6Aβ15-T

6Aβ15-T is a recombinant protein-based vaccine designed for active immunotherapy against Alzheimer's disease. The construct consists of **six copies of the Aβ1-15 peptide** (the immunodominant B-cell epitope of Aβ42) linked together with GS small linkers, creating a hexavalent foldable structure[1]. The T-cell epitopes of Aβ42 have been replaced with **PADRE** (a pan HLA-DR binding epitope) or toxin-derived carrier proteins to provide foreign T helper epitopes, designed to overcome Aβ-associated hyporesponsiveness while avoiding autoimmune T-cell responses[1][3]. The vaccine is expressed and purified in *Escherichia coli* (BL21) and has been formulated with alum adjuvant[1]. When administered, 6Aβ15-T effectively elicits high titers of anti-Aβ antibodies that bind more strongly to Aβ oligomers than to monomers, but not to Aβ42 fibrils[1]. This oligomer-specific targeting is considered therapeutically advantageous for Alzheimer's disease treatment. In preclinical studies using **PDAPP** and **3×Tg-AD** mouse models, 6Aβ15-T vaccination induced sustained high levels of Aβ-specific IgG antibodies (187 ± 63 μg/ml in PDAPP mice and 218 ± 52 μg/ml in 3×Tg-AD mice)[1]. The vaccine demonstrated capacity to reduce amyloid pathology, inhibit amyloid accumulation, and prevent cognitive dysfunction in aged AD model mice[1][3][7]. A novel **co-immunization strategy** combining DNA and protein forms of 6Aβ15-T (without adjuvant) has been developed to induce robust Th2-polarized antibody responses while suppressing unwanted inflammatory T-cell reactions[3]. This approach successfully overcomes Aβ42-associated hyporesponsiveness and provides long-term antibody responses.

Other names

hexavalent foldable Aβ1-156Aβ15-T vaccine6Aβ15-T antigen