(61b) A Single-Shot Vaccination Using Stimuli-Responsive Nanoparticles for the Co-Delivery of Multi-Functional Payloads

In addition to the prolonged immune activation using polymeric antigen carriers, multi-faceted stimulation is crucial to the development of efficient and safe vaccines that reduce or circumvent the need for multiple doses. In this study, we developed a single-shot vaccine platform using stimuli-responsive, biodegradable nanoparticles made of acid-cleavable polyketals for the encapsulation of a broad range of antigens such as GFP, OVA, CBU1910 from Coxiella burnetii, and HA’s from influenza viruses. Surface-initiated photopolymerization synthesized the vaccine formulation that trapped multi-functional payloads of antigenic proteins and immunostimulatory adjuvants in the polymer network via attractive electrostatic interactions or specific affinity between His-tag (proteins) and Nickel-NTA (polyketal polymers). This vaccine design enabled the antigen release into the cytoplasm from the mildly acidic phago-lysosomes in antigen presenting cells (APCs), resulting in efficient and directed antigen presentation to T cells and the production of immunostimulatory cytokines (e.g., interferon-gamma [IFN-γ] and interleukin-4 [IL-4]), upon a single-shot administration. The novel vaccines developed in this study activated both humoral and cellular immunities and are capable of inducing desired immune response to bacterial and viral infections and can potentially be extended to other infectious diseases. This presentation will cover vaccine design, biomaterials synthesis, vaccine carrier preparation and characterization, and in vitro and in vivo validation on immune activation, and highlights the roles of interdisciplinary approaches and tool sets from engineering, chemistry, and biology in addressing a key challenge in human health.