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).
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