Tuning innate immune function using microneedles containing multiple classes of toll-like receptor agonists

Area of Science:

• Immunology
• Nanotechnology
• Vaccine Development

Background:

• Microneedle arrays (MNAs) offer efficient, painless skin penetration for accessing immune cells.
• Clinical interest in MNA-based vaccines is high due to their ability to target immune-rich skin niches.
• Immune polyelectrolyte multilayers (iPEMs) are nanostructures built from immune signals using electrostatic self-assembly.

Purpose of the Study:

• To develop MNA-based vaccines utilizing iPEMs for ultra-high density delivery of antigens and toll-like receptor agonists (TLRAs).
• To investigate the controlled activation of specific immune pathways by varying TLRAs in MNA formulations.
• To evaluate the impact of MNA-delivered TLRAs on T cell responses in vitro and in vivo.

Main Methods:

• Fabrication of MNAs loaded with peptide antigens and negatively charged TLRAs.
• Utilizing electrostatic self-assembly to create dense nanostructure arrays (iPEMs).
• Assessing antigen-specific T cell activation and proliferation in vitro.
• Conducting in vivo vaccine studies to analyze T cell responses based on TLRAs composition.

Main Results:

• Facile assembly of iPEMs on MNAs, enabling signal transduction through respective TLR pathways.
• Demonstrated activation of primary antigen-presenting cells and proliferation of antigen-specific T cells.
• In vivo studies showed distinct T cell responses correlated with the number of TLRA classes delivered via MNAs.

Conclusions:

• MNA technology enables high-density delivery of nanostructured vaccine components.
• This platform allows for probing the integration of multiple TLRAs in skin to precisely tune immune responses.
• The developed MNA-iPEM system holds promise for advanced vaccine design and immunotherapy.