Proteomic Profiling for Influenza Vaccination/Infection

描述（由申请方提供）：疫苗接种免疫应答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，在发生新的/未知病原体的生物恐怖袭击时，感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，鉴定与病原体感染和宿主细胞对感染的反应有关的新蛋白质也是生物防御准备所需要的。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，并且是本提案的主要焦点。一个强大的转化研究和临床团队已经组装到联合收割机结合新的蛋白质组学和生物信息学工具与现有的免疫分析，既流感疫苗平台，和存档的感染血清样本。我们的中心假设是，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，并且宿主对不同感染因子的反应是独特的，可以通过蛋白质组学进行“指纹分析”。我们建议使用流感病毒，C类生物恐怖主义病原体，作为一个模型代理开发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的有效性和早期诊断来降低自然和潜在的生物恐怖主义感染引起的流感的发病率和死亡率。将采取两种实验方法。一种是使用从年轻和老年患者队列获得的流感疫苗接种前和接种后血清的蛋白质组学分析来鉴定反映免疫应答的替代生物标志物。为了进行比较，一个类似的年轻成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细胞活化和对疫苗接种的抗体应答相关。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学谱。将通过质谱法分离和测序在所有分析样本中鉴定的潜在生物标志物蛋白。这些研究可能会导致关键的新模式的检测，诊断和疫苗接种战略的发展，以提高我们的国家对病毒病原体的生物防御准备。

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.