Dengue virus (DENV) infections of humans has steadily increased in importance as an emerging infectious disease, and the development of protective vaccines to DENV disease has been impeded by a lack of understanding of the specificity of virus-specific immune responses and their role in protection and disease. To address these critical issues related to DENV infection and disease, we have established a unique collaborative research consortium, US-Brazil Center for Immunology of Emerging Infectious Diseases (CIEID) that includes investigators from the University of Pittsburgh, Johns Hopkins School of Medicine, and the Laboratory of Virology and Experimental Therapy in Recife, Brazil. The focus of the CIEID is to conduct a comprehensive analysis of the immune responses to DENV infection of humans using the unique clinical samples obtained from the Clinical Core in Brazil to characterize the initial role of antigen presenting cells in DENV immunopathogenesis (Project 1), to define the interaction of T-lymphocyte with dendritic cells in the progression of immunity and disease (Project 2), to define how DENV suppresses innate immune responses to DENV infection (Project 3), and to define the specificity of common T-lymphocyte responses that are established to DENV infection. These translational immunology studies are complemented by a Technology Development Project designed to identify reliable biomarkers of DENV disease (Project 5), by a Pilot Projects Core to recruit new research areas and expertise, by a Virology Core to provide viral and molecular reagents, and by an Adminstrative Core to coordinate project activities and interactions with the CCHI Network Steering Committee. It is anticipated that the results of the proposed studies will produce important new insights into the role of DENV-specific immunity in infection and disease that can then inform strategies for treatment and vaccine development. In addition, it is expected that the US-Brazil CIEID will provide platform technologies and comprehensive expertise in translational immunology that can readily be applied to other emerging infections diseases or biodefense pathogens.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-KS-I (J4))
Program Officer
Cassetti, Cristina
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
Public Health & Prev Medicine
Schools of Public Health
United States
Zip Code
Santos, Jefferson J S; Cordeiro, Marli T; Bertani, Giovani R et al. (2014) A two-plasmid strategy for engineering a dengue virus type 3 infectious clone from primary Brazilian isolate. An Acad Bras Cienc 86:1749-59
Piazza, P; Campbell, D; Marques, E et al. (2014) Dengue virus-infected human dendritic cells reveal hierarchies of naturally expressed novel NS3 CD8 T cell epitopes. Clin Exp Immunol 177:696-702
Santos, Jefferson J S; Cordeiro, Marli T; Bertani, Giovani R et al. (2014) A two-plasmid strategy for engineering a dengue virus type 3 infectious clone from primary Brazilian isolate. An Acad Bras Cienc 0:0
Comber, Joseph D; Karabudak, Aykan; Huang, Xiaofang et al. (2014) Dengue virus specific dual HLA binding T cell epitopes induce CD8+ T cell responses in seropositive individuals. Hum Vaccin Immunother 10:3531-43
Garcia-Bates, Tatiana M; Cordeiro, Marli T; Nascimento, Eduardo J M et al. (2013) Association between magnitude of the virus-specific plasmablast response and disease severity in dengue patients. J Immunol 190:80-7
Castanha, P M S; Cordeiro, M T; Martelli, C M T et al. (2013) Force of infection of dengue serotypes in a population-based study in the northeast of Brazil. Epidemiol Infect 141:1080-8