(619b) Exploiting Lymphatic Transport And Complement Activation In Nanoparticle Vaccines

The development of vaccine technologies has emerged as a forefront healthcare initiative, especially technologies for use in developing countries, posing severe economic and logistic constraints. One must develop antigen targeting and adjuvant schemes that respectively facilitate delivery of antigen to dendritic cells (DCs) and elicit their activation. Here we engineered antigen-bearing nanoparticle vaccines with two novel features: lymph node-targeting and in situ complement activation. Following intradermal injection, interstitial flow transported our ultra-small nanoparticles (25 nm) highly efficiently into lymphatic capillaries and their draining lymph nodes, targeting half of the DCs there, whereas nanoparticles even 100 nm large were only 10% as efficient. Furthermore, the surface chemistry of our nanoparticles activated the complement cascade, which spontaneously generated a danger signal in situ and potently activated DCs. With ovalbumin as a model antigen conjugated to the nanoparticles, we demonstrated humoral and cellular immunity in mice in a highly size-dependent and complement-dependent manner. This simple formulation harnessing particle nanotechnology and biofunctionalization may provide an elegant vaccine technology platform for applications that include global health due to the rugged stability and molecular simplicity of the materials employed. Our results point to lymph node targeting and complement activation as potentially important strategies in vaccine design.