Albert Einstein College of Medicine
New York. NY
Structure-guided Design of Immunogens Based on Flavivirus Glycoprotein E Domain III, EDIII
The flaviviruses are globally significant vector-borne viruses that include Dengue virus, serotypes 1-4, DENV1-4, Zika virus, ZIKV, and Powassan virus, POWV. DENV and ZIKV are spread by Aedes aegypti and Aedes albopictus mosquitos, are endemic to subtropical regions, and can cause millions of infections per year. POWV is spread by ticks and is less common, but is associated with a severe and sometimes fatal encephalitis.
We are using phage display and protein engineering to develop novel immunogens based on EDIII from DENV, ZIKV, and POWV. EDIII is an attractive target for vaccine design because it is relatively small, ~80 residues, adopts a well-defined Ig-like fold, and is the target for protective neutralizing antibodies.
We have engineered “resurfaced” EDIIIs from both DENV and ZIKV, whereby non-neutralizing epitopes are masked by mutation. Furthermore, we have developed protein nanoparticles containing EDIIIs from DENV, ZIKV, and POWV using spycatcher conjugation technology. We will describe these design strategies and their potential for development of novel subunit vaccines.