Immune responses defining efficiency of influenza vaccination

我们物种的遗传变异决定了一些个体会发展出强烈的体液和细胞 对疫苗的免疫反应，而其他人则不是。随着年龄的增长，保护性免疫的这些差异 变得更加严重，反映在老年人因感染而死亡和发病的风险增加 个人。例如，季节性流感的影响在老年年龄组中尤为严重， 每年死于流感的2万至4万人中，90%发生在年龄段以上的个人 65岁。然而，三价灭活流感疫苗的效力低至30%，脆弱的 有更严重残疾、住院、跌倒和死亡风险的老年人的子集代表 一个特别脆弱的群体。这个项目建立在我们招募和评估流感的经验基础上 年轻人和老年人的疫苗反应，以及我们获得独特队列的机会--例如虚弱的老年人 个人(包括招募的860名养老院老年人参加由NIH资助的 肺炎预防)和一组300名30岁以下的人已经在全基因组范围内 基因分型。我们将利用多维流式细胞术和定量基因表达 核心，以及项目3的分析方法，以开发一个细胞和基因表达签名 成功接种流感疫苗的先天和获得性免疫反应，并将阐明 队列中这些特征的衰老和功能状态受损(如老年虚弱综合征) 指年轻、非虚弱的老年人和虚弱的老年人。我们对300个基因分型的遗传信息的获取 接受流感疫苗接种的个人也将促进细胞和基因表达数据的整合 与疫苗反应的遗传相关。鉴定人类的基因及其等位基因变异 强健或弱小的反应以及它们的表达模式如何受到年龄或脆弱的影响是一个 有必要更好地了解我们的免疫系统的功能。此外，理解 免疫反应的遗传结构可能识别可能成为靶点的免疫途径 根据需要加强或抑制免疫反应的疗法、药物或其他生物疗法。

The genetic variability of our species dictates that some individuals will develop strong humoral and cellular immune responses to vaccines whereas others do not. With aging, these differences in protective immunity become even more severe, reflected in the increased risk for death and morbidity from infections in older individuals. For example, the impact of seasonal influenza is particularly acute in the geriatric age group, with 90% of the 20 to 40 thousand annual deaths attributed to influenza occurring in individuals over the age of 65. However, the efficacy of the trivalent inactivated influenza vaccine is as low as 30%, and the frail subset of elderty individuals who are at risk for worsened disability, hospitalization, falls and death, represent a particularly vulnerable population. This project builds on our experience recruiting and evaluating influenza vaccine response in young and older individuals, and our access to unique cohorts-such as frail elderly individuals (including a recruited cohort of 860 nursing home elders participating in an NIH-funded trial of pneumonia prevention) and a group of 300 individuals under the age of 30 already subjected to genomewide genotyping. We will utilize the Multidimensional Flow Cytometry and Quantitative Gene Expression Cores, and the analytic methods of Project 3 to develop cellular and gene expression signatures of a successful innate and adaptive immune response to influenza vaccination, and will elucidate the impact of aging and impaired functional status (such as the geriatric syndrome of frailty) on these signatures in cohorts of young, non-frail older, and frail older individuals. Our access to genetic information on 300 genotyped individuals receiving influenza vaccine will also facilitate the integration of cellular and gene expression data with genetic correlates of vaccine response. Identifying the genes and their allelic variations in humans that underlie robust or weak responses, and how their expression patterns are affected by age or frailty is a necessity for a greater understanding of the function of our immune system. Moreover, understanding the genetic architecture of immune responses is likely to identify immune pathways that could be targets of therapies, drugs or other biological treatments to enhance or suppress immune responses as needed.