An Immunoreceptor-Targeting Strategy with Minimalistic C3b Peptide Fusion Enhances SARS-CoV-2 RBD mRNA Vaccine...

Area of Science:

• Immunology
• Vaccinology
• Molecular Biology

Background:

• The COVID-19 pandemic highlighted mRNA vaccine efficacy.
• Enhancing mRNA vaccine immunogenicity is crucial for broader applications.
• Antigen fusion proteins can improve immune cell targeting and humoral immunity.

Purpose of the Study:

• To investigate a novel mRNA vaccine strategy using antigen fusion proteins.
• To evaluate the immunogenicity of SARS-CoV-2 receptor binding domain (RBD) fused with a complement C3b peptide (RBD-mC3).
• To compare RBD-mC3 with RBD-Fc and wild-type RBD formulations for immune response.

Main Methods:

• Western blot and immunofluorescence assays to confirm antigenicity and receptor targeting.
• Development of mRNA vaccine formulations expressing RBD-mC3, RBD-Fc, and wild-type RBD.
• Mouse immunization studies to assess antibody responses and vaccine immunogenicity.

Main Results:

• RBD-mC3 demonstrated proper antigenicity and functionality, targeting complement receptor 1 (CR1).
• Both RBD-mC3 and RBD-Fc formulations enhanced vaccine immunogenicity compared to wild-type RBD.
• RBD-mC3 elicited more sustained RBD-specific antibody titers than RBD-Fc.

Conclusions:

• A novel C3b-based antigen design strategy effectively enhances mRNA vaccine immunogenicity.
• Fusion of RBD with a minimalistic C3b peptide segment offers a promising approach for targeted vaccine development.
• The RBD-mC3 strategy shows potential for improved and sustained immune responses against viral antigens.