(43b) Nanoparticle Design for Vaccine Delivery

Nanoparticulate carriers enable the site specific delivery for controlled response and can harness the innate pathways by which the body responds to natural invaders; nanoparticles are an inherent size to associate with antigen presenting cells (APCs) and also facilitate the co-delivery of antigen and adjuvants to mimic a pathogenic interaction. While much is known about desired nanoparticle design for systemic intravenous administration, less is known about nanoparticle design parameters critical to vaccine-oriented routes of administration; intramuscular, dermal and pulmonary routes all offer benefits by nanoparticle delivery for creating enhanced local and systemic protection.  Using a nano-molding technique, PRINT (Particle Replication In Non-wetting Templates), we modulated particle characteristics to tailor APC uptake and explored particle features for intended immunological responses.  Cargo-free un-modified PRINT hydrogel particles were found to be immunologically inert in the airways of mice; at seven days, particles were found in the lung without airway remodeling or triggering of host immunity by either pro-inflammatory cytokine production or cellular recruitment.  However, specific modification of the surface of these particles was shown to engender antigen-specific responses.  Ovalbumin, a model antigen, was covalently bound to the particle surface using a heterobifunctional PEG linker and this particulate form was found to elicit an ova-specific immune response following in vivo foot pad immunization.  These data suggest that, while PRINT particles themselves are not immunostimulatory, rational particle designs can lead to enhanced responses by balancing uptake into APCs, antigen presentation, and trafficking to lymph nodes.