Project 2 - Immune profiling of candidate vaccines for dengue

武田疫苗公司正在开发一种四价登革热减毒活疫苗候选疫苗 (TDV)由减毒的DENV-2株(TDV-2)和三种嵌合病毒组成 包含DENV-1、-3和-4的PrM和E蛋白基因，在 减毒TDV-2基因组骨架(分别为TDV-1、TDV-3和TDV-4)。更好的 对TDV疫苗受者先天免疫反应如何形成适应性的理解 免疫对于开发安全有效的疫苗是至关重要的。在项目2中， 登革热人类免疫学项目联盟(DHIPC)应用系统生物学方法 剖析先天免疫反应和获得性免疫反应的定性和定量特征 由TDV生成。项目2的总体目标是识别基因表达特征 在接种TDV疫苗后，这将与四价中和测量相关 抗体滴度和/或T细胞反应的大小和多功能性。这应该是 能够识别预测疫苗免疫原性和效力的标记。先天的 在项目2中获得的免疫签名将与并行获得的免疫签名进行比较 自然感染和体外感染人DENV样本的调查(项目1) 对具有相同病毒的相关初级免疫细胞进行研究，以获得机理洞察(项目3)。

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).