O1‐10‐03: an Active Anti‐AB40 Vaccine (ABVAC40) Proved to be Safe and Immunogenic in the Phase i Clinical Trial

Abstract

with Ab42 plus adjuvant (AN1792, Elan Pharmaceuticals) or placebo were studied. Comprehensive neuropathological assessments were performed ranging from 4 months to 14 years after the trial. Large coronal paraffin sections of cerebral hemisphere were immunostained for Ab, scanned, then (i) the entire neocortical ribbon was scored for plaques in a CERAD-like manner (frequent¼3, moder-ate¼2, sparse¼1, none¼0) and (ii) false coloured to permit visualisation of staining patterns at low power. Results: 16/21 had a distribution of tangles and at least some residual Ab pathology indicating the cause of dementia had been AD, whereas 5/21 had alternative causes for dementia (PSP¼1, DLB¼1, VaD¼1and FTD-TDP43¼2). 18/21 had received the active agent and 3/21 the placebo. Scanning and false colouration of large Ab immunostained sections generated images suitable for comparison with amyloid PET scans as used in current immunotherapy trials. 13/15 AD subjects receiving the active agent had evidence of plaque removal (almost complete removal¼5, extensive patches of removal¼4, small patches of removal¼4, no plaque removal¼2). In the immunised AD group the mean plaque score was 1.46 (range¼0.05-2.9) vs. 2.4 for the single placebo AD case. There was a significant inverse correlation between peripheral blood anti-Ab titres and plaque scores. Conclusions: AD patients actively immunised against Ab can remain virtually plaque-free for up to 14 years. Nearly a quarter of the patients examined in this study did not have neuropathologically verified AD. Neuropathology follow up of patients in therapeutic trials for AD provides valuable information on the cause of dementia and effects of treatment.