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Pyroglutamate amyloid beta3–42 (pGlu-Abeta3–42), a highly amyloidogenic and neurotoxic form of Abeta, is N-terminally truncated to form a pyroglutamate and has recently been proposed as a key target for immunotherapy. Optimized ACI-24, a vaccine in development for the treatment and prevention of Alzheimer’s disease, focuses the antibody response on the first 15 N-terminal amino acids of Abeta (Abeta1–15). Importantly, clinical data with an initial version of ACI-24 incorporating Abeta1–15, established the vaccine’s safety and tolerability with evidence of immunogenicity. To explore optimized ACI-24’s capacity to generate antibodies to pGlu-Abeta3–42, pre-clinical studies were carried out. Vaccinating mice and non-human primates demonstrated that optimized ACI-24 was well-tolerated and induced an antibody response against Abeta1–42 as expected, as well as high titres of IgG reactive with …