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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结