The long-term objective of this project is to elucidate the relationships among dengue virus (DENV)-specific immune responses measured before and during acute infection, DENV-specific immune responses induced by a tetravalent live-attenuated vaccine, and the clinical outcome of infection. The adaptive immune response to DENV has the potential for either positive (protective) or negative (pathologic) effects on subsequent DENV infection. We hypothesize that quantitative, qualitative, and kinetic aspects of DENVspecific immune responses all play important roles in determining the outcome of infection, and that these features of DENV-specific immunity depend on the sequence and frequency of exposure to DENV. We will address our hypotheses through the following Specific Aims: 1. Define immunodominant T cell epitopes associated with secondary DENV infection and specific HLA alleles and sequences of infection 2. Define the relationships between pre-infection DENV-specific immune responses, immune activation during infection, and clinical outcome 3. Define the relationships between pre-existing DENV-specific immune responses, immune responses to vaccination with Chimerivax-DEN (tetravalent DENV-YFV chimeric vaccine), and vaccine efficacy Identifying the features of protective and pathological immunity to DENV is of importance to advancing vaccine development and utilization.
The immune response to dengue virus can be either beneficial (protect from infection and/or illness) or harmful (increased risk for severe disease). This project will analyze immune responses to dengue virus in individuals with natural exposure and in participants in a vaccine trial in order to understand how the immune response relates to the outcome of infection with dengue virus.
| 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 |
| 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 |
| 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 |
Showing the most recent 10 out of 119 publications
