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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI034533-21
Application #
8495673
Study Section
Special Emphasis Panel (ZAI1-KP-M (J3))
Project Start
Project End
Budget Start
2013-07-18
Budget End
2014-06-30
Support Year
21
Fiscal Year
2013
Total Cost
$543,530
Indirect Cost
$79,729
Name
University of Rhode Island
Department
Type
DUNS #
144017188
City
Kingston
State
RI
Country
United States
Zip Code
02881
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
Woda, Marcia; Friberg, Heather; Currier, Jeffrey R et al. (2016) Dynamics of Dengue Virus (DENV)-Specific B Cells in the Response to DENV Serotype 1 Infections, Using Flow Cytometry With Labeled Virions. J Infect Dis 214:1001-9
Nisalak, Ananda; Clapham, Hannah E; Kalayanarooj, Siripen et al. (2016) Forty Years of Dengue Surveillance at a Tertiary Pediatric Hospital in Bangkok, Thailand, 1973-2012. Am J Trop Med Hyg 94:1342-7
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

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