Developing synthetic multivalent cellular effectors

Abstract

I have designed bioconjugates that can elicit desired cellular responses – cellular effectors. Using multivalent interactions, involving the simultaneous binding of multiple receptors to multiple ligands, I have designed cellular effectors to use as vaccines and to direct stem cell fate. I have developed multivalent scaffolds to be used as a “universal” influenza vaccine, vaccine constructs for Respiratory Syncytial Virus (RSV) that do not present the variable antigenic site Ø, developed a novel strategy for nanopatterning protein antigens to guide the immune response toward and away from desired epitopes, and generated polypeptide-based scaffolds that can explicitly control the valency of multivalent conjugates as well as the inter-ligand spacing and used these to direct stem cell fate. All of these systems have shown that by controlling the nanoscale presentation of ligands, the system response can be altered and directed toward a desired behavior. The scaffolds that I have developed can be used in other vaccine design and stem cell proliferation studies. The general application of nanopatterning protein antigens has already been applied to several other systems in our lab and we hypothesize that it will be broadly applicable in future antigen design studies. Thus, the work presented in this thesis will stand as a foundation for future studies in vaccine design and cell signaling studies.