(596f) Impact of Dose, Route, and Composition on the Immunogenicity of Polyelectrolyte Multilayers Assembled on Gold Templates

Novel biomaterial vaccines are promising in treating challenging diseases such as cancer and infectious diseases. We recently developed a vaccine platform based on self-assembly of immune signals into immune polyelectrolyte multilayer (iPEMs). These iPEMs vaccine can be delivered on gold nanoparticle template to stimulate effector cytokines in vitro and expand antigen-specific T cells in vivo. Here we investigate the impact of vaccine dose, route, and adjuvant choice on the generation of T cell immunity and anti-tumor response. Three injection routes (i.e. intradermal, subcutaneous and intramuscular injections) and three iPEM dosing levels were employed. Intradermal injection induced the most potent antigen-specific T cell responses, and in all cases, the level of response was dose dependent. Importantly, we discovered that iPEMs generate durable memory T cells responses, indicated by potent, antigen-specific CD8⁺ T cells responses in mice receiving a vaccine challenge 70 days after a priming immunization. In a common exogenous antigen melanoma model, iPEM vaccines inhibited tumor growth more effectively than equivalent admixed formulations consisting of antigen and one of several toll like receptor agonists used as adjuvants. This study reveals the ability of iPEMs to enhance response to several different classes of vaccine cargos using common injection routes, creating a new vaccine and adjuvant delivery platform based entirely on immune signals.