Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer's Disease Like Tau Aggregation

Vaccines
Monique RichterDavid Singer

Abstract

Intracellular neurofibrillary tangles and extracellular senile plaques are potential targets for active and passive immunotherapies. In this study we used the transgenic mouse model P301S for active immunizations with peptide vaccines composed of a double phosphorylated tau neoepitope (pSer202/pThr205, pThr212/pSer214, pThr231/pSer235) and an immunomodulatory T cell epitope from the tetanus toxin or tuberculosis antigen Ag85B. Importantly, the designed vaccine combining Alzheimer's disease (AD) specific B cell epitopes with foreign (bacterial) T cell epitopes induced fast immune responses with high IgG₁ titers after prophylactic immunization that subsequently decreased over the observation period. The effectiveness of the immunization was surveyed by evaluating the animal behavior, as well as the pathology in the brain by biochemical and histochemical techniques. Immunized mice clearly lived longer with reduced paralysis than placebo-treated mice. Additionally, they performed significantly better in rotarod and beam walk tests at the age of 20 weeks, indicating that the disease development was slowed down. Forty-eight weeks old vaccinated mice passed the beam walk test significantly better than control animals, which together w...Continue Reading

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Citations

Apr 1, 2017·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Xiaoli WuKin Yip Tam
Feb 16, 2019·Acta Neuropathologica Communications·Santosh JadhavNorbert Zilka
Apr 24, 2020·Current Topics in Medicinal Chemistry·Md Tanvir KabirGhulam Md Ashraf
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Methods Mentioned

BETA
transgenic
PCR
biopsies
ELISA
Electrophoresis

Software Mentioned

ImageJ
TSE RotaRod
GraphPad Prism

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