Natural Killer Cell Diversity and Epigenetics in Vaccine Responses

疫苗反应中的自然杀伤细胞多样性和表观遗传学

• 批准号: 9190568
• 负责人: Laura Simpson
• 金额: $ 5.43万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2018-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9190568
• 关键词: Activated Natural Killer Cell; Adenovirus Vector; Antibody Formation; Antigens; Antiviral Agents; Antiviral Response; Attenuated; B-Lymphocytes; Binding Sites; Biological; Biological Assay; Cell Count; Cell Maturation; Cell Separation; Cell physiology; Cells; Chromatin; Clinical; Communicable Diseases; Cytometry; Data; Effector Cell; Enhancers; Epidemic; Epigenetic Process; Foundations; Future; Generations; Genetic Recombination; Goals; HIV; HIV vaccine; Human; Immune; Immune response; Immune system; In Vitro; Infection; Influenza; Influenza vaccination; Interferon Type II; Lead; Life; Measurable; Memory; Methods; Natural Immunity; Natural Increases; Natural Killer Cells; Phase; Phenotype; Play; Predisposition; Production; Research; Role; Sampling; Shapes; Sorting - Cell Movement; Surface; T memory cell; Techniques; Testing; Time; Transposase; Vaccinated; Vaccination; Vaccine Design; Vaccines; Vesicular stomatitis Indiana virus; Viral; Virus; Virus Diseases; Work; abstracting; adaptive immunity; adverse outcome; combinatorial; epigenetic profiling; falls; fight against; genome-wide; global health; human subject; improved; influenza virus vaccine; innovation; insight; new technology; novel; pathogen; promoter; protein expression; receptor; receptor expression; response; transcription factor; vaccination strategy; vaccine response; vaccine trial; vector

Project Summary/Abstract Vaccination is essential to the global fight against infectious diseases. However, some pathogens are experts at evading the immune response, and therefore present a challenge to current vaccination strategies. Influenza vaccination is currently only 60% effective, and depends on proper predictions of influenza strains that will become seasonal epidemics every year. HIV vaccination has been unsuccessful thus far, with some vaccine trials resulting in adverse outcomes. Traditionally, vaccine design focuses on eliciting memory responses by effector cells of the adaptive immune system. However, it is unknown how cells of the innate immune system respond to vaccination, and whether they play a role in successful vaccine responses. Natural killer (NK) cells are effector cells of the innate immune system that respond rapidly to viral infection. In this proposal, we aim to determine the effect of influenza or HIV vaccination on NK cells. We will deeply interrogate the NK cell response to vaccination by using mass cytometry, an innovative new technology that allows the analysis of 40+ protein expression parameters simultaneously at the single cell level. This method will allow us to analyze clinical samples from influenza and HIV vaccine studies in great depth. Additionally, we will determine the cell biological mechanisms involved in generation of a diverse and functional NK repertoire by analyzing the genome-wide epigenetic profiles of NK cells that respond to vaccination and viral infection. This will allow us to define signatures of NK cell maturation, activation, and diversification. These studies will deepen our understanding of the innate immune response to vaccination, which will lay the foundation for future vaccine designs that incorporate both the innate and the adaptive immune systems.

项目摘要/摘要 疫苗接种对于全球抗击传染病至关重要。但是，有些病原体是专家 避免免疫反应，因此对当前的疫苗接种策略提出了挑战。流感 目前，疫苗接种仅有效60％，取决于对流感菌株的适当预测 每年成为季节性流行病。到目前为止，HIV疫苗接种未成功，有一些疫苗 试验导致不良结果。传统上，疫苗设计的重点是通过 自适应免疫系统的效应细胞。但是，尚不清楚先天免疫系统的细胞如何 对疫苗接种的反应，以及它们是否在成功的疫苗反应中发挥作用。天然杀手（NK）细胞 是对病毒感染迅速反应的先天免疫系统的效应细胞。在此提案中，我们的目标是 确定流感或HIV疫苗接种对NK细胞的影响。我们将深入询问NK单元 通过使用质量细胞仪（一种创新的新技术）对疫苗接种的反应，允许分析 在单细胞水平上同时同时进行40+蛋白表达参数。这种方法将使我们能够分析 来自流感和HIV疫苗研究的临床样本深度深入。此外，我们将确定单元格 通过分析来产生多样化和功能性NK曲目的生物学机制 对疫苗接种和病毒感染反应的NK细胞的全基因组表观遗传谱。这将使我们能够 定义NK细胞成熟，激活和多样化的特征。这些研究将加深我们 了解对疫苗接种的先天免疫反应，这将为未来的疫苗奠定基础 设计结合了先天性和自适应免疫系统。