Timothy grass allergens and methods and uses for immune response modulation
Inventors
Sette, Alessandro • Schulten, Veronique • Grey, Howard • Peters, Bjoern • Greenbaum, Jason
Assignees
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Publication Number
US-10428124-B2
Publication Date
2019-10-01
Expiration Date
Abstract
The invention relates to Timothy Grass proteins and peptides, subsequences, portions, homologs, variants and derivatives thereof, and methods and uses of Timothy Grass proteins and peptides. Methods include, for example, modulating an immune response; protecting a subject against or treating a subject for an allergic response, allergic disorder or allergic disease; and inducing immunological tolerance to the allergen in a subject.
Core Innovation
The invention relates to Timothy grass (TG) proteins and peptides, including variants, derivatives, and epitope-containing subsequences, for modulating immune responses in a subject. The disclosed approach emphasizes that TG Th2/T-cell responses can target novel antigens that are not necessarily IgE-reactive, linking TG T-cell epitopes to immunological modulation rather than IgE reactivity.
The problem being solved is allergic disease associated with grass pollen, including grass pollen allergy, allergic rhinitis, and asthma, where immune responses are modulated to induce immunological tolerance. The disclosure frames a method for increasing immunological tolerance against grass pollen by administering an effective amount of a peptide comprising at least one T-cell epitope or an effective amount of a protein, such that the administered TG sequence induces, elicits, or stimulates interleukin-5 or interferon-gamma production in peripheral blood mononuclear cells from grass allergic subjects.
The document further supports the stated concept with identifying novel TG pollen proteins/antigens and evaluating IL-5 responses. It describes antigenome discovery workflows that integrate transcriptomics and proteomics to identify novel TG pollen proteins/antigens, and it reports ex vivo recognition involving memory T cells and IL-5 producing T cells, providing evidence that specific TG antigens can elicit functional T-cell cytokine responses relevant to tolerance and allergic disease modulation.
Claims Coverage
The independent claims cover two administration modalities: peptides and proteins, each defined by TG sequence selections and each producing an IL-5 or IFN-gamma response in peripheral blood mononuclear cells from grass-allergic subjects, with the objective of increasing immunological tolerance against grass pollen.
Peptide for inducing tolerance against grass pollen
A method for increasing immunological tolerance against grass pollen in a subject comprising administering at least once an effective amount of a peptide comprising at least one T-cell epitope, the peptide consisting of an amino acid sequence selected from SEQ ID NOS: 854, 855, and 857-868, wherein the peptide induces, elicits or stimulates production of interleukin-5 or interferon-gamma in peripheral blood mononuclear cells from grass allergic subjects following contact with the peptide.
Protein for inducing tolerance against grass pollen
A method for increasing immunological tolerance against grass pollen in a subject comprising administering at least once an effective amount of a protein consisting of an amino acid sequence selected from SEQ ID NOS: 177-186, wherein the protein induces, elicits or stimulates production of interleukin-5 or interferon-gamma in peripheral blood mononuclear cells from grass allergic subjects following contact with the protein.
Both independent claims require administration of a defined TG peptide or TG protein sequence, where contact with the administered TG component induces, elicits, or stimulates IL-5 or interferon-gamma production in peripheral blood mononuclear cells from grass-allergic subjects, for increasing immunological tolerance against grass pollen.
Stated Advantages
Increases immunological tolerance against grass pollen in a subject.
Peptides or proteins induce, elicit, or stimulate interleukin-5 or interferon-gamma production in peripheral blood mononuclear cells from grass allergic subjects, supporting modulation of immune responses relevant to allergic disease.
Provides treatment and/or protection against allergic diseases associated with grass pollen, including grass pollen allergy, allergic rhinitis, and asthma.
Documented Applications
Treat or protect against grass pollen allergy.
Treat or protect against allergic rhinitis.
Treat or protect against asthma.
The document provides a catalog/table of predicted timothy grass (TG) allergen-derived peptide sequences derived from transcriptomically identified proteins, listing peptide occurrences across protein IDs and start-stop positions.
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