Bioinformatics Approach to Influenza A/H1N1 Vaccine Immune Profiling

甲型 H1N1 流感疫苗免疫分析的生物信息学方法

• 批准号: 8695082
• 负责人: Gregory A. Poland
• 金额: $ 508.17万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8695082
• 关键词: Antibodies; Bioinformatics; Biological Assay; California; Complex; Data; Development; Elderly; Funding; Goals; Grant; H1N1 vaccine; Human; Immune; Immune response; Immune system; Immunization; Immunologics; Influenza; Influenza A Virus, H1N1 Subtype; Knowledge; Lead; Marker Vaccines; Marketing; Modeling; Outcome; Poland; Principal Investigator; Production; Public Health; Publishing; ST14 gene; Series; System; Systems Biology; Technology; Time; Vaccination; Vaccines; Variant; Viral Vaccines; Virus Diseases; Work; analytical method; arm; cohort; cost; design; granzyme B; immunogenicity; immunosenescence; influenza virus vaccine; innovation; new technology; novel; novel vaccines; research clinical testing; seasonal influenza; vaccine development; vaccine efficacy; vaccine evaluation

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.

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来描述 2010-2011 年甲型流感/加利福尼亚州/H1N1 季节性疫苗接种前后的人类免疫反应特征。我们将使用系统生物学方法开发新颖的综合免疫谱，以定义特定的免疫谱，以区分老年人免疫后的基线、早期、中期和晚期（稳态）先天、体液和细胞免疫反应。我们的总体目标是创建全面且创新的免疫特征，以解释和预测甲型 H1N1 流感疫苗免疫反应的变化。使用新颖的生物信息学方法和综合测定集（免疫结果、免疫谱和免疫衰老标记物），我们将在免疫衰老前和免疫衰老后受试者中创建免疫谱模型，这是本应用的重点。为了实现这些目标，我们提出以下具体目标：1) 描述和表征甲型 H1N1 流感疫苗接种前后的纵向免疫系统特征（第 0 天至第 75 天），2) 识别与疫苗接种后第 0 天至第 75 天的体液和细胞水平上的疫苗免疫原性相关的免疫特征，以及 3) 复制和验证特定中发现的免疫特征和模型。 新的复制队列中的目标 1-2。该提案具有创新性和重要意义，因为它将： 利用以前未曾应用过的尖端技术来了解甲型流感疫苗诱导的免疫反应。创建全面的免疫特征，提供一个模型和框架，描述和解释抗原攻击后从基线、早期、中期（峰值）和晚期（稳态）免疫反应的连续体中对甲型流感疫苗的免疫反应的变异性。提供对开发新型流感疫苗重要的常识。这一系列目标的最终结果将是使用新型高维技术和生物信息学方法建立甲型流感疫苗特异性免疫原性的第一个系统免疫特征和模型，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。这些信息对于设计控制这种致命病毒性疾病的新疫苗很有用。