| 摘要 |
Disclosed are novel methods for combating diseases characterised by deposition of amyloid. The methods generally rely on immunisation against amyloidogenic proteins (proteins contributing to formation of amyloid) such as beta amyloid (Abeta). Immunisation is preferably effected by administration of analogues of autologous amyloidogenic polypeptides, the analogues being capable of inducing antibody production against the autologous amyloidogenic polypeptides. Especially preferred, as an immunogen is autologous Abeta, which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes while substantially preserving the majority of Abeta 's B-cell epitopes. Also disclosed are nucleic acid vaccination against amyloidogenic polypeptides and vaccination using live vaccines as well as methods and means useful for the vaccination. Such methods and means include methods for identification of useful immunogenic analogues of the amyloidgonic proteins, methods for the preparation of analogues and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations. The figure is a schematic depiction of Autovac variants derived from the amyloid precursor protein with the purpose of generating antibody responses against the A, protein Ass-43 (or C- 100). The APP is shown schematically at the top of the figure and the remaining schematic constructs show that the model epitopes P2 and P30 are substituted or inserted into various truncations of APP. In the figure, the black pattern indicates the APP signal sequence, two-way cross- hatching is the extracellular part of APP; dark vertical hatching is the transmembrane domain of APP; light vertical hatching is the intracellular domain of APP, coarse cross- hatching indicates the P30 epitope, and fine cross-hatching indicates the P2 epitope. The full line box indicates "Abeta-42/43" and the full-line box and the dotted line box together indicate C-100."Abeta".
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