Trained immunity in the prevention of viral myocarditis and pancreatitis
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Principal Investigator: Jay Reddy Organization: UNIVERSITY OF NEBRASKA LINCOLN Fiscal Year: 2022 Award: $217,570 Funding agency: National Institute of Allergy and Infectious Diseases PROJECT SUMMARY/ABSTRACT Enteroviruses, such as group B Coxsackieviruses, are common suspects in myocarditis and pancreatitis. However, no vaccines are currently available for these viruses, in part because multiple serotypes of Coxsackieviruses can induce similar diseases. Thus, exploration of alternative strategies to protect against them may have merit. The research team has made an unexpected observation that animals immunized with complete Freund’s adjuvant (CFA) were completely protected from both myocarditis and pancreatitis induced with Coxsackievirus B3 (CVB) pointed to a possibility that trained immunity may be an underlying mechanism of CFA-mediated effects, as demonstrated with the Bacillus Calmette-Guérin (BCG). The long-term goal of this research is to identify adjuvants that induce trained immunity to enhance anti-viral vaccine responses in the prevention of enteroviral infections. The objective of this application is to determine if macrophages primed with CFA mediate trained immunity. The central hypothesis is that the CFA contributes to the induction of anti-viral responses by trained immunity. This hypothesis will be tested by two specific aims: 1) characterize anti-viral responses in animals immunized with CFA and 2) determine the mechanisms of CFA- mediated protection in CVB infection. Methods and tools to be used include multiplex cytokine bead array, virus neutralization test, and major histocompatibility complex class II dextramers to assess antigen-specific immune responses and chromatin immunoprecipitation and metabolite assays to investigate the mechanisms of CFA-induced trained immunity. The project is innovative because it aims to determine whether trained immunity offers protection against CVB infections. The proposed studies are significant because they will: 1) mechanistically investigate whether trained immunity is sufficient to prevent enterovirus infections and 2) identify pathways that contribute to CFA-induced trained immunity. These outcomes may have a significant impact on strategies for preventing and/or treating viral infections using mycobacterial components that are known to possess immune-stimulating properties. Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Address><Adjuvant><Affect><Animals><Anti-Viral Response><Antigens><Antiviral Response><Assay><Attention><BCG Live><Bacille Calmette-Guérin><Bacillus Calmette Guérin><Bacteria><Bioassay><Biologic Assays><Biological Assay><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Blood monocyte><Brain Inflammation><Brittle Diabetes Mellitus><COVID><COVID-19><COVID-19 virus><COVID19><COVID19 virus><CV-19><CV19><Cell Body><Cells><ChIP assay><Class II Antigens><Class II Major Histocompatibility Antigens><CoV disease><CoV-2><CoV2><Congestive Cardiomyopathy><Coxsackie B Viruses><Coxsackie Viruses><Coxsackievirus><Coxsackieviruses B><Cytotoxic cell><Data><Derivation><Derivation procedure><Development><Dilated Cardiomyopathy><Disease><Disease Outbreaks><Disorder><Encephalitis><Enterovirus><Enterovirus Infections><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Exanthem><Exanthema><Exposure to><Foot-and-Mouth Disease><Foundations><Freund's Adjuvant><Freund's Complete Adjuvant><Future><Gamma-delta T cells><Genus Mycobacterium><Goals><Health><Heart><Histocompatibility Antigens Class II><Histologic><Histologically><Human><I-A Antigen><IDDM><Ia Antigens><Ia-Like Antigens><Immune><Immune Response Antigens><Immune response><Immune-Response-Associated Antigens><Immunes><Immunity><Immunization><Immunize><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunostimulation><Individual><Infant><Infection><Insulin-Dependent Diabetes Mellitus><Juvenile-Onset Diabetes Mellitus><K lymphocyte><Ketosis-Prone Diabetes Mellitus><Lipopolysaccharides><M tb><M tuberculosis><M. tb><M. tuberculosis><MHC Class II Molecule><MHC Class II Protein><MHC class II antigen><Macromolecular Structure><Major Histocompatibility Complex Class II><Marrow Neutrophil><Marrow monocyte><Mediating><Memory><Meningitis><Metabolic><Methods><Mission><Modern Man><Molecular><Molecular Structure><Morbidity><Morbidity - disease rate><Mycobacterium><Mycobacterium tuberculosis><Myocarditis><Mφ><NIH><NK Cells><National Institutes of Health><Natural Killer Cells><Neutralization Tests><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Outbreaks><Outcome><Palsy><Pancreas><Pancreatic><Pancreatitis><Paralysed><Parasites><Pathogenicity><Pathway interactions><Patients><Plegia><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Prevention><Property><Public Health><Rash><Research><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Serotyping><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Skin Rash><Stimulus><Sudden-Onset Diabetes Mellitus><T1 DM><T1 diabetes><T1D><T1DM><Testing><Therapeutic Uses><Training><Type 1 Diabetes Mellitus><Type 1 diabetes><Type I Diabetes Mellitus><United States><United States National Institutes of Health><Vaccine Adjuvant><Vaccinee><Vaccines><Viral><Viral Diseases><Viral Gene Products><Viral Gene Proteins><Viral Proteins><Viral Vaccines><Virus><Virus Diseases><Wuhan coronavirus><adaptive immune response><antibody neutralization test><beta-Glucans><cardiac inflammation><chromatin immunoprecipitation><corona virus disease><corona virus disease 2019><coronavirus disease><coronavirus disease 2019><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><cytokine><developmental><diabetic cardiomyopathy><diabetic cardiopathy><diabetic cardiopathy disease><diabetic cardiopathy disorder><diabetic cardiovascular disease><diabetic cardiovascular disorder><gene function><hCoV19><host response><immune system response><immunogen><immunoresponse><improved><incomplete Freund's adjuvant><innovate><innovation><innovative><insulin dependent diabetes><insulitis><juvenile diabetes><juvenile diabetes mellitus><ketosis prone diabetes><macrophage><microbial><monocyte><mortality><mtb><mycobacterial><nCoV2><neutrophil><non vaccinated><not vaccinated><novel><paralysis><paralytic><pathway><prevent><preventing><respiratory><response><small molecule><success><tool><type I diabetes><type one diabetes><unvaccinated><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination study><vaccination trial><vaccine candidate><vaccine response><vaccine responsiveness><vaccine strategy><vaccine study><vaccine trial><vaccine-induced response><viral infection><viral myocarditis><virus infection><virus protein><virus-induced disease><β-Glucans><γδ T cells><γδT cells>