Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy

Abstract

Progressive aggregation of protein Tau into oligomers and fibrils correlates with cognitive decline and synaptic dysfunction, leading to neurodegeneration in vulnerable brain regions in Alzheimer's disease. The unmet need of effective therapy for Alzheimer's disease, combined with problematic pharmacological approaches, led the field to explore immunotherapy, first against amyloid peptides and recently against protein Tau. Here we adapted the liposome-based amyloid vaccine that proved safe and efficacious, and incorporated a synthetic phosphorylated peptide to mimic the important phospho-epitope of protein Tau at residues pS396/pS404. We demonstrate that the liposome-based vaccine elicited, rapidly and robustly, specific antisera in wild-type mice and in Tau.P301L mice. Long-term vaccination proved to be safe, because it improved the clinical condition and reduced indices of tauopathy in the brain of the Tau.P301L mice, while no signs of neuro-inflammation or other adverse neurological effects were observed. The data corroborate the hypothesis that liposomes carrying phosphorylated peptides of protein Tau have considerable potential as safe and effective treatment against tauopathies, including Alzheimer's disease.

Tau immunotherapy for Alzheimer's disease

“…The first efficacious active [42] and [46]. These beneficial effects were not associated with any adverse inflammatory response, suggesting a good safety profile for human studies.…”

Update on Alzheimer's Disease Therapy and Prevention Strategies

“…Two active immunization vaccines ( Table 1) are currently in clinical trials: AADvac-1 (Axon Neuroscience SE), a tau 294-305 linked to keyhole limpet hemocyanin with an N-terminal cysteine, and ACI-35 (AC Immune SA, Janssen Pharmaceutica), a tau 393-408 (pS396, pS404) tetra-palmitoylated phospho-tau peptide (70,71).…”

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

“…84,85 Although the scope of this review is on liposome-strategies with the aim of facilitating BBB crossing, it is important to mention that other strategies have been developed for the use of liposomes for AD treatment. 89,[113][114][115][116] Curcumin is a natural compound extract from the plant Curcuma longa, and has been reported to be a fluorescent molecule with high affinity for the Aβ peptide and able to reduce Aβ aggregation. In this way, intracranial injection of liposomes encapsulating curcumin efficiently labeled Aβ deposits in both human and mice tissues, proving to be an effective formulation for diagnosis and treatment of AD.…”