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Principal Investigator: David Scott Wilson
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2024
Award: $491,250
Funding agency: National Institute of Allergy and Infectious Diseases
1. Abstract: The number of patients with autoimmunity and other antigen-specific immunoregulatory
disorders is increasing worldwide at a rate of 4 to 8% per annum. Current therapies for autoimmunity only
treat disease symptoms and are systemically immunosuppressive, resulting in an increased risk of infection
and malignancy. The Holy Grail of autoimmune therapies would specifically abrogate pathogenic
autoantigen-specific immune response. To this end, we propose the development of a novel biomaterial-
based intranasal antigen-specific immunotherapy engineered to elicit auto-antigen specific regulatory T
cells that control autoimmunity. Our in intranasal AIST is composed of autoantigens conjugated to a water-
soluble polymer that binds to nasal mucus, facilitates paracellular transport across the nasal epithelium, and
targets autoantigens and tolerance-programming small molecules (i.e., minocycline and dexamethasone) to
underlying nasal DCs, resulting in the induction of autoantigen-specific regulatory T cells that suppress
autoimmune responses. In this application, we propose: (1) the synthesis of our novel intranasal ASIT, (2)
the demonstration of the ability of our platform to suppress antigen-specific immune responses, and (3) the
use of our platform to treat and prevent experimental autoimmune myocarditis. Completion of this project
will deliver a clinically viable treatment for autoimmune myocarditis and a therapeutic platform that can be
easily tailored to treat other diseases driven by antigen-specific immune dysregulation, including diabetes,
multiple sclerosis, transplant rejection, and numerous allergies.
Terms: <Allergens><Allergic><Allergic Disease><Allergy><American><Animal Model><Animal Models and Related Studies><Antigens><Autoantigens><Autoimmune><Autoimmune Diseases><Autoimmune Responses><Autoimmune Status><Autoimmune cardiomyopathy><Autoimmune myocarditis><Autoimmune-mediated myocarditis><Autoimmunity><Autologous Antigens><Binding><Biocompatible Materials><Biomaterials><CD25><Cancers><Cardiac><Cardiac Muscle Myosins><Cardiac Myosins><Clinical><Congestive Cardiomyopathy><Dendritic Cells><Development><Dexamethasone><Diabetes Mellitus><Dilated Cardiomyopathy><Disease><Disorder><Disseminated Sclerosis><Engineering><Epithelium><Experimental Models><Fibrosis><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Formulation><Goals><Graft Rejection><Histology><Hydrogen Oxide><Hypersensitivity><IL2R><IL2RA><IL2RA gene><Image Cytometry><Immune><Immune infiltrates><Immune mediated therapy><Immune response><Immune system><Immunes><Immunize><Immunological response><Immunologically Directed Therapy><Immunomodulation><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Immunotherapy><Infection><Inflammatory><Infusion><Infusion procedures><Injections><Intranasal Administration><Intranasal Drug Administration><Label><Liver><Lymphatic Tissue><Lymphoid Tissue><Malignant Neoplasms><Malignant Tumor><Measures><Mediating><Mercaptans><Mercapto Compounds><Mice><Mice Mammals><Minocycline><Molecular Interaction><Mucous body substance><Mucus><Multiple Sclerosis><Murine><Mus><Myocarditis><Nasal><Nasal Epithelium><Nasal Passages Nose><Nose><Occluding Junctions><Opportunistic Infections><Ovalbumin><Pain><Painful><Pathogenicity><Pathology><Patient Compliance><Patients><Peptides><Phagocytes><Phagocytic Cell><Phenotype><Phosphatidylserines><Play><Polymers><Pre-Clinical Model><Preclinical Models><Receptor Protein><Regulatory T-Lymphocyte><Respiratory System, Nose, Nasal Passages><Risk><Self-Antigens><Serine Phosphoglycerides><Severities><Signal Induction><Sulfhydryl Compounds><Symptoms><T-Cells><T-Lymphocyte><TCGFR><Technology><Therapeutic><Thiols><Tight Junctions><Transplant Rejection><Transplantation Rejection><Treg><Veiled Cells><Water><Work><Zonula Occludens><amebocyte><autoimmune condition><autoimmune disorder><autoimmunity disease><biological material><cardiac function><cardiac inflammation><clinical translation><clinically translatable><design><designing><developmental><di-block copolymer><diabetes><diblock copolymer><efficacy validation><flow cytophotometry><function of the heart><heart function><hepatic body system><hepatic organ system><host response><immune cell infiltrate><immune modulation><immune regulation><immune suppression><immune suppressive activity><immune suppressive function><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><immunogen><immunologic reactivity control><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><immunosuppressive activity><immunosuppressive function><immunosuppressive response><infection risk><infusions><insular sclerosis><malignancy><model of animal><monomer><mouse model><mucous><murine model><neoplasm/cancer><non-human primate><nonhuman primate><novel><patient adherence><patient cooperation><polymer><polymeric><pre-clinical><preclinical><prevent><preventing><programs><receptor><regulatory T-cells><response><small molecule><sulfhydryl group><technology platform><technology system><thymus derived lymphocyte><validate efficacy><whole animal imaging>