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: 10608977
• 负责人: Susan Cheng
• 金额: $ 72.7万
• 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/10608977
• 关键词: Acute; Address; Adult; Affect; Ancillary Study; Anti-Inflammatory Agents; Antibody Response; Antibody titer measurement; Antigens; Biological Assay; Biological Response Modifiers; Cardiovascular Diseases; Cardiovascular Models; Cardiovascular system; Cell physiology; Cells; Cessation of life; Chronic; Circulation; Clinical; Communities; Complex; Congestive Heart Failure; Cytometry; Data; Dose; Eicosanoid Modulation; Eicosanoids; 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; Lipids; Mass Spectrum Analysis; Mediating; Mediator; 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; Populations at Risk; 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; 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; participant enrollment; 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.

项目摘要 在来自零星病毒实体的新兴威胁中，多年生流感病毒株继续 强大的发病率和死亡率负担，将年度总风险累及 大的。上个赛季（2018-19），流感影响了3550万，导致490,600次住院和34,200 美国的死亡人数每年都在稳步上升。患有心血管的人 疾病特别容易受到与社区获得的病毒相关的发病率和死亡率 感染，例如流感。疫苗接种大大降低了心血管事件的发生率 人口水平；但是，在单个水平上给予流感疫苗接种是极其可变的 关于（i）达到体液抗体反应的程度，以及（ii）心脏保护程度 授予。有趣的是，赋予的心脏保护程度并不完全取决于 实现了体液免疫力，突出了进一步的机会发现并从 具有复杂和非均匀作用的预防疗法。现在积累证据表明 内源性免疫 - 炎症途径的上游介体可能是主要决定因素 个人级别的反应并受益于管理疫苗接种。这些分子介体的 全身免疫炎性活性称为类类酸性，包括一个多样的小生物活性脂质家族 酶从多不饱和脂肪酸中得出。根据初步研究的结果，我们 假设特定的类花生酸不仅预测了对流感疫苗接种的免疫学反应，还可以预测 还可以预测其对不良心血管事件的保护保护，而不论感染状况如何。 因此，我们为NHLBI资助的流感疫苗提出了一项辅助研究，以有效停止 旨在：（1）确定的心胸胸膜事件和不足的心力衰竭（投资）试验（投资）试验 预测患有流感疫苗的经典体液抗体反应的类花生酸酯对患者的流感疫苗接种 慢性心血管疾病，代表人口子集对不良事件的最高风险；和， （2）确定响应于疫苗接种而产生的类花生酸，这与降低的风险相对应 心血管事件，不论体液免疫和感染状况如何。现有的基础设施 这项投资试验提供了一种具有成本效益的方式，可以吸引那些对流感风险最高风险的个人 相关事件并启用了严格的研究设计，以调查对响应的异质性和 受益于疫苗接种。