(68d) Fabrication of Vaccines Based on Polymeric Microdisks to Enhance T Cell Immunity

Biomaterial vaccines offers unique opportunities to treat infectious disease and cancer. Interestingly, recent studies have found that the shape of synthetic vaccine carriers can impact their interactions with immune cells (e.g. macrophages, dendritic cells), leading to modulation of immune signaling and ultimately influencing the nature of immune response to a particular antigen.

In this work, we developed a disk-shaped polymeric vaccines through combining soft lithography with biodegradable polymers. The microdisks are generated by spin-coating poly(lactic-co-glycolic acid) (PLGA) solution mixed with toll-like receptor agonists 9 (i.e. CpG) and a model antigen (i.e. SIINFEKL) on a polydimethylsiloxane (PDMS) stamp with protruding micropillar array structures. Diameter of the microdisks, as well cargos (i.e. CpG and SIINFEKL) loadings, can be well controlled by the spin coating speed and the concentration of PLGA solution and cargos, allowing formation of microdisks with diameters of 1± 0.21 µm to 6.8±0.35 µm. These values correspond to aspect ratios of 5 to 35. Importantly, these disk-shaped vaccines allow control over the relative loading of each vaccine component, provide a route to alter both the geometric properties and the immunological signals included in the disks. In vitro studies are testing the capacity of microdisks to alter the activation and presentation of SIINFEKL in primary dendritic cells (DCs) and T cell co-culture. The ability of these materials to drive antigen specific responses in mice and during tumor challenge will also be presented. This work allows us to investigate the role of each vaccine signals, as well as their relative ratios in T cell immunity.