Immune Response to High-Dose vs. Standard Dose Influenza Vaccine

高剂量与标准剂量流感疫苗的免疫应答 临床医生目前没有方法来预测老年人的流感疫苗反应 容易获得且相对便宜。这项研究的长期目标是确定 T细胞反应是流感严重并发症的替代物（生物标志物）， 可以用来预测疫苗的有效性。这种松散的生物标志物将提供 临床医生有能力决定谁可能受益于更新或更多的反应原性疫苗， 例如较高抗原剂量疫苗，或在流感期间可能需要化学预防的患者 由于疫苗接种反应不充分。 这项为期5年的提案是一项高剂量裂解病毒流感疫苗（SVV）的随机研究， (HD)与标准剂量（SD）制剂相比，在五个流感季节中的每一个季节中， 疫苗介导的抗流感保护的决定因素以及这些免疫 接种新批准的高剂量流感疫苗可以增强介体 在年老体弱的受试者中。这项研究将使我们能够实现以下目标： 目的一：确定新上市的高剂量疫苗是否优于 标准剂量的IFN-γ：IL-10比率和GrzB水平的保护性增加。我们 假设是，IFN：IL-10比值高于阈值水平的受试者比例 （>10）和/或GrzB（>990 U/mg蛋白质）在接种疫苗后， 接受高剂量SVV与标准剂量SVV。 目的II：评价在2008年至2009年期间， 静息T细胞（bGrzB）。脆弱代表一种经过验证的、可衡量的增强状态， 老年人的脆弱性。我们的假设是，日益脆弱将是积极的， 与较高的bGrzB水平有关。 目的III：建立疫苗介导的保护作用的预测因子， 即时检测我们的假设是，虚弱程度的增加，CMV血清阳性 状态和bGrzB活性与较低的细胞溶解活性、减少的Th 1：Th 2 对流感挑战的反应，以及流感疾病的风险增加。

Immune Response to High-Dose vs. Standard Dose Influenza Vaccine Clinicians currently do not have methods to predict influenza vaccine responses in older adults that are accessible and relatively inexpensive. The long-term goal of this research is to identify the T-cell responses that are surrogates (biomarkers) of serious complications of influenza and can be used to predict vaccine effectiveness. Such loosely termed biomarkers would provide clinicians with the ability to decide who might benefit from newer or more reactogenic vaccines, such as a higher antigen dose vaccine, or who might require chemoprophylaxis during influenza season due to inadequate response to vaccination. This 5-year proposal is a randomized study of split-virus influenza vaccine (SVV) in a high-dose (HD) vs. standard dose (SD) formulation in each of five influenza seasons to define the key determinants of vaccine-mediated protection against influenza and how these immunologic mediators may be enhanced by vaccination with a newly approved high-dose influenza vaccine in frail older subjects. This study will allow us to address the following aims: AIM I: Determine whether a newly marketed high dose vaccine performs better than standard doses in achieving protective increases in IFN¿:IL-10 ratios and GrzB levels. Our hypothesis is that the proportion of subjects above the threshold level for the IFN¿:IL-10 ratio (>10) and/or GrzB (>990 U/mg protein) following vaccination will be significantly higher in those receiving the high-dose SVV vs. standard-dose SVV. AIM II: Evaluate the association of degree of frailty to CMV status and GrzB levels in resting T cells (bGrzB). Frailty represents a validated and measurable state of enhanced vulnerability in older individuals. Our hypothesis is that increasing frailty will be positively associated with higher bGrzB levels. AIM III: Establish predictors of vaccine-mediated protection that can be developed for point-of-care testing. Our hypothesis is that increased levels of frailty, CMV seropositive status, and bGrzB activity are associated with lower cytolytic activity, diminished Th1:Th2 responses to influenza challenge, and an enhanced risk of an influenza illness.