Oct 31, 2019

A MultiTEP platform-based epitope vaccine targeting the phosphatase activating domain (PAD) of tau: therapeutic efficacy in PS19 mice

Scientific Reports
Armine HovakimyanHayk Davtyan

Abstract

Pathological tau correlates well with cognitive impairments in Alzheimer's disease (AD) patients and therefore represents a promising target for immunotherapy. Targeting an appropriate B cell epitope in pathological tau could in theory produce an effective reduction of pathology without disrupting the function of normal native tau. Recent data demonstrate that the N-terminal region of tau (aa 2-18), termed the "phosphatase activation domain (PAD)", is hidden within native Tau in a 'paperclip'-like conformation. Conversely, PAD is exposed in pathological tau and plays an essential role in the inhibition of fast axonal transport and tau polymerization. Thus, we hypothesized that anti-tau2-18 antibodies may safely and specifically reduce pathological tau and prevent further aggregation, which in turn would neutralize tau toxicity. Therefore, we evaluated the immunogenicity and therapeutic efficacy of our MultiTEP platform-based vaccine targeting tau2-18 formulated with AdvaxCpG adjuvant (AV-1980R/A) in PS19 tau transgenic mice. The AV-1980R/A induced extremely high antibody responses and the resulting sera recognized neurofibrillary tangles and plaque-associated dystrophic neurites in AD brain sections. In addition, under non-dena...Continue Reading

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Mentioned in this Paper

Axonal Transport
Phosphoric Monoester Hydrolases
Neurofibrillary Degeneration (Morphologic Abnormality)
Immunologic Adjuvants
Vaccines
7-(6-N-phenylaminohexyl)amino-2H-anthra(1,9-cd)pyrazol-6-one
Brain
Protein Phosphatase Activity
Antibodies, Neutralizing
Alzheimer's Disease

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