Vaccine Induced Immune-Inflammatory Response and Cardiovascular Risk

项目摘要 在来自零星病毒实体的新威胁中，常年流感病毒株继续 造成相当大的发病率和死亡率负担，使人口的年度总风险增加到 大号的。上一季(2018-19年)，流感影响了3550万人，导致49.06万人住院，3.42万人住院 美国的死亡人数每年都在稳步上升。患有心血管疾病的个体 疾病特别容易受到与社区获得性病毒相关的发病率和死亡率的影响 流感等传染病。接种疫苗可显著降低老年人心血管事件的发生率。 在人群一级；然而，在个人一级接种流感疫苗的管理是极不稳定的。 关于(I)体液抗体应答的程度，以及(Ii)心脏保护的程度 被授予。有趣的是，授予的心脏保护程度并不完全取决于 体液免疫的实现，突出了发现并从临床受益的更多机会 预防性治疗，既有复杂的，也有不一致的效果。现在越来越多的证据表明 内源性免疫-炎症途径的上游介质可能是 个人层面对接种疫苗的反应并从中受益。这些分子介体 全身性免疫炎症活动，称为二十烷基类化合物，包括一系列不同的小生物活性脂类 它们是从多不饱和脂肪酸中酶促产生的。根据初步研究的结果，我们 假设特定的二十烷类化合物不仅可以预测对流感疫苗的免疫反应，而且 还可以预测其对不良心血管事件的保护作用，而与感染状态无关。 因此，我们建议对NHLBI资助的流感疫苗进行辅助研究，以有效阻止 心胸事件和失代偿性心力衰竭(INSTED)试验，旨在：(1)确定 二十烷类化合物可预测流感疫苗接种患者的经典体液抗体应答 慢性心血管疾病，他们是不良事件风险最高的人群；以及， (2)确定在接种疫苗后产生的二十烷类化合物对应于降低的风险 心血管事件，与体液免疫和感染状态无关。现有的基础设施 这项投入的试验为接触流感高危人群提供了一种经济高效的方式-- 相关事件并实现严格的研究设计，以调查对和的反应的异质性 从接种疫苗中受益。

Project Summary In the midst of emerging threats from sporadic viral entities, the perennial influenza viral strains continue to impose a substantial burden of morbidity and mortality that compounds total annual risks to the population at large. Last season (2018-19), influenza affected 35.5 million and led to 490,600 hospitalizations and 34,200 deaths in the U.S. These vital statistics have been steadily rising each year. Individuals with cardiovascular disease are especially susceptible to the morbidity and mortality associated community-acquired viral infections such as influenza. Vaccination significantly reduces the incidence of cardiovascular events at the population level; However, administration of influenza vaccination at the individual level is extremely variable with respect to (i) the extent of humoral antibody response achieved, and (ii) the degree of cardioprotection conferred. Intriguingly, the degree of cardioprotection conferred does not depend entirely on the level of humoral immunity achieved, highlighting further opportunities to discover and derive clinical benefit from a preventive therapy with both complex and non- uniform effects. Accumulating evidence now indicates that upstream mediators of endogenous immune- inflammatory pathways are likely key determinants of the individual-level response to and benefit from an administered vaccination. These molecular mediators of systemic immune-inflammatory activity, termed eicosanoids, include a diverse family of small bioactive lipids that are enzymatically derived from polyunsaturated fatty acids. Based on results from preliminary studies, we hypothesize that specific eicosanoids not only predict the immunologic response to influenza vaccination but also predict its conferred protection from adverse cardiovascular events, irrespective of infection status. Therefore, we propose an ancillary study for the NHLBI-funded INfluenza Vaccine to Effectively Stop cardioThoracic Events and Decompensated heart failure (INVESTED) trial, that aims to: (1) identify eicosanoids that predict the classic humoral antibody response to influenza vaccination in patients with chronic cardiovascular disease, who represent the population subset most at-risk for adverse events; and, (2) identify eicosanoids generated in response to vaccination that correspond with reduced risk for cardiovascular events, irrespective of humoral immunity and infection status. The existing infrastructure of the INVESTED trial offers a cost-effective way to reach individuals who are at the highest risk for influenza- associated events and enable a rigorous study design for investigating heterogeneity in the response to and benefit from vaccination.