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• W2896464239 abstract "Canines may suffer a syndrome of cognitive dysfunction associated with aging that is considered a natural (non-transgenic) model of Alzheimer's Disease which has been used to test several amyloid targeting therapies. Here we present the results of a randomised, double-blind, placebo-controlled, parallel group study of ABvac40 in dogs to assess immunogenicity and changes in plasma Aβ biomarkers. ABvac40 is an active vaccine against Aβ40 which has shown favourable results in Phase I. A Phase II clinical trial on ABvac40 is currently ongoing in France, Italy, Spain and Sweden. Twelve young dogs were subcutaneously injected with either ABvac40 (N=8) or placebo (n=4) in days D0, D14 and D28. Blood samples were collected on days D0 (before vaccination), and D7, D21, D35, D42 and D56. Levels of specific anti-Aβ40 antibodies were assessed by titration ELISAs. Free in plasma (FP) and total in plasma (TP) levels of Aβ40 and Aβ42 were quantified using ABtest (Araclon Biotech, Zaragoza, Spain). In the context of this immunization experiment, the TP level of Aβ in plasma is the amount of peptide bound to plasma components, with the exclusion of those bound to the specific anti-Aβ40 antibodies which probably escape detection by ABtest, plus the peptide found free in plasma. At each visit, the increment in antibody titers and peptide levels from baseline in the ABvac40 and placebo groups were compared by Mann-Whitney test. All the dogs receiving ABvac40 developed specific anti-Aβ40 antibodies. At D21, levels of FP40 experienced a substantial but transient increase, returning to pre-immune levels at D35. Levels of TP40 were also dramatically increased at D21 but, interestingly, they remained elevated until D42, longer than FP40 levels. In addition, the FP40/TP40 ratio was significantly reduced from D21 onwards, compared to the pre-immune levels. Neither specific anti-Aβ40 antibodies nor changes in the Aβ plasma levels were observed in the placebo group. Treatment of dogs with ABvac40 elicits the production of anti-Aβ40 specific antibodies and increase the plasma levels of Aβ40 suggesting a positive action on its target molecule, which makes our vaccine ABvac40 a promising candidate for AD prevention and early treatment." @default.
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• W2896464239 date "2018-07-01" @default.
• W2896464239 modified "2023-10-16" @default.
• W2896464239 title "P4‐189: ABVAC40 TREATMENT IN DOGS INDUCES SPECIFIC ANTIBODY RESPONSE AND INCREMENT OF Aβ40 LEVELS IN PLASMA" @default.
• W2896464239 doi "https://doi.org/10.1016/j.jalz.2018.06.2594" @default.
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