Bioinformatics Approach to Influenza A/H1N1 Vaccine Immune Profiling

描述（由申请人提供）：本申请旨在资助一项研究，通过利用系统生物学和生物信息学方法开发全面的免疫特征，表征2010-2011年甲型/加州/H1N1流感季节性疫苗接种前后的人体免疫应答。我们将使用系统生物学方法开发新的综合免疫谱，以定义特定的免疫谱，区分老年人免疫后的基线，早期，中期和晚期（稳态）先天，体液和细胞免疫应答。我们的广泛目标是建立全面和创新的免疫谱，解释和预测对甲型H1N1流感疫苗的免疫反应的变化。使用新的生物信息学方法和全面的测定集（免疫结果、免疫概况和免疫衰老标记物），我们将在免疫衰老前和免疫衰老后受试者中创建免疫概况模型，这是本申请的重点。为实现这些目标，我们提出以下具体目标：1）描述和表征纵向免疫系统概况（第0天至第75天）接种A/H1N1流感疫苗之前和之后，2）为了鉴定在接种疫苗后第0天至第75天在体液和细胞水平上与疫苗免疫原性相关的免疫特征，和3）在新的复制组群中复制和验证在特异性目的1-2中发现的免疫谱和模型。该提案具有创新性和重要性，因为它将：利用以前未应用于了解甲型流感疫苗诱导的免疫反应的尖端技术。创建全面的免疫特征，提供模型和框架，描述和解释抗原激发后从基线、早期、中期（峰值）和晚期（稳态）免疫应答的连续体中对甲型流感疫苗的免疫应答的变异性。提供对开发新流感疫苗重要的一般知识。这一系列目标的最终结果将是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第一个系统性免疫特征和模型，并有可能为理解复杂生物系统的分析方法设定标准。与公共卫生的相关性：这项资助将提供新的信息，描述灭活甲型H1N1流感疫苗如何产生免疫反应。这些信息对于设计新疫苗来控制这种致命的病毒性疾病非常有用。

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.