Optimising a next generation exosome nano-vaccine platform

Novel vaccine platforms that can be rapidly bioengineered to combat variant and emerging viruses are urgently needed. This project will build on an established industrial collaboration to optimise exosomes as nano-vaccines to stimulate effective T-cell immunity. Exosomes are virus-sized extra-cellular vesicles. Our nano-vaccine platform inserts antigenic viral peptides into the CD63 protein that is incorporated into exosomes. As proof-of-principle we have shown these bioengineered exosomes can stimulate SARS-CoV-2-specific T-cell responses in vitro. The priority now is to optimise their immunogenicity thus generating broad, robust, and durable immunity to SARS-CoV-2 and other pathogens.
A key question is where to locate CD8+ and CD4+ T-cell epitopes within CD63 to maximise their immunogenicity when captured by different types of antigen presenting cells (APCs). In this project, the student will generate and characterise a library of exosome nano-vaccines. They will use EM and Cryo-EM to investigate the membrane orientation of CD63-inserted epitopes and fluorescent Super-Resolution microscopy to visualise exosome uptake by different APCs. Finally, our established panel of virus-specific T-cell clones will reveal how epitope positioning affects immunogenicity by different APCs. Collectively, the data will allow rational design of flexible next generation exosome nano-vaccines able to stimulate effective T-cell protection against disease.