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Publication Number
US-9216215-B2
Publication Date
2015-12-22
Expiration Date
Abstract
The present invention provides adjuvant compositions that have improved stability, increased potency and which provide an enhanced Th1 response. The present invention also provides methods of making those compositions and administration of the improved adjuvant compositions.
Core Innovation
The invention relates to vaccine adjuvant compositions that combine one or more C-type lectin (CTL) receptor ligands with one or more solid aluminum adjuvants and one or more antigens. The CTL receptor ligand(s) comprise mannose-1-phosphate or phosphorylated mannan, and the CTL receptor ligand(s) are linked to the aluminum adjuvant(s) by coordinate, covalent, hydrophilic, or hydrophobic bonds. This linked formulation is described as providing an adjuvant system for antigen immunological compositions.
Aluminum adjuvants alone are described as having limitations, including a tendency to skew immune responses toward Th2 and IgG1, rather than favoring a Th1 response. The invention addresses this by targeting CTL receptors, which are associated with antigen uptake by antigen presenting cells and cross-presentation via MHC I and MHC II pathways. The approach is described as supporting a mixed or Th1-skewed immune response compared with aluminum alone.
The disclosed approach is further described as maintaining stability of the CTL ligand attachment despite exposure to phosphate. The document describes evidence of stable ligand attachment and associated enhanced antibody responses in rats, including increased total IgG and increased IgG2a and IgG2b, with examples including aluminum oxyhydroxide combined with mannose-1-phosphate or mannan.
Claims Coverage
The patent contains two independent claims covering an immunological composition and an adjuvant. Each independent claim is supported by inventive compositional features that link CTL receptor ligands (mannose-1-phosphate or phosphorylated mannan) to solid aluminum adjuvants by specified bond types, together with one or more antigens.
Linked CTL receptor ligands and solid aluminum adjuvants with antigens
An immunological composition comprising one or more C-type lectin (CTL) receptor ligands and one or more solid aluminum adjuvants and one or more antigens, wherein the CTL receptor ligand(s) comprise mannose-1-phospahte or phosphorylated mannan and are linked to the aluminum adjuvant(s) by coordinate, covalent, hydrophilic, or hydrophobic bonds.
Adjuvant comprising linked CTL receptor ligands and solid aluminum adjuvants with antigens
An adjuvant comprising one or more C-type lectin (CTL) receptor ligands and one or more solid aluminum adjuvants and one or more antigens, wherein the CTL receptor ligand(s) comprise mannose-1-phospahte or phosphorylated mannan and are linked to the aluminum adjuvant(s) by coordinate, covalent, hydrophilic, or hydrophobic bonds.
Overall, the claim scope centers on compositions and adjuvants that include antigens, solid aluminum adjuvants, and CTL receptor ligands (mannose-1-phosphate or phosphorylated mannan) linked to the aluminum adjuvants by coordinate, covalent, hydrophilic, or hydrophobic bonds. Dependent claims further specify representative aluminum solid compounds, including aluminum oxyhydroxide and related aluminum phosphates/phosphate-sulfate species, and in some cases narrow to aluminum oxyhydroxide.
Stated Advantages
Improved stability/potency of the adjuvant system by maintaining stable ligand attachment despite phosphate exposure.
Enhanced antibody/isotype responses, including increased total IgG and increased IgG2a/IgG2b.
Enhanced immune response described as mixed or Th1-skewed compared to limitations of aluminum alone.
Documented Applications
Vaccine formulations using the disclosed CTL ligand-solid aluminum adjuvant system with antigens, including in vivo potency comparisons using SpeA/B (Streptococcus pyogenes pyrogenic exotoxin A/B) in rats.
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