Secondary dengue viral (DENV) infection of an individual by a different DENV serotype from the firstinfection often results in a more severe disease than primary infection. This is partly due to antibody-dependent enhancement phenomenon (ADE). To date, all dengue vaccine candidates under developmenthave focused on inducing neutralizing antibodies. All used in vitro neutralizing test as a biomarker forprotective immunity and animal model to demonstrate protection against primary DENV infection. We andothers have demonstrated that T cell immunity play an important role in protection against symptomatic andsevere dengue. The T cell epitopes are lacking in most dengue vaccine candidates and the recently licenseddengue vaccine (Dengvaxia® or CYD-TDV), which has age limitation to 9-45 year-old due to ADE in youngchildren. We propose here a new concept of dengue vaccine development. We believe that the moreefficient dengue vaccine should contain both B (Envelop protein) and T cell antigens (Non-structuralproteins). The better animal model for prediction of vaccine efficacy should demonstrate its protectionagainst the effect of ADE, not only primary infection. In addition, recent evidence suggested that ADE couldcreate problem for Zika vaccine. In this proposal, we aim at obtaining a proof of concept that Dengue & Zikavaccine containing the T cell epitopes could prevent antibody-dependent enhancement (ADE) using a mousemodel. We will develop a mouse model for ADE to recapitulate many aspects of human dengue disease,including vascular leakage, elevated serum cytokine levels and reduced platelet count in DENV infection.The products from this project are DENV and ZIKV T cell epitopes ready to use with multiple technologyknown to stimulate T cells and any dengue vaccine candidates, which based on virus envelop (E) antigens.In addition, with the new delivery system technology (nanoparticle) used in this project, it is possible to createa single component penta-valent dengue & Zika vaccine (4DZVx) that could protect against the four dengueserotypes and ZIKV infection. A single component vaccine is likely to overcome the problem of imbalancedimmunity against all four DENV serotypes of the tetravalent dengue vaccines.