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Neutralizing Potency of Prototype and Omicron RBD mRNA Vaccines Against Omicron Variant
Jinkai Zang1, Yannan Yin1, Shiqi Xu1
1CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Abstract:
The newly emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains more than 30 mutations on the spike protein, 15 of which are located within the receptor binding domain (RBD). Consequently, Omicron is able to extensively escape existing neutralizing antibodies and may therefore compromise the efficacy of current vaccines based on the original strain, highlighting the importance and urgency of developing effective vaccines against Omicron. Here we report the rapid generation and evaluation of an mRNA vaccine candidate specific to Omicron, and explore the feasibility of heterologous immunization with WT and Omicron RBD vaccines. This mRNA vaccine encodes the RBD of Omicron (designated as RBD-O) and is formulated with lipid nanoparticle. Two doses of the RBD-O mRNA vaccine efficiently induce neutralizing antibodies in mice; however, the antisera are effective only on the Omicron variant but not on the wildtype and Delta strains, indicating a narrow neutralization spectrum. It is noted that the neutralization profile of the RBD-O mRNA vaccine is opposite to that observed for the mRNA vaccine expressing the wildtype RBD (RBD-WT). Importantly, booster with RBD-O mRNA vaccine after two doses of RBD-WT mRNA vaccine can significantly increase neutralization titers against Omicron. Additionally, an obvious increase in IFN-γ, IL-2, and TNF-α-expressing RBD-specific CD4+ T cell responses was observed after immunization with the RBD-WT and/or RBD-O mRNA vaccine. Together, our work demonstrates the feasibility and potency of an RBD-based mRNA vaccine specific to Omicron, providing important information for further development of heterologous immunization program or bivalent/multivalent SARS-CoV-2 vaccines with broad-spectrum efficacy.
Insights
A new mRNA vaccine targeting the Omicron variant (RBD-O) shows promise. While effective against Omicron, it has a narrow neutralization spectrum. Heterologous immunization with wildtype (RBD-WT) and Omicron vaccines boosts Omicron-specific immunity.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- The Omicron variant of SARS-CoV-2 possesses numerous spike protein mutations, particularly in the RBD, leading to significant immune evasion.
- Existing vaccines may have reduced efficacy against Omicron due to its extensive antibody escape properties.
- Development of Omicron-specific vaccines is crucial for public health.
Purpose of the Study:
- To rapidly generate and evaluate an mRNA vaccine candidate targeting the Omicron receptor binding domain (RBD-O).
- To explore the feasibility of heterologous immunization strategies using wildtype (RBD-WT) and Omicron RBD vaccines.
- To assess the immunogenicity and neutralization breadth of Omicron-specific mRNA vaccines.
Main Methods:
- Development of an mRNA vaccine encoding the Omicron RBD (RBD-O) formulated with lipid nanoparticles.
- Immunization of mice with two doses of RBD-O mRNA vaccine.
- Evaluation of neutralizing antibody responses against Omicron, wildtype, and Delta SARS-CoV-2 strains.
- Assessment of T cell responses (IFN-γ, IL-2, TNF-α) in immunized mice.
- Investigation of heterologous immunization by boosting RBD-WT vaccinated mice with RBD-O.
Main Results:
- Two doses of RBD-O mRNA vaccine induced neutralizing antibodies effective against Omicron but not wildtype or Delta strains.
- The neutralization profile of RBD-O vaccine was distinct from the RBD-WT vaccine.
- Booster immunization with RBD-O after RBD-WT vaccination significantly enhanced neutralization titers against Omicron.
- RBD-specific CD4+ T cell responses, including IFN-γ, IL-2, and TNF-α production, were observed.
Conclusions:
- An RBD-O mRNA vaccine candidate is feasible and potent for targeting the Omicron variant.
- Heterologous immunization strategies combining WT and Omicron vaccines show potential for broadening immune responses.
- Findings support the development of bivalent/multivalent vaccines for broad-spectrum SARS-CoV-2 efficacy.
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