Building and utilizing protein-based nanoparticles to modulate immune pathways

Abstract

The goal of vaccines is to appropriately stimulate the immune system to elicit potent and long-term protection against each pathogen. Current vaccines boost immune activation with adjuvants, which most commonly consist of oil-in-water emulsions despite the fact that the mechanisms of action of these adjuvants are not fully understood. Recent research has turned to molecular adjuvants with the aim of tuning the immune system with greater precision. However, these approaches are currently limited by the lack of platforms that can systematically test an antigen alongside immune-activating proteins. Control over the spatial arrangement and combination of immune ligands is needed to better understand how to modulate the complex immune responses surrounding an antigen of interest. Protein design has enabled the creation of two-component, self-assembling protein nanocages that serve as scaffolds for displaying functional domains, including antigens, antibodies, and immune proteins. The goal of my research is to leverage these two-component protein nanoparticle platforms to identify immune-modulatory proteins that can enhance the potency of nanoparticle immunogens and to develop a new platform capable of driving immune cell colocalization to activate juxtacrine signaling.