Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau Aggregation
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/pThr2...
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MDPI AG
2014-07-01
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| Series: | Vaccines |
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| Online Access: | http://www.mdpi.com/2076-393X/2/3/601 |
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| author | Monique Richter Agneta Mewes Manuela Fritsch Ute Krügel Ralf Hoffmann David Singer |
| author_facet | Monique Richter Agneta Mewes Manuela Fritsch Ute Krügel Ralf Hoffmann David Singer |
| author_sort | Monique Richter |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T04:46:13Z |
| format | Article |
| id | doaj.art-0e912756b11c4b84b5b8319539f2f11e |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-14T04:46:13Z |
| publishDate | 2014-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-0e912756b11c4b84b5b8319539f2f11e2022-12-22T02:11:27ZengMDPI AGVaccines2076-393X2014-07-012360162310.3390/vaccines2030601vaccines2030601Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau AggregationMonique Richter0Agneta Mewes1Manuela Fritsch2Ute Krügel3Ralf Hoffmann4David Singer5Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, Leipzig 04103, GermanyInstitute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, Leipzig 04103, GermanyInstitute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, Leipzig 04103, GermanyRudolf Boehm Institute for Pharmacology and Toxicology, Universität Leipzig, Leipzig 04107, GermanyInstitute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, Leipzig 04103, GermanyInstitute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, Leipzig 04103, GermanyIntracellular 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.http://www.mdpi.com/2076-393X/2/3/601Alzheimer’s diseaseimmunizationpeptide vaccinephospho-tautransgenic mouse modelP301S mice |
| spellingShingle | Monique Richter Agneta Mewes Manuela Fritsch Ute Krügel Ralf Hoffmann David Singer Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau Aggregation Vaccines Alzheimer’s disease immunization peptide vaccine phospho-tau transgenic mouse model P301S mice |
| title | Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau Aggregation |
| title_full | Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau Aggregation |
| title_fullStr | Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau Aggregation |
| title_full_unstemmed | Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau Aggregation |
| title_short | Doubly Phosphorylated Peptide Vaccines to Protect Transgenic P301S Mice against Alzheimer’s Disease Like Tau Aggregation |
| title_sort | doubly phosphorylated peptide vaccines to protect transgenic p301s mice against alzheimer s disease like tau aggregation |
| topic | Alzheimer’s disease immunization peptide vaccine phospho-tau transgenic mouse model P301S mice |
| url | http://www.mdpi.com/2076-393X/2/3/601 |
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