Tough and waterproof microneedles overcome mucosal immunotolerance by modulating antigen release patterns

Area of Science:

• Vaccinology
• Nanotechnology
• Immunology

Background:

• Mucosal vaccines are ideal for mucosal pathogens but face challenges like low immunogenicity and poor antigen delivery.
• Mucosal tolerance, a significant hurdle, often limits the efficacy of subunit vaccines administered via mucosal routes.

Purpose of the Study:

• To develop a buccal microneedle patch with engineered nanoparticles for delivering the urease B subunit (rUreB).
• To overcome challenges in mucosal subunit vaccine development, including low immunogenicity, poor delivery, and mucosal tolerance.

Main Methods:

• Engineered nanoparticles were designed to protect the antigen and control its release profile.
• Nanoparticles were incorporated into microneedle tips with enhanced mechanical and waterproof properties for buccal mucosa penetration and resistance to salivary washout.
• An S-curve antigen release pattern was achieved to modulate immune cell recruitment and tolerance.

Main Results:

• The microneedle patch demonstrated effective penetration of the buccal mucosa and resistance to salivary washout.
• An S-curve antigen release profile was observed, promoting antigen-presenting cell (APC) recruitment and downregulating tolerogenic dendritic cells (DCs) and regulatory T cells (Tregs).
• The vaccine induced potent systemic and mucosal immune responses, providing superior protection against oral Helicobacter pylori challenge in mice without immune stimulators.

Conclusions:

• The rationally designed buccal microneedle vaccine effectively overcomes mucosal delivery barriers and mucosal tolerance.
• This microneedle-based approach offers a promising alternative strategy for mucosal vaccination of subunit antigens.
• The developed system demonstrates potential for enhanced protection against mucosal pathogens.