Dengue Human Immunology Project Consortium (DHIPC)

The overall goal of this HIPC is to appraise the diversity and commonality of the human immune response to dengue virus infection or vaccination using a high-throughput systems biology approach together with detailed clinical outcomes in at-risk human cohorts. Dengue virus is a mosquito-borne flavivirus that affects about 100 million people each year. Sequential infection with any of the four different dengue virus serotypes is common, and this is associated with partial and transient protection against the other three strains as well as an increased risk of developing a severe form of the disease. There is no drug treatment for dengue virus infection, and the recently tested tetravalent vaccine provided limited protection against the dengue 2 virus serotype. We propose to leverage recent advances in human immune profiling methods to characterize the diverse states of the human innate immune system after dengue virus infection and before and after vaccination against this infectious disease. The Genomics Core will serve as a centralized resource with high-throughput assays and expertise necessary to derive human immune profiles or signatures for disease severity (Project 1), vaccine responsiveness (Project 2), or infection (Project 3). The Genomics Core will be responsible for state-of-the-art DNA sequencing, direct multiplexed measurement of gene expression, and genotyping platforms along with a dedicated pipeline for managing, analyzing and sharing these large sequence datasets.