Nucleic acids for treatment of allergies

Inventors

Hearl, William • Heiland, Teri

Assignees

Immunomic Therapeutics Inc

Abstract

The present invention provides DNA vaccines for the treatment of allergies. The vaccines comprise the coding sequence for one or more allergenic epitopes, and preferably the full protein sequence, of the allergenic protein from which the epitope(s) is derived, fused inframe with the lumenal domain of the lysosomal associated membrane protein (LAMP) and the targeting sequence of LAMP. The vaccines allow for presentation of properly configured three dimensional epitopes for production of an immune response. The vaccines can be multivalent molecules, and/or can be provided as part of a multivalent vaccine containing two or more DNA constructs.

Core Innovation

The document discloses DNA vaccine constructs for allergic disease in which an allergen polypeptide is engineered as an in-frame fusion with the lumenal domain of lysosomal associated membrane protein (LAMP) and a LAMP targeting sequence. The allergen can comprise a full-length allergen or an epitopic or truncated form, and the construct removes the native signal sequence of the allergen. The LAMP targeting design directs intracellular trafficking to lysosome/endosome compartments so that proper processing occurs for MHC class II presentation.

An intra-organelle stabilizing domain is used as part of the chimeric polypeptide architecture, together with an endosome/lysosome targeting domain including a transmembrane domain and a cytoplasmic lysosome/endosome targeting domain. The disclosed construct architecture is aimed at biasing an immune response toward IgG and Th1 rather than an IgE and Th2 response. The document includes evaluation through MHC-II pathway comparisons and reporting of cytokine patterns consistent with Th1 versus Th2 bias.

The disclosure further provides DNA vaccine constructs for food allergy, including a peanut multi-allergen construct that combines multiple peanut allergens (AraH1, AraH2, AraH3) into a single poly-protein construct fused to LAMP-related targeting elements. The document describes expression and detection for the disclosed engineered chimeric polypeptides and gives construct examples including Cry J2-LAMP, Cry J1+Cry J2-LAMP, and AraH1/AraH2/AraH3-LAMP. The document emphasizes outcome measures such as absence of free allergen in circulation after LAMP-based vaccination and reported efficacy in sensitized animal models after challenge.

Claims Coverage

The partial content includes two independent claims, both directed to treating a peanut allergy by administering an isolated or purified nucleic acid molecule encoding a polypeptide with the amino acid sequence of SEQ ID NO: 9. Across the independent claims, the core inventive coverage is the use of that specific SEQ ID NO: 9 encoding nucleic acid administered as a pharmaceutically effective amount, with dependent claims further specifying nucleic acid format and an immunologic outcome.

Both independent claims cover methods of treating peanut allergy in a subject using a pharmaceutically effective amount of an isolated or purified nucleic acid molecule encoding a polypeptide with the amino acid sequence of SEQ ID NO: 9. The claim set further narrows coverage in dependents by specifying DNA and/or an expression vector and by requiring reduction of IgE response.

Stated Advantages

Documented Applications