Immune responses defining efficiency of influenza vaccination

我们物种的遗传变异性决定了一些个体会发展出强大的体液和细胞免疫系统。 免疫反应，而其他人则没有。随着年龄的增长，这些保护性免疫力的差异 这反映在老年人感染死亡和发病的风险增加。 个体例如，季节性流感对老年人的影响特别严重， 每年2万至4万例流感死亡中有90%发生在年龄超过 为65.然而，三价灭活流感疫苗的有效性低至30%，体弱者 有残疾恶化、住院、福尔斯和死亡风险的老年人亚组， 尤其是弱势群体。这个项目建立在我们招募和评估流感的经验之上 年轻人和老年人的疫苗反应，以及我们对独特群体的接触，如体弱的老年人， 个人（包括一个招募的860名养老院老人参加NIH资助的试验， 肺炎预防）和一组300名年龄在30岁以下的人已经接受了全基因组 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，和项目3的分析方法，以开发细胞和基因表达的签名， 成功的先天性和适应性免疫反应的流感疫苗接种，并将阐明的影响， 年龄和受损的功能状态（如老年衰弱综合征）在这些签名的队列 年轻的、不虚弱的老年人和虚弱的老年人。我们获得了300个基因型 接种流感疫苗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性。确定人类的基因及其等位基因变异， 是强或弱反应的基础，以及它们的表达模式如何受到年龄或虚弱的影响， 我们需要更好地了解我们的免疫系统的功能。此外，了解 免疫反应的遗传结构可能会识别出可能成为靶点的免疫途径， 治疗、药物或其他生物治疗以根据需要增强或抑制免疫应答。

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.