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

Richter M, Mewes A, Fritsch M, Krügel U, Hoffmann R, Singer D - Vaccines (Basel) (2014)

Bottom Line: 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.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.In conclusion, the data provide strong evidence that active immune therapies can reduce toxic effects of deposits formed in AD.

View Article: PubMed Central - PubMed

Affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, Leipzig 04103, Germany. monique_richter@gmx.de.

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 with the increased survival rates undoubtedly prove the treatment effect. In conclusion, the data provide strong evidence that active immune therapies can reduce toxic effects of deposits formed in AD.

No MeSH data available.


Related in: MedlinePlus

Time scale of the applied immunization protocol and behavioral tests, as well as the time points of immunoblot and immunohistochemical analysis, we = weeks.
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vaccines-02-00601-f001: Time scale of the applied immunization protocol and behavioral tests, as well as the time points of immunoblot and immunohistochemical analysis, we = weeks.

Mentions: Female mice were immunized with freshly prepared vaccine formulations. Peptides were dissolved in sterile Tris buffer (10 mmol/L, pH 7.4, 1 g/L), mixed (1:1, v:v) with Alu-GelS as adjuvant (Serva Electrophoresis, Heidelberg, Germany) and allowed to absorb onto the aluminum particles overnight at 4 °C on a tube rotator [13]. Mice were primed the next day subcutaneously at multiple sites followed by two intraperitoneal boosts 14 and 42 days afterwards (Figure 1). The immune response was evaluated by blood samples that were taken submandibular seven to ten days after each immunization and thereafter every four weeks for the next eight months. Red blood cells were removed by centrifugation (6700× g, 90 s) and the supernatant containing the serum was stored at −20 °C.


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

Richter M, Mewes A, Fritsch M, Krügel U, Hoffmann R, Singer D - Vaccines (Basel) (2014)

Time scale of the applied immunization protocol and behavioral tests, as well as the time points of immunoblot and immunohistochemical analysis, we = weeks.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494214&req=5

vaccines-02-00601-f001: Time scale of the applied immunization protocol and behavioral tests, as well as the time points of immunoblot and immunohistochemical analysis, we = weeks.
Mentions: Female mice were immunized with freshly prepared vaccine formulations. Peptides were dissolved in sterile Tris buffer (10 mmol/L, pH 7.4, 1 g/L), mixed (1:1, v:v) with Alu-GelS as adjuvant (Serva Electrophoresis, Heidelberg, Germany) and allowed to absorb onto the aluminum particles overnight at 4 °C on a tube rotator [13]. Mice were primed the next day subcutaneously at multiple sites followed by two intraperitoneal boosts 14 and 42 days afterwards (Figure 1). The immune response was evaluated by blood samples that were taken submandibular seven to ten days after each immunization and thereafter every four weeks for the next eight months. Red blood cells were removed by centrifugation (6700× g, 90 s) and the supernatant containing the serum was stored at −20 °C.

Bottom Line: 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.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.In conclusion, the data provide strong evidence that active immune therapies can reduce toxic effects of deposits formed in AD.

View Article: PubMed Central - PubMed

Affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, Leipzig 04103, Germany. monique_richter@gmx.de.

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 with the increased survival rates undoubtedly prove the treatment effect. In conclusion, the data provide strong evidence that active immune therapies can reduce toxic effects of deposits formed in AD.

No MeSH data available.


Related in: MedlinePlus