Proteomic Profiling for Influenza Vaccination/Infection

流感疫苗/感染的蛋白质组学分析

• 批准号: 7060077
• 负责人: RICHARD R. DRAKE
• 金额: $ 27.5万
• 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 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7060077
• 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，在新的/未知病原体发作的生物恐怖攻击时，传染剂的早期检测和诊断对于治疗和危机管理至关重要。同样，生物固定的准备也需要鉴定与病原体感染有关的新蛋白质和宿主细胞对感染的反应。基于质谱的蛋白质组学方法的最新进展可以应用于实现这些目标，并且是该提案的主要重点。一支强大的转化研究和临床团队已经组装，以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，包括流感疫苗平台以及存档的感染血清样品。我们的中心假设是，可以通过血清（或其他临床液）的蛋白质组学分析来量化对疫苗接种的免疫反应，并且对不同传染剂的宿主反应是独特的，可以通过蛋白质组学“指纹”。我们建议使用甲型生物恐怖病原体流感病毒作为模型剂，以开发SELDI质谱法蛋白质组学分析系统来监测疫苗反应和早期检测/诊断感染。我们研究的最终目的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中流感的发病率和死亡率。将采用两种实验方法。一种是使用从年轻和老年患者同类中获得的流感前和流感疫苗疫苗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，类似的年轻成人队列将接收鼻内炎症疫苗。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。第二种方法将比较患有对照和RSV感染患者的急性感染流感患者的血清和鼻拭子的蛋白质组学特征。在所有分析样品中鉴定出的潜在生物标志物蛋白将通过质谱分离并测序。这些研究可能导致发展至关重要的新范式，以提高我们针对病毒病原体的国家生物污染物准备所需的检测，诊断和疫苗接种策略。