Bioinformatics Approach to Influenza A/H1N1 Vaccine Immune Profiling

申请资料(申请人提供)：本申请旨在资助一项研究，利用系统生物学及生物信息学方法，研究人类在接种甲型/加州/甲型H1N1流感季节性疫苗前后的免疫反应。我们将使用系统生物学的方法开发新的全面的免疫配置文件，以定义特定的免疫配置文件，以区分免疫后老年人的基线、早期、中期和晚期(稳态)先天、体液和细胞免疫反应。我们的广泛目标是创建全面和创新的免疫概况，解释和预测对甲型H1N1流感疫苗免疫反应的变化。使用新的生物信息学方法和一套全面的分析方法(免疫结果、免疫图谱和免疫衰老标记物)，我们将在免疫衰老前和衰老后的受试者中创建免疫图谱的模型，这是这一应用的重点。为了实现这些目标，我们提出了以下具体目标：1)描述和表征甲型H1N1流感疫苗接种前后(第0天到第75天)的纵向免疫系统概况，2)在疫苗接种后第0天到第75天在体液和细胞水平上识别与疫苗免疫原性相关的免疫概况，以及3)在新的复制队列中复制和验证在特定目标1-2中发现的免疫概况和模型。这项提议具有创新性和重大意义，因为它将：利用以前没有被应用于了解甲型流感疫苗诱导的免疫反应的尖端技术。创建全面的免疫配置文件，提供一个模型和框架，描述和解释从抗原攻击后的基线、早期、中期(峰值)和晚期(稳态)免疫反应到甲型流感疫苗的连续免疫反应的变异性。提供对开发新的流感疫苗很重要的常识。这一系列AIMS的最终结果将是第一个使用新的高维技术和生物信息学方法的甲型流感疫苗特异性免疫原性的系统免疫图谱和模型，并有可能为理解复杂生物系统的分析方法设定标准。与公共卫生相关：这笔赠款将提供新的信息，描述如何产生对灭活甲型H1N1流感疫苗的免疫反应。这些信息有助于设计新的疫苗来控制这种致命的病毒性疾病。

DESCRIPTION (provided by applicant): This application is for funding of a study to characterize the human immune response before and after 2010-2011 influenza A/California/H1N1 seasonal vaccination by developing comprehensive immune profiles utilizing systems biology and bioinformatics approaches. We will develop novel comprehensive immune profiles using a systems biology approach to define specific immune profiles that discriminate baseline, early, mid, and late (homeostatic) innate, humoral, and cellular immune responses after immunization among older adults. Our broad objective is to create comprehensive and innovative immune profiles that explain and predict variations in immune responses to influenza A/H1N1 vaccines. Using novel bioinformatic approaches and a comprehensive assay set (immune outcomes, immune profiles, and immunosenescence markers), we v\/ill create models of immune profiling that are the focus of this application, among pre- and postimmunosenescent subjects. To accomplish these goals, we propose the following specific aims: 1) To describe and characterize longitudinal immune system profiles (Day 0 to Day 75) before and after influenza A/H1N1 vaccination, 2) To identify immune profiles that correlate with vaccine immunogenicity at the humoral and cellular levels Day 0 to Day 75 after vaccination, and 3) To replicate and verify the immune profiles and models discovered in Specific Aims 1-2 in a new replication cohort. This proposal is innovative and significant in that it will: Utilize cutting edge technology that has not previously been applied to understanding influenza A vaccine-induced immune responses. Create comprehensive immune profiles that provide a model and a framework that describe and explain the variability of immune responses to influenza A vaccine in the continuum from baseline, early, mid (peak), and late (homeostatic) immune responses after antigenic challenge. Provide general knowledge important to the development of new influenza vaccines. The end result of this series of aims will be the first systematic immune profiles and models of influenza A vaccine-specific immunogenicity using novel high dimensional technology and bioinformatics approaches, and has the potential to set the standard for analytical methods to understand complex biologic systems. Relevance to Public Health: This grant will provide novel information describing how immune responses to inactivated influenza A/H1N1 vaccine are generated. This information is useful in designing new vaccines to control this deadly viral disease.