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Publication Number
US-9744230-B2
Publication Date
2017-08-29
Expiration Date
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 invention relates to DNA vaccines for allergy treatment. The constructs encode allergen epitopes or allergenic proteins, and the encoded polypeptides are chimeric proteins designed to be routed for epitope processing and presentation through the endolysosomal/MHC-II pathway.
The polypeptides include a signal sequence domain, an intra-organelle stabilizing domain fused in-frame, an allergen domain, a transmembrane domain, and a cytoplasmic LAMP targeting domain. The stabilizing domain is preferably a lumenal domain of LAMP, including LAMP-1 lumenal domain, and the cytoplasmic domain provides lysosome/endosome targeting.
The allergen domain lacks native allergen signal peptides and is fused to LAMP-derived domains to preserve three-dimensional epitope structure. The disclosure includes single and multiepitope or multiallergen constructs, including CryJ1/CryJ2 and peanut AraH1/AraH2/AraH3 (AraH-LAMP).
Claims Coverage
Independent claim coverage in the provided material is limited to a single independent claim directed to an isolated or purified nucleic acid molecule encoding a polypeptide with a specified amino acid sequence. The claims focus on one inventive feature at the independent level, with dependent claims refining nucleic-acid type, expression vector use, and pharmaceutical compositions.
Isolated or purified nucleic acid encoding SEQ ID NO: 9 polypeptide
An isolated or purified nucleic acid molecule encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 9.
DNA nucleic acid molecule
The nucleic acid molecule comprises DNA.
Expression vector comprising the DNA
An expression vector comprising the nucleic acid molecule recited in the DNA nucleic-acid feature.
Pharmaceutical composition with the expression vector
A pharmaceutical composition comprising the expression vector.
Pharmaceutical composition with pharmaceutically acceptable carrier
The pharmaceutical composition further comprising a pharmaceutically acceptable carrier.
Pharmaceutical composition comprising the nucleic acid molecule
A pharmaceutical composition comprising the nucleic acid specified by the SEQ ID NO: 9 nucleic-acid feature.
Across the claims provided, the core scope is an isolated or purified nucleic acid encoding a specified polypeptide sequence, with further coverage to DNA, an expression vector containing that DNA, and pharmaceutical compositions containing either the vector or the nucleic acid, optionally including a pharmaceutically acceptable carrier.
Stated Advantages
Enhanced IgG1 and IgG2a responses versus LAMP-negative controls.
Th1-biased cytokine profile with increased IFN-gamma and reduced IL-4.
Improved responses in previously sensitized mice.
Reduced circulating free CryJ2 in LAMP-vaccinated mice.
IgG responses in guinea pigs after challenge.
Rabbit toxicology safety observations.
Documented Applications
Allergy treatment using DNA vaccines encoding allergen epitopes or allergenic proteins routed through the endolysosomal/MHC-II pathway for epitope processing and presentation.
Use in previously sensitized mice to improve immune responses.
Challenge experiments in guinea pigs to elicit IgG responses.
Safety/toxicology observations in rabbits.
Expression and detection of a multiallergen peanut polyprotein (AraH1/AraH2/AraH3-LAMP).
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