Characterization of Tau vaccines identifies diverse antibody binding profiles and efficacy, demonstrating that specific forms of Tau can be targeted by vaccines with subsequent functional impact.

Abstract

AbstractBackgroundImmunotherapy has become a tractable path for Alzheimer’s disease therapies. One of the impediments of these therapies is their intrinsic limitation of targeting, particularly regarding Tau. It is unclear to what degree these therapies target the specific disease‐causing Tau form in each individual patient at the required time in disease progression. To address these challenges, Vaxxinity is developing a vaccine derived immunotherapy targeting Tau.MethodVaccines were designed by selecting various peptide sequences along the Tau protein, conjugating to Vaxxinity’s UBTh1 peptide and formulating with CpG and Adju‐Phos. Immunogenicity of vaccines were quantified in guinea pigs and mice by ELISA. Vaccine derived antibodies were characterized by Western Blot, dot blot, immunohistochemistry and Bio‐Layer Interfereometry. Vaccine efficacy was characterized by examining the effects of vaccine derived antibodies with in vitro assays (Tau aggregation and spreading) and quantifying Tau accumulation in the brains of vaccinated mice.ResultVaccines induced robust immunogenicity with high titers. Antibodies derived from vaccines exhibited diverse binding profiles, including the production of antibodies binding preferential Tau species and those appearing to bind total Tau. Efficacy was also observed within the in vitro assays, including reduction of Tau aggregation and spreading. Modest reduction of Tau accumulation was observed in mice, with more analysis pending.ConclusionHere we present early‐stage data illustrating that the Vaxxinity platform can target a range of Tau forms in a single vaccine. Animals vaccinated with a vaccine targeting Tau produce robust antibodies against a range of Tau forms (monomeric, oligomeric and fibrils), exhibiting high titers, selectivity, and avidity. Moreover, efficacy data from animal models support the potential for future efficacy in humans.