Limits...
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

Health monitoring of non-transgenic mice (control, ▼, n = 19) and P301S mice treated with a placebo (♦, n = 20), Tau199–208[pS202/pT205] (, n = 15), Tau209–217[pT212/pS214] (, n = 16), or Tau229–237[pT231/pS235] (, n = 20). (A) body weight; (B) photograph of a paralyzed P301S mouse; (C) survival rates; (D) percentage of paralysis. Statistical significances are marked by asterisks (***, p < 0.001).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4494214&req=5

vaccines-02-00601-f007: Health monitoring of non-transgenic mice (control, ▼, n = 19) and P301S mice treated with a placebo (♦, n = 20), Tau199–208[pS202/pT205] (, n = 15), Tau209–217[pT212/pS214] (, n = 16), or Tau229–237[pT231/pS235] (, n = 20). (A) body weight; (B) photograph of a paralyzed P301S mouse; (C) survival rates; (D) percentage of paralysis. Statistical significances are marked by asterisks (***, p < 0.001).

Mentions: The animal behavior was tested with the same group of P301S mice (n = 20 per test group) at the age of 20, 32, and 48 weeks. At all ages, non-transgenic mice (control) were significantly, up to 28%, heavier than age-matched transgenic mice (Figure 7A). With an average weight of 25 g there was no significant difference in body weight between vaccinated and placebo-treated transgenic P301S mice. All animals underwent a health monitoring at each point of analysis. The phenotype of clasping and limb retractions was also recorded, but was not statistical significant (data not shown).


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)

Health monitoring of non-transgenic mice (control, ▼, n = 19) and P301S mice treated with a placebo (♦, n = 20), Tau199–208[pS202/pT205] (, n = 15), Tau209–217[pT212/pS214] (, n = 16), or Tau229–237[pT231/pS235] (, n = 20). (A) body weight; (B) photograph of a paralyzed P301S mouse; (C) survival rates; (D) percentage of paralysis. Statistical significances are marked by asterisks (***, p < 0.001).
© Copyright Policy
Related In: Results  -  Collection

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

vaccines-02-00601-f007: Health monitoring of non-transgenic mice (control, ▼, n = 19) and P301S mice treated with a placebo (♦, n = 20), Tau199–208[pS202/pT205] (, n = 15), Tau209–217[pT212/pS214] (, n = 16), or Tau229–237[pT231/pS235] (, n = 20). (A) body weight; (B) photograph of a paralyzed P301S mouse; (C) survival rates; (D) percentage of paralysis. Statistical significances are marked by asterisks (***, p < 0.001).
Mentions: The animal behavior was tested with the same group of P301S mice (n = 20 per test group) at the age of 20, 32, and 48 weeks. At all ages, non-transgenic mice (control) were significantly, up to 28%, heavier than age-matched transgenic mice (Figure 7A). With an average weight of 25 g there was no significant difference in body weight between vaccinated and placebo-treated transgenic P301S mice. All animals underwent a health monitoring at each point of analysis. The phenotype of clasping and limb retractions was also recorded, but was not statistical significant (data not shown).

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