Anti-abeta therapeutic vaccines

Inventors

Fiorini, Emma • Vukicevic Verhille, Marija • Pihlgren Bosch, Maria

Assignees

AC Immune SA

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 concerns anti-β-amyloid (Aβ) therapeutic vaccine concepts using liposomal vaccine compositions. A β-amyloid (Aβ)-derived B-cell peptide antigen is displayed on the surface of a liposome rather than presenting full-length Aβ. In the described embodiments, the antigen includes a preferred Aβ(1-15) tetrapalmitoylated form (Pal1-15), supporting an Aβ-specific antibody response.

To drive helper T-cell (CD4) activation and enhance B-cell antibody production, the liposome encapsulates a peptide comprising a universal T-cell epitope. The universal T-cell epitope peptides are specified as SEQ ID NO: 1 (SAT42), SEQ ID NO: 2 (SAT43), SEQ ID NO: 3 (SAT44), or SEQ ID NO: 4 (SAT47), and are described as typically hydrophobic. The universal T-cell epitope content can also be implemented as single epitopes or multi-epitope constructs, including linked 2–34 epitopes using lysosomal cysteine protease substrate linkers with example sequence sets including SAT42/43/44/47 and additional examples SAT6/13/15/17.

An adjuvant is included with the liposomal vaccine composition to support immune responses. The document describes lipid-associated adjuvants, including monophosphoryl lipid A (MPLA) optionally in the liposome bilayer, and provides background on other adjuvant examples such as aluminum hydroxide (Alum) and CpG. The stated overall approach is to provide improved, safer Aβ-specific antibody responses by combining surface-displayed Aβ-derived B-cell peptide antigen with encapsulated universal T-cell epitopes that stimulate helper T-cell responses.

Claims Coverage

The partial set of relevant independent claims includes two independent claims defining liposomal vaccine compositions. Across these claims, the inventive features include surface display of a β-amyloid-derived peptide antigen, encapsulation of a universal T-cell epitope peptide with defined sequence sets, and inclusion of an adjuvant, with a refinement in one independent claim to a tetrapalmitoylated Aβ(1-15) antigen.

The independent claim set is centered on a liposomal vaccine composition that combines a β-amyloid-derived peptide antigen displayed on the liposome surface with an encapsulated universal T-cell epitope peptide defined by SAT42/43/44/47 to stimulate helper T-cell responses that enhance B-cell antibody production, together with an adjuvant; one independent claim additionally requires a tetrapalmitoylated Aβ(1-15) antigen.

Stated Advantages

Documented Applications