Proteomic Profiling for Influenza Vaccination/Infection

流感疫苗/感染的蛋白质组学分析

• 批准号: 6867063
• 负责人: RICHARD R. DRAKE
• 金额: $ 28.16万
• 依托单位: EASTERN VIRGINIA MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6867063
• 关键词: Orthomyxoviridae; active immunization; biomarker; biotechnology; bioterrorism /chemical warfare; cellular immunity; clinical research; communicable disease diagnosis; early diagnosis; electrospray ionization mass spectrometry; host organism interaction; human old age (65+); human subject; humoral immunity; immune response; influenza; influenza vaccines; leukocyte activation /transformation; longitudinal human study; matrix assisted laser desorption ionization; proteomics; surface enhanced laser desorption ionization; technology /technique development; vaccine evaluation; young adult human (21-34)

DESCRIPTION (provided by applicant): Quantitative and qualitative analysis of immune response to vaccination is a critical component for testing new vaccines in preparation for a bioterrorist attack. In addition, early detection and diagnosis of an infectious agent is crucial for treatment and crisis management in the event of a bioterrorist attack by a new/unknown pathogen. Similarly, identification of new proteins involved in pathogen infection and host-cell responses to infection are also needed for biodefense preparedness. Recent advances in mass spectrometry-based proteomic methods can be applied to achieve these goals, and is a major focus of this proposal. A strong translational research and clinical team has been assembled to combine new proteomic and bioinformatics tools with existing immunological assays, both influenza vaccine platforms, and archived infected serum samples. Our central hypothesis is that immune responses to vaccination can be quantified by proteomic profiling of serum (or other clinical fluids), and that the host response to different infectious agents are unique and can be 'fingerprinted' by proteomics. We propose to use influenza virus, a Category C bioterrorism pathogen, as a model agent to develop a SELDI mass spectrometry proteomic profiling system for monitoring vaccine response and early detection/diagnosis of infection. The ultimate goal of our study is to reduce the morbidity and mortality of influenza from natural and potential bioterrorism infections by improving vaccine efficacy and early diagnosis. Two experimental approaches will be taken. One is to use proteomic profiling of pre- and post influenza vaccination serum obtained from young and elderly patient cohorts to identify surrogate biomarkers reflective of the immune response. For comparison, a similar young adult cohort will receive the live-virus intranasal FluMist vaccine. These protein profile differences will be correlated with T cell activation and antibody responses to vaccination. The second approach will compare proteomic profiles from serum and nasal swabs of acutely infected influenza patients with control and RSV-infected patients. Potential biomarker proteins identified in all analyzed samples will be isolated and sequenced by mass spectrometry. These studies could lead to the development of crucial new paradigms for detection, diagnosis and vaccination strategies necessary to increase our national biodefense preparedness against viral pathogens.

描述（由申请人提供）：对疫苗接种免疫反应的定量和定性分析是测试新疫苗以准备生物恐怖袭击的关键组成部分。此外，在发生新/未知病原体的生物恐怖袭击时，传染原的早期检测和诊断对于治疗和危机管理至关重要。同样，生物防御准备工作也需要鉴定参与病原体感染和宿主细胞对感染反应的新蛋白质。基于质谱的蛋白质组学方法的最新进展可用于实现这些目标，并且是该提案的主要焦点。已经组建了一支强大的转化研究和临床团队，将新的蛋白质组学和生物信息学工具与现有的免疫学测定、流感疫苗平台和存档的感染血清样本相结合。我们的中心假设是，对疫苗接种的免疫反应可以通过血清（或其他临床液体）的蛋白质组学分析来量化，并且宿主对不同传染源的反应是独特的，可以通过蛋白质组学进行“指纹识别”。我们建议使用流感病毒（一种 C 类生物恐怖主义病原体）作为模型剂来开发 SELDI 质谱蛋白质组分析系统，用于监测疫苗反应和感染的早期检测/诊断。我们研究的最终目标是通过提高疫苗功效和早期诊断来降低自然和潜在生物恐怖感染引起的流感的发病率和死亡率。将采取两种实验方法。一种是利用从年轻和老年患者群体获得的流感疫苗接种前后血清的蛋白质组学分析来鉴定反映免疫反应的替代生物标志物。为了进行比较，类似的年轻人队列将接受活病毒鼻内 FluMist 疫苗。这些蛋白质谱差异将与 T 细胞激活和抗体对疫苗接种的反应相关。第二种方法将比较急性感染流感患者与对照和 RSV 感染患者的血清和鼻拭子的蛋白质组谱。所有分析样品中鉴定出的潜在生物标志物蛋白质将被分离并通过质谱法进行测序。这些研究可能会导致开发重要的检测、诊断和疫苗接种策略新范例，以增强我们国家针对病毒病原体的生物防御准备。