The long-term objective of this project is to define the immunological mechanisms that determine the outcome of dengue virus (DV) infection. A large body of information supports the model of immunopathogenesis of severe dengue disease; however, open questions remain about the principal determinants of disease. DV interaction with host innate and adaptive immunity responses is highly complex, and can result in the production of pro-inflammatory, antiinflammatory, and/or vasoactive cytokines. This Project seeks to understand the contribution of individual components of the immune response to different clinical disease manifestations. These findings will be important for vaccine development, by identifying the key immunologic correlates of vaccine-induced protection as opposed to immunopathology on subsequent exposure to DV.
The Specific Aims of this Project are: 1. to define the viral and innate host determinants of the cellular response to DV infection, by determining the dendritic cell (DC) cytokine response to DV strains associated with different disease severity and the association of DC responses with host genotypes; 2. to define the immunological mechanisms contributing to clinical disease in acute DV infection, by determining the kinetics of activation and expansion of DV-specific B cells and T cells; 3. to define immunological correlates of the response to tetravalent DV immunization, by determining the associations between pre-existing DV-specific immunity and the response to vaccination and between the vaccine-induced DV-specific immunity and clinical outcome (adverse events, protection, and breakthrough DV infections).
Dengue is an important tropical mosquito-borne viral disease that causes shock as a result of the body's immune response. We will study how different parts of the host immune system react to infection with dengue virus to understand how virus infection causes disease. This research will help guide the development of vaccines and new treatments for dengue.
| Salje, Henrik; Cummings, Derek A T; Rodriguez-Barraquer, Isabel et al. (2018) Reconstruction of antibody dynamics and infection histories to evaluate dengue risk. Nature 557:719-723 |
| Park, Sangshin; Srikiatkhachorn, Anon; Kalayanarooj, Siripen et al. (2018) Use of structural equation models to predict dengue illness phenotype. PLoS Negl Trop Dis 12:e0006799 |
| Kang, Jeon-Young; Aldstadt, Jared (2017) The Influence of Spatial Configuration of Residential Area and Vector Populations on Dengue Incidence Patterns in an Individual-Level Transmission Model. Int J Environ Res Public Health 14: |
| Srikiatkhachorn, Anon; Mathew, Anuja; Rothman, Alan L (2017) Immune-mediated cytokine storm and its role in severe dengue. Semin Immunopathol 39:563-574 |
| Rattanamahaphoom, Jittraporn; Leaungwutiwong, Pornsawan; Limkittikul, Kriengsak et al. (2017) Activation of dengue virus-specific T cells modulates vascular endothelial growth factor receptor 2 expression. Asian Pac J Allergy Immunol 35:171-178 |
| Kalayanarooj, Siripen; Rothman, Alan L; Srikiatkhachorn, Anon (2017) Case Management of Dengue: Lessons Learned. J Infect Dis 215:S79-S88 |
| Moulton, Steven L; Mulligan, Jane; Srikiatkhachorn, Anon et al. (2016) State-of-the-art monitoring in treatment of dengue shock syndrome: a case series. J Med Case Rep 10:233 |
| Srikiatkhachorn, Anon; Yoon, In-Kyu (2016) Immune correlates for dengue vaccine development. Expert Rev Vaccines 15:455-65 |
| Rothman, Alan L; Ennis, Francis A (2016) Dengue Vaccine: The Need, the Challenges, and Progress. J Infect Dis 214:825-7 |
| Townsley, E; O'Connor, G; Cosgrove, C et al. (2016) Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells. Clin Exp Immunol 183:419-30 |
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