Previously, high-aspect- ratio ribbon-like microconfetti (MC) composed of acetalated dextran (Ace-DEX) have been shown to form a subcutaneous depot for sustained drug release. In this study, MC were explored as an injectable vaccine platform. Production of MC by electrospinning followed by high-shear homogenization allowed for precise control over MC fabrication. Three distinct sizes of MC, small (0.67 × 10.2 μm2), medium (1.28 × 20.7 μm2), and large (5.67 × 90.2 μm2), were fabricated and loaded with the adjuvant, resiquimod. Steady release rates of resiquimod were observed from MC, indicating their ability to create an immunostimulatory depot in vivo. Resiquimod-loaded MC stimulated inflammatory cytokine production in bone marrow-derived dendritic cells without incurring additional cytotoxicity in vitro. Interestingly, even medium and large MC were able to be internalized by antigen-presenting cells and facilitate antigen presentation when ovalbumin was adsorbed onto their surface. After subcutaneous injection in vivo with adsorbed ovalbumin, blank MC of all sizes were found to stimulate a humoral response. Adjuvant activity of resiquimod was enhanced by loading it into MC and small- and medium-sized MC effectively induced a Th1-skewed immune response. Antigen co-delivered with adjuvant-loaded MC of various sizes illustrates a new potential vaccine platform.
Keywords: Ace-DEX; electrospinning; high aspect ratio; ovalbumin; resiquimod.