Current vaccination strategies fail to induce protective immunity against global killers
such as HIV, malaria, tuberculosis and for cancer immunotherapy. A promising strategy is to
formulate antigens in nano/microparticles, rather than in soluble form. The reason for this is that particles are recognized by immune cells in a different way than soluble antigens and are capable of inducing antigen-specific cytotoxic T-cells that can recognize and eliminate infected or malignant cells. However, a major challenge remains efficient delivery of vaccine particles to the immune system. Furthermore, there is an urgent need for formulation strategies that encapsulate antigens under non-denaturating conditions, while allowing the antigen to be readily processed upon internalization by immune cells. To cope with these issues, we aim in this project to design dual (i.e. temperature and pH) responsive ultrasmall nanoparticles that encapsulate antigen under mild aqueous conditions via a simple temperature switch and expose their payload in the slightly acidic environment upon cellular uptake. The vaccine nanoparticles will be based on amphiphillic
block copolymers that self-assembly into sub 100 nm sized particles. Importantly, such ultrasmall particles can spontaneously (i.e. without the need of being transported by immune cells) migrate to the immune inducing sites in the draining lymph nodes. We hypothesize this will dramatically increase the efficiency of antigen delivery and the magnitude of the immune response.