386380 Design of Well-Defined Vaccines from Polyelectrolyte Multilayer Capsules
Challenging diseases such as cancer, HIV, and malaria could benefit from new prophylactic and therapeutic treatments that provide control over the type of immune responses that are elicited. However, vaccines are often formulated with mixtures of adjuvants, antigens, and excipients which may each contribute to the type of immune response that arises. In particular, many recent studies demonstrate that common biomaterials such as PLGA and polystyrene exhibit intrinsic immune activity. This characteristic creates a hurdle for more rational design of future vaccines because the role of the carrier itself may alter how other immune signals (e.g., antigens, adjuvants) are received by the immune system.
To overcome this challenge, we have developed a fully-defined vaccine composed entirely from self-assembled antigens and immune signals. Using a layer-by-layer process, immunogenic components were assembled onto sacrificial microparticles, followed by core removal to create a new type of polyelectrolyte multilayer (PEM) capsule. The resulting microcapsules exhibit loading levels proportional to the number of layers deposited and offer properties (e.g., size, loading, stability) that can be tuned by altering pH and ionic strength during synthesis and core removal. Capsules are efficiently taken up by primary dendritic cells (DCs) (bone marrow-derived) in a dose-dependent manner at levels up to 60%. Observation by laser confocal microscopy revealed capsules distributed throughout the interior of the cell as punctate structures. Corresponding flow cytometry studies demonstrate that capsules assembled from peptide antigen and immune signals efficiently activate DCs, as indicated by upregulation of activation and co-stimulatory surface markers. Ongoing studies are focused on presentation and binding affinity of peptide presented by treated DCs and the subsequent induction of antigen specific T cells in vitro and in vivo. The approach described here could lead to a platform for design of well-defined vaccines that allow better, more predictable induction of immunity.