Engineered Curli Nanofilaments as a Self-Adjuvanted Antigen Delivery Platform

Area of Science:

• Biotechnology
• Immunology
• Materials Science

Background:

• Proteinaceous nanoparticles are effective antigen delivery systems for vaccines.
• Current nanovaccines often require coadministration with adjuvants for robust immune responses.
• Curli-specific gene A (CsgA) protein self-assembles into immunostimulatory nanofilaments.

Purpose of the Study:

• To engineer an intrinsically immunostimulatory antigen delivery platform using CsgA.
• To develop a self-adjuvanted nanovaccine for influenza.
• To evaluate the immunogenicity and protective efficacy of CsgA-based nanovaccines.

Main Methods:

• Engineered CsgA protein with M2e antigen sequences were designed.
• Chimeric 3M2e-CsgA self-assembled into cross-β-sheet nanofilaments.
• Nanofiber immunogenicity and protective efficacy were assessed in mice models.

Main Results:

• Self-assembled 3M2e-CsgA nanofilaments activated toll-like receptors 2 and 1.
• Nanofibers were internalized by antigen-presenting cells, promoting dendritic cell maturation.
• CsgA-based nanovaccines induced robust humoral and cellular immunity, conferring complete protection against H1N1 influenza.
• No overt systemic inflammation or reactogenicity was observed.

Conclusions:

• Engineered CsgA nanostructures serve as self-adjuvanted, safe, and versatile antigen delivery systems.
• This platform holds significant potential for developing next-generation vaccines against infectious diseases.
• CsgA-based nanovaccines offer a promising alternative to traditional vaccine formulations requiring external adjuvants.