The use of monoclonal antibodies (mAbs) as therapeutics (immunotherapy) has been highly successful for a number of diseases. MAbs offer an advantage of being highly specific, with little adverse effects. Furthermore, mAbs can engage in Fc-related functions that may serve to promote clearance of infections. We have been using state-of-the-art protein engineering methods to identify, characterize, and evaluate novel immunotherapies against Ebola virus, Chikungunya virus, and Crimean-Congo Hemorrhagic Fever virus. We focus on developing new therapeutics by protein engineering that may have features that are not possible with conventional (natural) antibodies.

Dengue virus is a mosquito-transmitted flavivirus that causes hundreds of millions of human infections world-wide each year. There are four serotypes of Dengue (DENV1-4) that co-circulate in hyperendemic regions.  Dengue virus vaccine design has been complicated by the emergence of Zika virus (ZIKV), another flavivirus. We have been using structure-guided protein engineering to develop novel immunogens that elicit DENV and ZIKV protective antibody responses.  Our strategy focuses on common susceptible epitopes that may be structurally engineered.

Phage display is a combinatorial technique that permits the selection of binding clones from highly complex protein libraries.  We have used phage display to dissect critical determinants underlying specific protein-protein and protein-antibody interactions. Ultimately, this information can be utilized to design new proteins or antibodies with enhanced function; and contributes generally to our knowledge of protein recognition.  Projects focus on applications in T-cell immunology, chronic lymphocytic leukemia, Alzheimer’s disease, and viral immunotherapy.