Project 2 - Immune profiling of candidate vaccines for dengue

项目 2 - 登革热候选疫苗的免疫分析

• 批准号: 10153664
• 负责人: Jorge E Osorio
• 金额: $ 30万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10153664
• 关键词: Address; Animal Model; Antibody Response; Antibody Specificity; Antibody titer measurement; Attenuated; Biological Assay; Blood specimen; CD8-Positive T-Lymphocytes; Candidate Disease Gene; Cells; Clinical; Communicable Diseases; Dengue; Dengue Infection; Dengue Vaccine; Development; Disease; E protein; Exposure to; Fever; Flavivirus; Gene Expression Profile; Gene Expression Profiling; Gene Proteins; Genome; Goals; Hemorrhagic Shock; Host Defense; Human; Immune; Immune response; Immune system; Immunity; Immunization; Immunology; Individual; Infection; Innate Immune Response; Investigation; Laboratories; Longevity; Measurement; Modeling; Molecular; Pathogenesis; Pathology; Pathway interactions; Phase II Clinical Trials; Play; Proteins; Proteomics; RNA; Risk Factors; Role; Sampling; Serotyping; Serum; Shapes; Stains; Systems Biology; T cell response; Testing; Vaccination; Vaccines; Vertebral column; Viral Hemorrhagic Fevers; Viremia; Virus; Virus Diseases; Whole Blood; adaptive immune response; adaptive immunity; arthropod-borne; chemokine; cross reactivity; cytokine; genome-wide; human disease; immunogenic; immunogenicity; insight; interest; neutralizing antibody; phase I trial; predictive marker; response; transcriptome; vaccine access; vaccine candidate; vaccine development; virology

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).

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毒株（TDV-2）和三种嵌合病毒组成 含有在DENV-1、DENV-3和DENV-4的背景下表达的prM和E蛋白基因， 减毒TDV-2基因组骨架（分别为TDV-1、TDV-3和TDV-4）。更好的 对TDV疫苗受体的天然免疫应答如何形成适应性的理解 免疫力对研制安全有效的疫苗至关重要。在项目2中， 登革热人类免疫学项目联盟（DHIPC）采用系统生物学方法 剖析先天性和适应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TDV接种后，这将与四价中和抗体的测量相关。 抗体滴度和/或T细胞应答的大小和多功能性。这应该 能够鉴定预测疫苗免疫原性和效力的标志物。先天 在项目2中获得的免疫特征将与平行获得的免疫特征进行比较 来自天然人DENV感染（项目1）和离体感染的样品的研究 相关的初级免疫细胞与相同的病毒，以获得机制的见解（项目3）。