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

大剂量与标准剂量流感疫苗的免疫应答 临床医生目前还没有方法预测老年人对流感疫苗的反应 交通便利，价格相对便宜。这项研究的长期目标是确定 作为流感严重并发症的替代物(生物标记物)的T细胞反应 可以用来预测疫苗的有效性。这种宽泛的生物标记物将提供 临床医生有能力决定谁可能从新的或更多的反应性疫苗中受益， 例如更高抗原剂量的疫苗，或在流感期间可能需要化学预防的人 由于对疫苗接种的反应不充分，这是一个季节。 这项为期5年的建议是一项大剂量分离病毒流感疫苗(SVV)的随机研究 (HD)与标准剂量(SD)在五个流感季节的每一年的配方对比，以确定关键 疫苗介导的流感保护的决定因素以及这些免疫学 可以通过接种新批准的大剂量流感疫苗来增强介体 在虚弱的老年受试者中。这项研究将使我们能够实现以下目标： 目标一：确定新上市的大剂量疫苗是否比 达到保护性增加干扰素：IL-10比率和GrzB水平的标准剂量。我们的 假设是超过干扰素：IL-10比率阈值水平的受试者比例 (&gt；10)和/或GrzB(&gt；990U/mg蛋白质) 接受高剂量SVV与标准剂量SVV。 目的II：评估脆弱程度与CMV状态和GrzB水平的关系 静息T细胞(BGrzB)。脆弱性代表经过验证且可衡量的增强状态 老年人的脆弱性。我们的假设是，不断增加的脆弱性将是积极的 与较高的bGrzB水平相关。 目标三：建立疫苗介导的保护的预测因子，可以开发用于 护理点测试。我们的假设是，虚弱程度的增加，CMV血清阳性 状态和bGrzB活性与细胞溶解活性降低、Th1：Th2减弱相关 对流感挑战的反应，以及流感疾病风险的增加。

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.