Takeda Vaccines Inc., is developing a live attenuated tetravalent Dengue vaccine candidate (TDV) that consists of an attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the prM and E protein genes of DENV-1, -3 and -4 expressed in the context of the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4, respectively). A better understanding on how innate immune responses to recipients of TDV vaccine shape adaptive immunity is essential for the development of a safe and effective vaccine. In project 2 of the Dengue Human Immunology Project Consortium (DHIPC) we apply a systems biology approach to dissect the qualitative and quantitative features of the innate and adaptive immune responses generated by TDV. The overall goal of Project 2 is to identify gene expression signatures following TDV vaccination that will be correlated to measurements of tetravalent neutralizing antibody titers and/or the magnitude and multifunctionality of T cell responses. This should enable identifying markers predictive of vaccine immunogenicity and efficacy. The innate immune signatures acquired in Project 2 will be compared to those obtained in parallel investigations of samples from natural human DENV infections (Project 1) and ex vivo infection of relevant primary immune cells with the same viruses to gain mechanistic insight (Project 3).

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI118610-04
Application #
9494382
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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