Yeast Ty-Dengue Fusion Particles for Vaccines

Dengue viruses are a leading cause of morbidity and mortality throughout the tropics andsubtropics. It is estimated that more than 100 million people in the tropics are infected annually by thisvirus. This threat has now reached the southern United States with the arrival of the Aedes albopictusmosquito vector. Attempts to develop live attenuated dengue vaccines analogous to the yellow fevervaccine have yet to be successful. The proposal research is directed toward development of a definedsubunit dengue vaccine using yeast virus-like particles (VLPs) fused to peptides of the dengue envelope(E) glycoprotein. Such self-assembling VLPs are comprised of the protein product, p1, of the TYA geneof the yeast transposable element Ty. Fusion of dengue E cDNA fragments to the TYa gene will producep1-dengue fusion proteins. The resulting hybrid VLPs will require a single ultracentrifugation step forpurification and should present epitopes in a highly immunogenic form. During phase I, the feasibility ofthis approach will be tested by constructing a yeast TYA:dengue envelope peptide fusion gene andtesting expression, formation of hybrid VLPs, and immunoreactivity of the hybrid VLPs.