Systems Biology Approach to Analysis of Vaccine Response in Healthy Individuals

疫苗代表了免疫学的重大成功，使无数人免于患上 感染。尽管它们取得了成功，但我们对疫苗如何有效地刺激保护作用知之甚少。 免疫反应。疫苗可分为三类：一)高效疫苗，如 黄热病、麻疹和天花；二)在大多数人中产生保护性免疫的良好疫苗 包括季节性流感(流感)疫苗、乙肝和肺炎；以及三)疫苗 目前没有效果，包括艾滋病、疟疾和丙型肝炎。我们推测 了解好的疫苗在健康人中的运作方式并了解其缺点 通过对低反应性人群的研究，我们可以揭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种理解：i)认识到 树突状细胞在诱导和调节免疫应答中的作用及II)高通量分子研究进展 系统生物学方法背后的剖析技术。我们假设一个系统生物学 分析将对与流感有效反应相关的免疫变化产生全面的看法 接种疫苗。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，提出了四个目标： 目的1：建立健康受试者的基线免疫图谱。 目的2：建立健康人群接种流感疫苗的免疫图谱。 目的：鉴定S DC亚群对流感疫苗免疫应答的分子特征。 目的4：鉴定流感疫苗免疫后激活的单核细胞的分子特征。

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.