Developing novel vaccine formulations for single-dose immunisation

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Almost all current vaccines require administration in two or three doses and at specific time intervals to achieve full efficacy. Single dose immunisation is a long-standing concept that could significantly improve vaccination coverage globally. Attempts to develop a single dose vaccine have so far been unsuccessful with one of the key obstacles being the design of formulations capable of achieving pulsatile (time-determined) vaccine release in vivo, while preserving antigen stability and immunogenicity. This project aims to develop vaccine delivery formulations that would allow prime-boost vaccination to be combined into a single dose by encapsulating the booster vaccine into microparticles and administering it together with the priming vaccine in soluble form. The timing and kinetics of the booster vaccine release will be determined by the chemical composition and method of preparation. A particular focus will be placed on utilising novel production techniques to develop delivery formulations (particles or gels) to stabilise the vaccine antigen in vivo. Various biocompatible polymers with a range of degradation profiles will be used to produce particles with different kinetics (continuous/pulsatile) and time to antigen release. Following in vitro analysis of particle size, monodispersity, encapsulation efficiency and release kinetics under simulated "in vivo" conditions, new formulations will be tested in vivo for pharmacokinetics, safety and immunogenicity. Development of novel formulation and particle production will encompass process validation and explore scale-up and suitability for GMP production. Initially the formulations will be optimised using a model antigen and will then move to testing the process using two of the currently most promising vaccine platforms, virus like particles (VLPs) and viral vectors. Successful formulations will be taken forward into mouse disease challenge models and compared with standard prime-boost regimens. This project has emphasis on chemical composition and formulation and the ideal candidate will have background in chemistry or pharmacology.