Composition for enhancing immunity comprising immune modulator and cationic liposome, and use of same
Inventors
Cho, Yang Je • Kim, Kwangsung • Lee, Na Gyong • Park, Shin Ae
Assignees
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Publication Number
US-10874733-B2
Publication Date
2020-12-29
Expiration Date
Abstract
The present invention relates to an immunity enhancing composition including an immune response modulator having a novel structure and, more specifically, to an immunity enhancing composition and a use of the same, wherein the immunity enhancing composition includes a lipopolysaccharide (LPS) analogue with reduced toxicity, and a cationic liposome. The present invention overcomes the physicochemical instability of a liposome, is advantageous in terms of production, transportation, and storage, and improves stability, thus being beneficial as an immune delivery system. In addition, the present invention includes an immune response modulator, and a cationic liposome, and thus exhibits an enhanced immunity-improving effect compared to the case in which an immune response modulator is used alone.
Core Innovation
The invention relates to an immunity-enhancing composition comprising an immune modulator represented by Formula 1 and a cationic liposome. Formula 1 contains Glc, GlcN, HEP, KDO, and GlcNAc, and includes phosphate groups bonded at selected positions including C, E, CD, CE, DE, and CDE. The composition is defined by the specific phosphate-bonding pattern within the LPS-derived immune modulator framework combined with a cationic liposome.
The immune modulator is described as a detoxified LPS-derived immune modulator, EG-IM/LOS deacylated and reduced toxicity, used together with a cationic liposome to form an immunity-enhancing composition. The liposome formulation improves liposome stability for production, transport, and storage, including freeze-dried or lyophilized formulations.
The document also describes vaccine-format embodiments in which an antigen is included with the immunity-enhancing composition as an active ingredient. Vaccine compositions can be provided in lyophilized or ready-to-use forms, and the document describes lyophilization and rehydration concepts, including an additional lyophilization after antigen addition.
Claims Coverage
The document identifies one independent claim defining an immunity-enhancing composition with two main inventive features: a Formula 1 immune modulator with phosphate groups at selected positions and a cationic liposome. Dependent claims refine the cationic liposome composition and expand coverage to vaccine compositions by adding an antigen, and also include a preparation workflow for a vaccine composition with an additional lyophilization step.
Formula 1 immune modulator with phosphate-bonded positions
An immune modulator represented by Formula 1 comprising Glc, GlcN, HEP, KDO, and GlcNAc, with each phosphate bonded at a position selected from C, E, CD, CE, DE, and CDE.
Cationic liposome
A composition for enhancing immunity further comprising a cationic liposome.
Cationic lipid selected from enumerated cationic lipids
The composition includes a cationic liposome in which the cationic lipid is selected from the group of specified cationic lipid molecules.
Neutral lipid selected from enumerated neutral phospholipids
The cationic liposome further includes a neutral lipid selected from the group of specified neutral phospholipids.
Vaccine composition with antigen as active ingredient
A vaccine composition containing an antigen and including the composition for enhancing immunity as an active ingredient.
Antigen selected from antigen types
The vaccine composition includes an antigen selected from the group including peptide, protein, nucleic acid, sugar, pathogen, attenuated pathogen, inactivated pathogen, virus, virus-like particle, cell, and cell fragment.
Vaccine preparation with solvent dissolution, lyophilization and rehydration, antigen addition, and second lyophilization
A method preparing a vaccine composition by preparing an immune modulator solution of Formula 1, forming a liposome from a lipid by dissolving in an organic solvent, lyophilizing and rehydrating, then combining the immune modulator solution with an antigen on the liposome and lyophilizing again.
Overall, claim coverage centers on an immunity-enhancing composition combining a phosphate-bonded Formula 1 immune modulator with a cationic liposome, with dependent claims specifying particular cationic and optional neutral lipid members and expanding to vaccine compositions by adding an antigen selected from enumerated antigen types. Additional dependent coverage includes a specific vaccine preparation workflow that culminates in a second lyophilization after antigen addition.
Stated Advantages
Improved liposome stability for production, transport, and storage, including freeze-dried or lyophilized formulations.
Synergistic immune enhancement versus EG-IM alone.
Enhanced immune cell proliferation and TNF-α induction.
Reduced cationic-liposome cytotoxicity.
Vaccine performance in mouse models with improved antibody and/or IFN-γ responses for multiple antigens.
Improved antigen uptake by dendritic cells and a depot effect.
Synergy with added lipids and with saponin adjuvant (Quil A).
Formulation-dependent immunogenicity, including lyophilized plus antigen performing better than simple mix for Th1/IFN-γ.
Documented Applications
Vaccine-format coverage for multiple antigens in mouse models, including antigens associated with Zika, JEV, TB (Ag85A/ESAT-6/HspX), pertussis (aP), and VZV (gE), with improved immune responses.
Use as a vaccine composition for multiple antigen types, including peptide, protein, nucleic acid, sugar, pathogen, attenuated or inactivated pathogen, virus, virus-like particle, cell, and cell fragment, in lyophilized or ready-to-use forms.
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