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Protocol for Recombinant RBD-based SARS Vaccines: Protein Preparation, Animal Vaccination and Neutralization Detection
Published on: May 2, 2011
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Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens
Marcos C Miranda1,2, Elizabeth Kepl1,2, Mary Jane Navarro1
1Department of Biochemistry, University of Washington, Seattle, WA, USA.
NPJ Vaccines
|October 8, 2024
Summary
The two-component protein nanoparticle (RBD-NP) vaccine platform shows potential for broad protection against SARS-CoV-2 variants. This platform can be rapidly adapted and stabilized for variant-specific vaccine development, eliciting robust neutralizing antibody responses.
Area of Science:
- Vaccinology
- Protein Nanoparticle Technology
- Coronaviruses
Background:
- A two-component protein nanoparticle vaccine (RBD-NP) displaying SARS-CoV-2 spike protein receptor-binding domains (RBDs) has demonstrated efficacy.
- This platform, when adjuvanted, elicited strong immune responses in clinical trials and is licensed as SKYCovione™.
Purpose of the Study:
- To characterize biophysical properties, stability, antigenicity, and immunogenicity of RBD-NP immunogens with mutations from SARS-CoV-2 variants (B.1.351, P.1, Omicron BA.5, XBB.1.5).
- To assess the platform's adaptability and stabilization for variant vaccine development and compare it with other immunogen types.
Main Methods:
- Characterization of RBD-NP immunogens incorporating variant mutations (β, γ, E484K, Omicron BA.5, XBB.1.5).
- Comparison of variant RBD-NPs with Wu-1 RBD-NPs and soluble prefusion-stabilized (HexaPro) spike trimers.
- Assessment of physical stability through introduced mutations and evaluation of immunogenicity and neutralizing antibody responses against various SARS-CoV-2 variants.
Main Results:
- Properties of variant-based immunogens varied significantly, impacting development viability.
- Stabilizing mutations in RBD-NPs enhanced physical stability without compromising immunogenicity.
- RBD-NP immunogens and HexaPro trimers induced comparable neutralizing antibody levels against diverse SARS-CoV-2 variants.
Conclusions:
- The RBD-NP platform can be rapidly designed and stabilized to elicit neutralizing antibodies against SARS-CoV-2 variants.
- This demonstrates the potential of two-component RBD-NPs for developing broadly protective coronavirus vaccines.
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