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Principal Investigator: Susan Cheng
Organization: CEDARS-SINAI MEDICAL CENTER
Fiscal Year: 2024
Award: $718,171
Funding agency: National Heart Lung and Blood Institute
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.
Terms: <21+ years old><Acute><Address><Adult><Adult Human><Affect><Ancillary Study><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Antibody Response><Antibody titer measurement><Antigens><Assay><Bioassay><Biological Assay><Biological Response Modifiers><Biomodulators><Blood Plasma><Cardiac Failure Congestive><Cardiovascular><Cardiovascular Body System><Cardiovascular Diseases><Cardiovascular Models><Cardiovascular Organ System><Cardiovascular system><Cell Body><Cell Function><Cell Physiology><Cell Process><Cells><Cellular Function><Cellular Physiology><Cellular Process><Cessation of life><Chronic><Circulation><Clinical><CoV emergence><Communities><Complex><Congestive Heart Failure><Cytometry><Data><Death><Dose><Eicosanoid Modulation><Eicosanoids><Event><Exposure to><Family><Flu vaccination><Framingham Heart Study><Funding><Grippe><Groups at risk><H1N1><H1N1 Virus><H3N2><H3N2 Virus><Heart Decompensation><Heart Vascular><Heart failure><Heterogeneity><Hospital Admission><Hospitalization><Human><Humoral Immunities><Immune><Immune Mediators><Immune Mediators/Modulators><Immune Regulators><Immune response><Immune system><Immunes><Immunological response><In Vitro><Incidence><Individual><Individual Differences><Infection><Inflammation Mediators><Inflammatory><Inflammatory Response><Influenza><Influenza A Virus, H1N1 Subtype><Influenza A Virus, H3N2 Subtype><Influenza Vaccines><Influenza immunization><Influenza vaccination><Infrastructure><Innate Immunity><Laboratories><Lipids><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Mediating><Mediator><Methods><Modern Man><Molecular><Morbidity><Morbidity - disease rate><NHLBI><National Heart, Lung, and Blood Institute><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Participant><Pathway interactions><Patients><Pattern><People at risk><Persons><Persons at risk><Phenotype><Pilot Projects><Plasma><Plasma Serum><Polyunsaturated Fatty Acids><Population><Populations at Risk><Predisposition><Preventative therapy><Preventive therapy><Prophylactic vaccination against influenza><Randomized, Controlled Trials><Research Design><Research Specimen><Resistance><Reticuloendothelial System, Serum, Plasma><Risk><Role><Sampling><Seasons><Specimen><Stimulus><Stress><Study Type><Subcellular Process><Susceptibility><Testing><Time><Vaccination><Vaccines><Validation><Variant><Variation><Viral><Viral Diseases><Virus Diseases><Vital Statistics><adaptive immunity><adulthood><adverse consequence><adverse event risk><adverse outcome><antibody titering><antibody-based immunity><cardiac failure><cardioprotectant><cardioprotection><cardioprotective><cardiovascular disease risk><cardiovascular disorder><cardiovascular disorder risk><cardiovascular risk><cardiovascular risk factor><chronic heart failure><circulatory system><clinical relevance><clinically relevant><co-infection><cohort><coinfection><corona virus emergence><coronavirus emergence><cost effective><emergent CoV><emergent corona virus><emergent coronavirus><emerging CoV><emerging corona virus><emerging coronavirus><exhaustion><flu immunisation><flu infection><flu serotype><flu strain><flu subtype><flu vaccine><flu viral strain><flu virus infection><flu virus strain><flu virus vaccine><hazard><high risk><host response><human data><immune response to vaccination><immune response to vaccines><immune system response><immunogen><immunomodulatory biologics><immunoresponse><improved><in vivo><infected with flu><infected with flu virus><infected with influenza><infected with influenza virus><inflammatory mediator><influenza infection><influenza serotype><influenza strain><influenza subtype><influenza viral strain><influenza virus infection><influenza virus strain><influenza virus vaccination><influenza virus vaccine><mortality><mouse model><murine model><nCoV><new CoV><new corona virus><new coronavirus><novel CoV><novel corona virus><novel coronavirus><outcome following vaccination><outcome following vaccine><participant enrollment><pathway><patient enrollment><pilot study><pre-clinical><preclinical><randomized control trial><resistant><response><response to therapy><response to treatment><result following vaccination><result following vaccine><social role><stem><study design><therapeutic response><therapy response><treatment response><treatment responsiveness><trial design><vaccination against influenza><vaccination outcome><vaccination result><vaccine against flu><vaccine against influenza><vaccine associated immune response><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><vaccine outcome><vaccine result><validations><viral infection><virus infection><virus-induced disease>