Researchers in the lab of Dr. James Chou have engineered a new way to display membrane proteins to enhance vaccine immunogenicity using functionalized nanoparticles. The lab has successfully displayed several viral peptides using this technique and have demonstrated 3-4x stronger immune responses using the proteoliposome nanoparticle approach. The team hopes to expand the platform to other vaccine targets through industrial collaboration.

The discovery was made when researchers realized that membrane proteins critical for eliciting host immune response were not being recognized due to challenges in liposome assembly, the most common technique used for protein antigen presentation. These challenges include instability of the protein-liposome assemblies, and inability to control the orientation of the membrane protein, which is critical for antibody binding and subsequent immune signaling.

To overcome these issues, the lab sought to stabilize and fix the orientation of these protein-liposome assemblies by anchoring them to nanoparticles. The team accomplishes this by generating bicelles that contain a membrane protein functionalized with an affinity tag. This affinity tag then binds to its specific binding receptor located on the surface of the nanoparticle. Once enough proteins have been bound to the nanoparticle surface, the detergent can be removed, leaving behind a nanoparticle displaying many proteins in a unidirectional orientation.

This work was published in Angewandte Chemie.