Systems Biology Approach to Analysis of Vaccine Response in Healthy Individuals

疫苗代表了免疫学的重大成功，使无数人免于 感染.尽管疫苗取得了成功，但我们对有效的疫苗如何刺激保护作用知之甚少。 免疫反应。可区分三类疫苗：i）高效疫苗，例如 黄热病、麻疹和天花; ii）可使大多数人产生保护性免疫力的良好疫苗 包括季节性流感（Flu）疫苗、B型肝炎和肺炎疫苗;以及iii）主要 目前还没有效果，包括艾滋病，疟疾和丙型肝炎。我们推测 了解良好疫苗在健康人群中的工作方式，并了解其缺点 通过研究低反应人群，我们可以解开疫苗接种的免疫学原理。 最近的两个事态发展有望产生这样的理解： 树突状细胞在诱导和调节免疫应答中的作用; ii）高通量分子生物学研究进展 剖析系统生物学方法的基础技术。我们假设系统生物学 分析将产生一个全面的看法，免疫改变与流感的有力反应， 预防针我们进一步假设有效的疫苗接种与抗原提呈的早期激活有关， 细胞我们的目标是确定流感疫苗有效抗体反应的早期生物标志物。 为实现这一目标，提出了四项目标： 目的1：建立健康受试者的基线免疫谱。 目的2：建立健康人接种流感疫苗的免疫模式。 目的3：鉴定DC亚群对流感疫苗接种应答的分子特征。 目的4：鉴定活化的单核细胞对流感疫苗应答的分子特征。

Vaccines represent the major success of immunology and have spared countless numbers of people from infections. Despite their success, we understand little about how effective vaccines stimulate protective immune responses. Three classes of vaccine can be distinguished: i) highly effective vaccines such as yellow fever, measles and smallpox; ii) good vaccines which yield protective immunity in a majority of people including seasonal Influenza (Flu) vaccines, hepatitis B and pneumovax; and iii) vaccines which are largely not effective at the current time including HIV-AIDS, malaria, and Hepatitis C. We surmise that understanding the modus operandi of good vaccines in healthy people and understanding their shortcomings by studying hypo-responsive people will permit us to unravel the immunological principles of vaccination. Two recent developments promise to yield such understanding: i) the appreciation of the crucial role of dendritic cells in inducing and tuning the immune responses and ii) advances in high-throughput molecular profiling technologies underlying systems biology approaches. We hypothesize that a systems biology analysis will yield a comprehensive view of the immune alterations associated with a potent response to flu vaccination. We further hypothesize that efficient vaccination is associated to the early activation of antigenpresenting cells. Our goal is to identify early biomarkers of effective antibody responses to flu vaccination. Four aims are proposed to meet this goal: Aim 1: To establish the baseline immune profiles in healthy subjects. Aim 2: To establish the immune profiles of Flu vaccination in healthy subjects. Aim 3: To identify the molecular signatures of DC subset(s) in response to Flu vaccination. Aim 4: To identify the molecular signatures of activated monocytes in response to Flu vaccination.