Novel Phospho-Tau Monoclonal Antibody Generated Using a Liposomal Vaccine, with Enhanced Recognition of a Conformational Tauopathy Epitope

Autor: David T. Hickman, Natalia Crespo-Biel, Herman Devijver, Maria Pihlgren, Valerie Gafner, Oskar Adolfsson, Fred Van Leuven, Peter Borghgraef, Andrea Pfeifer, Clara Theunis, Andreas Muhs, Kasia Piorkowska
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Antibody Affinity
Peptide
Plasma protein binding
Epitope
Epitopes
0302 clinical medicine
Protein structure
Antibody Specificity
Phosphorylation
Cells
Cultured
chemistry.chemical_classification
Neurons
Vaccines
General Neuroscience
Antibodies
Monoclonal
Brain
General Medicine
Recombinant Proteins
Psychiatry and Mental health
Clinical Psychology
Tauopathy
Antibody
Alzheimer’s disease
Research Article
Protein Binding
medicine.drug_class
Tau protein
Mice
Transgenic
tau Proteins
Biology
Monoclonal antibody
Antibody binding sites
03 medical and health sciences
protein conformation
medicine
Animals
Humans
Hybridomas
tauopathies
Neuropil Threads
medicine.disease
Molecular biology
Disease Models
Animal
030104 developmental biology
chemistry
monoclonal antibody
Liposomes
biology.protein
Geriatrics and Gerontology
030217 neurology & neurosurgery
Zdroj: Journal of Alzheimer's Disease
ISSN: 1875-8908
1387-2877
Popis: The microtubule-associated protein Tau is an intrinsically unfolded, very soluble neuronal protein. Under still unknown circumstances, Tau protein forms soluble oligomers and insoluble aggregates that are closely linked to the cause and progression of various brain pathologies, including Alzheimer's disease. Previously we reported the development of liposome-based vaccines and their efficacy and safety in preclinical mouse models for tauopathy. Here we report the use of a liposomal vaccine for the generation of a monoclonal antibody with particular characteristics that makes it a valuable tool for fundamental studies as well as a candidate antibody for diagnostic and therapeutic applications. The specificity and affinity of antibody ACI-5400 were characterized by a panel of methods: (i) measuring the selectivity for a specific phospho-Tau epitope known to be associated with tauopathy, (ii) performing a combination of peptide and protein binding assays, (iii) staining of brain sections from mouse preclinical tauopathy models and from human subjects representing six different tauopathies, and (iv) evaluating the selective binding to pathological epitopes on extracts from tauopathy brains in non-denaturing sandwich assays. We conclude that the ACI-5400 antibody binds to protein Tau phosphorylated at S396 and favors a conformation that is typically present in the brain of tauopathy patients, including Alzheimer's disease.
Databáze: OpenAIRE
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