MultiTEP‐based conjugated vaccines targeting various phosphorylated tau epitopes are immunogenic and effective in the PS19 mouse model

Pathological tau correlates well with cognitive impairments in Alzheimer’s disease (AD) patients and represents a promising immunotherapy target. In theory, targeting an appropriate B‐cell epitope in pathological tau could effectively reduce the pathology without affecting normal native tau. Hyperphosphorylation of tau is a well‐known feature of Alzheimer’s and other tauopathies, with many disease‐specific phosphorylation sites documented. Accordingly, we attached several disease‐related phosphorylated tau peptides to our universal vaccine platform, MultiTEP that is safe and extremely immunogenic in various disease models of AD, rabbits, and aged monkeys. We hypothesized that high immunogenicity of MultiTEP‐based vaccines, coupled with the selectivity of the immune responses, will allow the identification of pathological and protective phosphorylation sites, thus leading to the generation of vaccines, which would preferentially clear the toxic forms of tau without disrupting the normal brain homeostasis.