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Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy
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 problema...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747157/ https://www.ncbi.nlm.nih.gov/pubmed/23977276 http://dx.doi.org/10.1371/journal.pone.0072301 |
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author | Theunis, Clara Crespo-Biel, Natalia Gafner, Valérie Pihlgren, Maria López-Deber, María Pilar Reis, Pedro Hickman, David T. Adolfsson, Oskar Chuard, Nathalie Ndao, Dorin Mlaki Borghgraef, Peter Devijver, Herman Van Leuven, Fred Pfeifer, Andrea Muhs, Andreas |
author_facet | Theunis, Clara Crespo-Biel, Natalia Gafner, Valérie Pihlgren, Maria López-Deber, María Pilar Reis, Pedro Hickman, David T. Adolfsson, Oskar Chuard, Nathalie Ndao, Dorin Mlaki Borghgraef, Peter Devijver, Herman Van Leuven, Fred Pfeifer, Andrea Muhs, Andreas |
author_sort | Theunis, Clara |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3747157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37471572013-08-23 Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy Theunis, Clara Crespo-Biel, Natalia Gafner, Valérie Pihlgren, Maria López-Deber, María Pilar Reis, Pedro Hickman, David T. Adolfsson, Oskar Chuard, Nathalie Ndao, Dorin Mlaki Borghgraef, Peter Devijver, Herman Van Leuven, Fred Pfeifer, Andrea Muhs, Andreas PLoS One Research Article 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. Public Library of Science 2013-08-19 /pmc/articles/PMC3747157/ /pubmed/23977276 http://dx.doi.org/10.1371/journal.pone.0072301 Text en © 2013 Theunis et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Theunis, Clara Crespo-Biel, Natalia Gafner, Valérie Pihlgren, Maria López-Deber, María Pilar Reis, Pedro Hickman, David T. Adolfsson, Oskar Chuard, Nathalie Ndao, Dorin Mlaki Borghgraef, Peter Devijver, Herman Van Leuven, Fred Pfeifer, Andrea Muhs, Andreas Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy |
title | Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy |
title_full | Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy |
title_fullStr | Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy |
title_full_unstemmed | Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy |
title_short | Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy |
title_sort | efficacy and safety of a liposome-based vaccine against protein tau, assessed in tau.p301l mice that model tauopathy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747157/ https://www.ncbi.nlm.nih.gov/pubmed/23977276 http://dx.doi.org/10.1371/journal.pone.0072301 |
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