SARS-CoV-2 RBD Scaffolded by AP205 or TIP60 Nanoparticles and Delivered as mRNA Elicits Robust Neutralizing Antibody...

Area of Science:

• Vaccinology
• Immunology
• Biotechnology

Background:

• SARS-CoV-2 receptor binding domain (RBD) based vaccines show promise.
• Multimeric RBD assemblies enhance antigen presentation and immune responses.
• Combining self-assembling scaffolds with mRNA delivery platforms for SARS-CoV-2 vaccines is underexplored.

Purpose of the Study:

• To design and evaluate novel self-assembling nanoparticles (AP205, TIP60) for presenting the SARS-CoV-2 RBD.
• To assess the immunogenicity and neutralization potency of mRNA vaccines encoding RBD fused to these new scaffolds.
• To compare the efficacy of these novel scaffolds against established RBD-ferritin constructs.

Main Methods:

• Designed RBD fused to AP205 and TIP60 self-assembling nanoparticles.
• Tested antigenicity of constructs via ELISA after transfection.
• Evaluated immunogenicity and neutralization potency in mice using mRNA delivery, with RBD-ferritin as comparator.

Main Results:

• Scaffolded RBD constructs were secreted and showed antigenicity.
• RBD-AP205 and RBD-TIP60 demonstrated robust antibody binding and neutralization titers in mice.
• Immune responses were comparable to RBD-ferritin and full-length spike protein vaccines.

Conclusions:

• AP205 and TIP60 nanoparticles effectively present RBD, inducing immune responses similar to ferritin.
• These novel scaffolds offer viable alternatives for multimeric display in mRNA vaccine design.
• The study provides new tools for developing advanced vaccine platforms.