title: 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.
authors: Experimental Genetics Group, Department Human Genetics, KU Leuven, Leuven, Belgium.
authors: Clara
authors: C
authors: Theunis
authors: Natalia
authors: N
authors: Crespo-Biel
authors: Valérie
authors: V
authors: Gafner
authors: Maria
authors: M
authors: Pihlgren
authors: María Pilar
authors: MP
authors: López-Deber
authors: Pedro
authors: P
authors: Reis
authors: David T
authors: DT
authors: Hickman
authors: Oskar
authors: O
authors: Adolfsson
authors: Nathalie
authors: N
authors: Chuard
authors: Dorin Mlaki
authors: DM
authors: Ndao
authors: Peter
authors: P
authors: Borghgraef
authors: Herman
authors: H
authors: Devijver
authors: Fred
authors: F
authors: Van Leuven
authors: Andrea
authors: A
authors: Pfeifer
authors: Andreas
authors: A
authors: Muhs
mesh_terms: D023582:Alzheimer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D010750:Phosphoproteins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D010766:Phosphorylation; D011597:Psychomotor Performance / Q000187:drug effects; D024801:Tauopathies / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016896:Treatment Outcome; D014611:Vaccination; D016875:tau Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*
chemical_list: D023582:Alzheimer Vaccines; D057134:Antibodies, Neutralizing; D008081:Liposomes; D010455:Peptides; D010750:Phosphoproteins; D016875:tau Proteins
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