccine candidate is immunogenic and protective in preclinical studies.
- This vaccine shows potential for broad-spectrum efficacy against current and future coronaviruses.
- RBD-Fc represents a promising platform for developing effective COVID-19 vaccines and countermeasures against emerging coronaviruses.
