Abstract

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).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI118610-01
Application #
8929554
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Patil, Veena S; Madrigal, Ariel; Schmiedel, Benjamin J et al. (2018) Precursors of human CD4+ cytotoxic T lymphocytes identified by single-cell transcriptome analysis. Sci Immunol 3:
Manganaro, Lara; Hong, Patrick; Hernandez, Matthew M et al. (2018) IL-15 regulates susceptibility of CD4+ T cells to HIV infection. Proc Natl Acad Sci U S A 115:E9659-E9667
Andrade, Paulina; Coloma, Josefina; Harris, Eva (2018) ELISPOT-Based ""Multi-Color FluoroSpot"" to Study Type-Specific and Cross-Reactive Responses in Memory B Cells after Dengue and Zika Virus Infections. Methods Mol Biol 1808:151-163
Wang, Daifeng; Liu, Shuang; Warrell, Jonathan et al. (2018) Comprehensive functional genomic resource and integrative model for the human brain. Science 362:
Michlmayr, Daniela; Pak, Theodore R; Rahman, Adeeb H et al. (2018) Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases. Mol Syst Biol 14:e7862
Tsai, Wen-Yang; Youn, Han Ha; Tyson, Jasmine et al. (2018) Use of Urea Wash ELISA to Distinguish Zika and Dengue Virus Infections. Emerg Infect Dis 24:1355-1359
Young, George R; Terry, Sandra N; Manganaro, Lara et al. (2018) HIV-1 Infection of Primary CD4+ T Cells Regulates the Expression of Specific Human Endogenous Retrovirus HERV-K (HML-2) Elements. J Virol 92:
Tan, Yi; Pickett, Brett E; Shrivastava, Susmita et al. (2018) Differing epidemiological dynamics of Chikungunya virus in the Americas during the 2014-2015 epidemic. PLoS Negl Trop Dis 12:e0006670
Lin, Luan; Chen, Quan; Hirsch, Jeanne P et al. (2018) Temporal genetic association and temporal genetic causality methods for dissecting complex networks. Nat Commun 9:3980
Amir, El-Ad David; Guo, Xinzheng V; Mayovska, Oksana et al. (2018) Average Overlap Frequency: A simple metric to evaluate staining quality and community identification in high dimensional mass cytometry experiments. J Immunol Methods 453:20-29

Showing the most recent 10 out of 42 publications