1. Acknowledgements Dept of Chemical Engineering, Monash Materials and Methods The core nanoparticles will be composed of mesoporous silica with the target size of around 300-500 nm by modification of commercially available colloidal silica with electrolyte. This synthesis process can be categorized as assembly of colloidal silica. The core nanoparticles and pDNA will be dispersed throughout a poly ‑ ε ‑ caprolactone (biodegradable polymer) matrix. Protein will be immobilized in core nanoparticles which are encapsulated by a biodegradable polymer where the pDNA vaccine prime is also encapsulated. Nanoparticle–Biodegradable Polymer Particles for Staged Delivery of a Prime–Boost Vaccination JENNY HO, Dr. GARETH M. FORDE, Dr. HUANTING WANG Department of Chemical Engineering, Melbourne, Victoria, 3800, Australia. Nanoparticle–Biodegradable Polymer Particles for Staged Delivery of a Prime–Boost Vaccination JENNY HO, Dr. GARETH M. FORDE, Dr. HUANTING WANG Department of Chemical Engineering, Melbourne, Victoria, 3800, Australia. The Problem Over 36 million children born every year do not have access to vaccines that are routinely given to children in the industrialized world as the lack of medical training and financial resources continues to impede the introduction of new vaccines to low-income countries. Additionally, the reuse of syringes and needles in the absence of sterilization exposes millions of people to infection. In some countries the proportion of injections given with syringes or needles reused without sterilization is as high as 70%. As a result, an inhalable particle capable of providing the staged delivery of a vaccine prime/boost would represent a major breakthrough in vaccine delivery technology. The use of plasmid DNA (pDNA) as an initial vaccine prime is gaining interest as it is non-infectious, encodes only the antigen of interest and does not contain heterologous protein components which the host may respond to. However, naked pDNA is not particularly suitable for direct injection as it is hindered by its instability in biological fluid and is degraded by serum nucleases. Thus, it is necessary to develop an efficient delivery system that can transfer pDNA into cells. The central challenge is to develop a cheap, simple delivery mechanism that can deliver pDNA safely to a patient while simultaneously obtaining high cell transfection efficiencies. The Objective The aim of this research is to produce a smart, multifunctional nanoparticle-biodegradable polymer particle for the staged delivery of a vaccine prime/booster after a single administration. The particle will have the potential to be administered orally or nasally. Plasmid DNA will be protected from degradation which will lead to increased transfection efficiencies and a subsequent reduction in the amount of pDNA required. The smart particles will be designed to deliver pDNA and proteins at discreet time intervals in order to achieve a pDNA- prime / protein-boost vaccination. Plasmid DNA Prime Biodegradable Polymer Matrix Colloidal Silica Mesoporous Silica Spectrum data for calcinated sample shown that the mesoporous silica contain mostly silica, sodium and chloride. Protein Boost Spectrum data for a calcinated sample shows that mesoporous silica consists mostly of silica, sodium and chloride