Sculpting the immunological response to dengue fever by polytopic vaccination

The twin challenges of immunodominance and heterologous immunity have hampered discovery of an effective vaccine against all four dengue viruses. Here, we explore how the T cell competition and selection underlying these asymmetrical properties impede effective T cell vaccine design. The theory we develop predicts dengue vaccine clinical trial data well. From the insights that we gain by this theory, we propose two new ideas for design of epitope-based T cell vaccines against dengue: polytopic injection and subdominant epitope priming.