The first tau-directed vaccine tested in clinical trials was AADvac1, developed by Axon Neuroscience SE. The vaccine development approach used a truncated tau protein (151–391/4R) hypothesized to be the pathologic fragment triggering misfolding and aggregation. [92] A novel monoclonal antibody (DC8E8) was raised against this fragment and found to disrupt the tau-tau interactions that lead to pathologic tau agreggation [93]. The specific epitope for DC8E8 was found to be in the MTBR repeat region, and AADvac1 was developed by attaching a peptide fragment recapitulating the structural epitope to a carrier protein that drives a B-cell mediated immune response. In transgenic rat models expressing truncated tau protein, AADvac1 reduced tau aggregation and improved sensorimotor function [94].
