A Biomimetic Multi-Component Subunit Vaccine via Ratiometric Loading of Hierarchical Hydrogels

The development of subunit vaccines that mimic the molecular complexity of attenuated vaccines has been limited by the difficulty in reliably delivering multiple chemically diverse payloads at controllable concentrations. We report on hydrogels that use a single homopolymer structure of poly(propylene sulfone) to enable the ratiometric loading of a protein antigen and four physicochemically distinct adjuvants in a hierarchical manner. The optimized vaccine consisted of immunostimiulants that were either adsorbed to or encapsulated within nanogels, which were capable of noncovalent anchoring to subcutaneous tissues via protein-affinity coronas. These 5-component nanogel vaccines demonstrated enhanced humoral and cell-mediated immune responses compared to formulations with standard single adjuvant and antigen pairing. The use of a single simple homopolymer capable of rapid and stable loading and deliver of diverse molecular cargoes holds promise for facile development and optimization of scalable subunit vaccines and complex therapeutic formulations for a wide range of biomedical applications.