Anti-abeta therapeutic vaccines
Inventors
Fiorini, Emma • Vukicevic Verhille, Marija • Pihlgren Bosch, Maria
Assignees
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Publication Number
US-12005102-B2
Publication Date
2024-06-11
Expiration Date
Abstract
A liposomal vaccine composition comprises a β-amyloid (Aβ)-derived peptide antigen displayed on the surface of the liposome. The vaccine composition also comprises a peptide comprising a universal T-cell epitope encapsulated within the liposome. The vaccine composition also comprises an adjuvant, which may form part of the liposome and may be displayed at least in part on the surface of the liposome. These vaccine compositions are used for treating, preventing, inducing a protective immune response against or alleviating the symptoms associated with an amyloid-beta associated disease or condition or a condition characterised by, or associated with, loss of cognitive memory capacity in a subject. The vaccine compositions may be provided as a kit. Related methods of producing a liposomal vaccine composition are also provided.
Core Innovation
The invention provides anti-amyloid-beta (Aβ) liposomal therapeutic vaccines that display an Aβ-derived B-cell peptide antigen on the surface of a liposome. The Aβ-derived antigen can be tetrapalmitoylated and can comprise amino acids 1-15 of Aβ, and the liposome composition further includes an adjuvant that may associate with or be displayed on the liposome surface.
To provide helper T-cell stimulation, the liposome encapsulates a peptide comprising a universal T-cell epitope. The encapsulated universal T-cell epitope peptide stimulates a helper T-cell response that enhances antibody production by B-cells, and the universal T-cell epitope peptide uses defined epitope sequence options from tetanus, influenza hemagglutinin, diphtheria, KLH, and Epstein Barr virus domains.
The disclosed liposomal vaccine formulations include anionic liposomes and representative phospholipid/cholesterol mixtures, together with adjuvants such as MPLA and CpG. The disclosed approach is directed to treatment and prevention of amyloid-beta associated diseases and cognitive impairment conditions, and the document reports improved immune readouts including increased Aβ-specific IgG titers and avidity maturation, inhibition of Aβ1-42 self-association, and oligomer recognition.
Claims Coverage
The document includes three independent claims covering liposomal vaccine compositions. Across these independent claims, the inventive coverage centers on a liposome surface-displayed Aβ-derived antigen, an encapsulated universal T-cell epitope peptide that stimulates helper T-cell responses and enhances antibody production by B-cells, and an adjuvant.
Aβ-derived peptide antigen displayed on the surface of a liposome
A β-amyloid (Aβ)-derived peptide antigen displayed on the surface of a liposome.
Encapsulated universal T-cell epitope peptide that enhances antibody production by B-cells
A peptide comprising a universal T-cell epitope encapsulated within the liposome that stimulates a helper T-cell response that enhances antibody production by B-cells, with dependent claim sets specifying particular sequence/domain combinations and sequence identifiers.
Adjuvant included in the liposomal vaccine composition
An adjuvant in the liposomal vaccine composition.
Tetrapalmitolyated Aβ-derived peptide antigen comprising amino acids 1-15
A tetrapalmitolyated β-amyloid (Aβ)-derived peptide antigen displayed on the surface of the liposome that comprises, consists essentially of or consists of amino acids 1-15 of Aβ.
Encapsulated universal T-cell epitope peptide having amino acid sequence of SEQ ID NO: 3 (SAT44)
A peptide comprising a universal T-cell epitope encapsulated within the liposome wherein the peptide comprises an amino acid sequence of SEQ ID NO: 3 (SAT44).
Tetrapalmitolyated Aβ-derived peptide antigen and encapsulated universal T-cell epitope peptide having amino acid sequence of SEQ ID NO: 4 (SAT47)
A tetrapalmitolyated β-amyloid (Aβ)-derived peptide antigen displayed on the surface of the liposome that comprises, consists essentially of or consists of amino acids 1-15 of Aβ; and a peptide comprising a universal T-cell epitope encapsulated within the liposome wherein the peptide comprises, consists essentially of or consists of an amino acid sequence of SEQ ID NO: 4 (SAT47).
Across the independent claims, the core claim coverage is a liposomal vaccine composition that couples a β-amyloid (Aβ)-derived peptide antigen displayed on the liposome surface with an encapsulated peptide comprising a universal T-cell epitope. The composition further includes an adjuvant, and dependent claim sets refine the compositions by specifying particular universal T-cell epitope sequence identifiers and adjuvant options.
Stated Advantages
Enhanced antibody production by B-cells via a helper T-cell response.
Increased Aβ-specific IgG titers and avidity maturation.
Inhibition of Aβ1-42 self-association.
Oligomer recognition, including Aβ oligomer-specific IgG.
Documented Applications
Treating and preventing amyloid-beta associated diseases and conditions, including Alzheimer’s disease and cognitive impairment conditions.
Inducing a protective immune response against amyloid-beta associated disease or condition.
Alleviating symptoms associated with an amyloid-beta associated disease or condition.
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