Vaccine Induced Immune-Inflammatory Response and Cardiovascular Risk

疫苗诱导的免疫炎症反应和心血管风险

• 批准号: 10378764
• 负责人: Susan Cheng
• 金额: $ 72.92万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10378764
• 关键词: Acute; Address; Adult; Affect; Ancillary Study; Anti-Inflammatory Agents; Antibody Response; Antibody titer measurement; Antigens; Biological Assay; Biological Response Modifiers; Blood Circulation; Cardiovascular Diseases; Cardiovascular Models; Cardiovascular system; Cell physiology; Cells; Cessation of life; Chronic; Clinical; Communities; Complex; Cytometry; Data; Dose; Eicosanoids; Enrollment; Event; Exposure to; Family; Framingham Heart Study; Funding; Heart failure; Heterogeneity; Hospitalization; Human; Humoral Immunities; Immune; Immune response; Immune system; In Vitro; Incidence; Individual; Individual Differences; Infection; Inflammation Mediators; Inflammatory; Inflammatory Response; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza vaccination; Infrastructure; Laboratories; Light; Lipids; Mass Spectrum Analysis; Mediating; Mediator of activation protein; Methods; Molecular; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Natural Immunity; Participant; Pathway interactions; Patients; Pattern; Persons; Phenotype; Pilot Projects; Plasma; Polyunsaturated Fatty Acids; Population; Predisposition; Preventive therapy; Randomized Controlled Trials; Research Design; Resistance; Risk; Role; Sampling; Seasons; Specimen; Stimulus; Stress; Testing; Time; Vaccination; Vaccines; Validation; Variant; Viral; Virus Diseases; Vital Statistics; adaptive immunity; adverse event risk; adverse outcome; base; cardioprotection; cardiovascular disorder risk; cardiovascular risk factor; clinically relevant; co-infection; cohort; cost effective; exhaustion; hazard; high risk; human data; improved; in vivo; influenza infection; influenza virus strain; influenza virus vaccine; mortality; mouse model; novel coronavirus; pre-clinical; response; stem; treatment response; trial design; vaccination outcome

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.

项目概要 在零星病毒实体不断出现的威胁中，常年性流感病毒株继续传播 造成了沉重的发病率和死亡率负担，加剧了人口的年度总风险 大的。上个季节（2018-19），流感影响了 3550 万人，导致 490,600 人住院，34,200 人死亡 美国的死亡人数这些重要统计数据每年都在稳步上升。有心血管疾病的人 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 流感等感染。疫苗接种可显着降低心血管事件的发生率 人口水平；然而，个人层面的流感疫苗接种情况差异很大 关于 (i) 达到的体液抗体反应程度，以及 (ii) 心脏保护程度 授予。有趣的是，心脏保护的程度并不完全取决于 实现了体液免疫，强调了进一步发现和从中获得临床益处的机会 预防性治疗具有复杂且不一致的效果。现在积累的证据表明 内源性免疫炎症途径的上游介质可能是炎症反应的关键决定因素 个人水平对接种疫苗的反应并从中受益。这些分子介质 全身免疫炎症活性，称为类二十烷酸，包括多种小生物活性脂质 是由多不饱和脂肪酸酶促衍生的。根据初步研究的结果，我们 假设特定的类二十烷酸不仅可以预测对流感疫苗接种的免疫反应，而且可以预测 还可以预测其对不良心血管事件的保护作用，无论感染状况如何。 因此，我们建议对 NHLBI 资助的流感疫苗进行一项辅助研究，以有效阻止 心胸事件和失代偿性心力衰竭 (INVESTED) 试验，旨在：(1) 确定 类花生酸可预测流感患者对流感疫苗的经典体液抗体反应 慢性心血管疾病，他们是最容易发生不良事件的人群；和， (2) 确定因疫苗接种而产生的类二十烷酸，这些类二十烷酸与降低的风险相对应 心血管事件，无论体液免疫和感染状态如何。现有基础设施 所投资的试验提供了一种经济有效的方法来接触流感风险最高的个人 相关事件，并能够进行严格的研究设计，以调查响应和事件的异质性 受益于疫苗接种。