Targeting the Innate Immune System Using Protein Design

Abstract

Subunit vaccines require adjuvants to create a robust immune response. Adjuvants are limited by formulation difficulties and the types of immune responses they elicit. There is a need for a new generation of adjuvants. An ideal adjuvant would be easy to characterize with a protein antigen, hyperstable, specific to a defined immune pathway, and easily modified. In this thesis, I describe the application of protein design to create protein based adjuvants. We created novel minibinders that can be linked together to agonize TLR3. Additional stories are presented which describe the efforts to create protein binders for TLR5, TREM-2, and FcγRIIA.