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Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy
Open accessAbstract
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.
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“Active tau immunization has been shown to reduce tau pathology by targeting single185, 187, 189–193 or multiple194 phospho-epitopes, the amino terminus195, full-length normal and mutant tau196, 197, or aggregated tau198.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [190]
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“Cytokine production of pTau/Tau peptides or Tau proteinspecific T cells was assessed by ELISPOT as previously described [24].”
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“pre-clinical models for neuronal tauopathy [12,30–38].”
BackgroundInfluentialSelf-citationMenuet, C., Borghgraef, P., Matarazzo, V. A., Gielis, L., Lajard, A.-M., Voituron, N., Gestreau, C., Dutschmann, M., LEUVEN, F. V., & Hilaire, G. (2011) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2011.06.030 · Cited by 35 · cited 5×
“pre-clinical models for neuronal tauopathy [12,30–38].”
BackgroundInfluentialSelf-citationRECENT DEVELOPMENTS IN ALZHEIMER’S DISEASE
Cras, P. P. (2001) · Acta Clinica Belgica · doi:10.1179/acb.2001.040 · Cited by 33
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Immunotherapy and Neuroimmunology in Alzheimer‘s Disease: a Perspective from The Blood–Brain Barrier
Banks, W. A. (2009) · Immunotherapy · doi:10.2217/imt.09.72 · Cited by 15 · cited 2×
“Moreover, in AD and other neurological disorders, the BBB is compromised which might allow antibodies to enter the CNS more readily [47–53].”
BackgroundBinding specificity of monoclonal antibody AD2: influence of the phosphorylation state of tau
Torreilles, F., Roquet, F., Granier, C., Pau, B., & Mourton-Gilles, C. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00073-5 · Cited by 10 · cited 1×
“AD2 and PHF1 among others, are located in this region [25–29].”
BackgroundFuture of Immunotherapy: A Call for Comparative Immunology
Marincola, F. M. (2008) · Immunotherapy · doi:10.2217/1750743x.1.1.1 · Cited by 5
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“Phase I clinical trials have started and ACI-35 is currently undergoing phase Ib clinical trials in patients suffering from this common form of dementia [56,59].”
Background
Metadata
- Authors
- Theunis, C., Crespo-Biel, N., Gafner, V., Pihlgren, M., López-Deber, M. P., Reis, P., Hickman, D. T., Adolfsson, O., Chuard, N., Ndao, D. M., Borghgraef, P., Devijver, H., Van Leuven, F., Pfeifer, A., & Muhs, A.
- Affiliations
- KU Leuven (BE)
- AC Immune (Switzerland) (CH)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-08-19
- Volume
- 8
- Issue
- 8
- Pages
- e72301
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3747157
- OpenAlex
- W2090968981
- Cited by
- 259
- References
- 78
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 25 · 2023: 17 · 2022: 22 · 2021: 23 · 2020: 25 · 2019: 23 · 2018: 27 · 2017: 22 · 2016: 19 · 2015: 13 · 2014: 16 · 2013: 1
- FWCI
- 11.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau protein, tau immunotherapy, tauopathy, Alzheimer's disease, vaccine safety, neuroinflammation, tau aggregation
- MeSH terms
- Animals, Brain, Disease Models, Animal, Humans, Liposomes, Mice, Transgenic, Peptides, Phosphoproteins, Phosphorylation, Psychomotor Performance, Vaccination, tau Proteins, Treatment Outcome, Alzheimer Vaccines, Tauopathies, Mice, Antibodies, Neutralizing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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