Self-assembling nanoparticle engineered from the ferritinophagy complex as a rabies virus vaccine candidate

Area of Science:

• Vaccinology
• Nanotechnology
• Immunology

Background:

• Ferritin-based vaccines show promise due to high immunogenicity and safety.
• Challenges include particle heterogeneity, improper assembly, and adaptor immunogenicity.
• Existing ferritin vaccine platforms require improvement for broader application.

Purpose of the Study:

• To develop a universal ferritin-based antigen delivery platform overcoming current limitations.
• To engineer an efficient ferritin-adaptor peptide for enhanced antigen presentation.
• To construct and evaluate a novel rabies virus (RABV) vaccine candidate.

Main Methods:

• Designed a ferritinophagy-adaptor (Fagy) peptide based on ferritinophagy complex structures.
• Conjugated Fagy-tagged rabies virus glycoprotein domain III (G_DIII) to ferritin nanoparticles.
• Assessed vaccine homogeneity, stability, immunogenicity, and in vivo protection in a mouse model.

Main Results:

• The Fagy-tag demonstrated high binding affinity to ferritin nanoparticles, ensuring efficient antigen presentation.
• The self-assembling RABV vaccine candidate exhibited superior homogeneity, stability, and immunogenicity.
• A single dose induced potent, rapid, and durable immune responses, protecting mice against RABV challenge.

Conclusions:

• The engineered Fagy-tag provides a universal platform for ferritin-based vaccine development.
• This strategy overcomes previous challenges, enabling stable and highly immunogenic nanoparticle vaccines.
• The platform holds significant potential for creating vaccines against various pathogens and diseases.