Active Immunotherapy with 12-mer Aβ1-42-like Assembly Vaccine Shows Efficacy in Aged 3×Tg-AD Mice
Autor: | Hao Fang, Guo Zhou, Xiaobin Pang, Qing-Li Li, Yunzhou Yu, Hai-Chao Wang, Qing Xu |
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Rok vydání: | 2021 |
Předmět: |
T-Lymphocytes
medicine.medical_treatment Protein subunit Mice Transgenic Active immunotherapy Biochemistry Epitope Mice Cognition Antigen Alzheimer Disease medicine Animals Senile plaques Molecular Biology Amyloid beta-Peptides biology business.industry Immunogenicity Immunotherapy Active General Medicine Immunotherapy Peptide Fragments Mice Inbred C57BL Disease Models Animal Vaccines Subunit Immunology biology.protein Cytokines Molecular Medicine Female Antibody business |
Zdroj: | Current Molecular Medicine. 21:45-55 |
ISSN: | 1566-5240 |
Popis: | Background: Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder characterized by senile plaques and neurofibrillary tangles (NFTs). The amyloid-oligomer hypothesis indicates that the buildup of toxic oligomers in vivo is likely to impair memory and synaptic function. Methods: In our study, a kind of novel recombinant chimeric 12×(Aβ1-15-Th) antigen was developed as 12-mer Aβ1-42-like assembly vaccine. We designed this 12×(Aβ1-15- Th) antigen to mimic the assembly states of Aβ1-42 using twelvefold Aβ1–15 (B cell epitopes of human Aβ1-42) and foreign human T helper (Th) epitopes (as the T cell epitopes of Aβ1-42) constructs. Its immunogenicity as a subunit vaccine was tested on C57/BL6 mice, and the efficacy was shown by applying it to AD mice. Results: This 12×(Aβ1-15-Th) vaccine induced robust Aβ-specific antibodies in 3×Tg- AD and C57/BL6 mice. As early immunotherapeutic agent of AD, the 12×(Aβ1-15-Th) vaccine significantly improved the behavior performance of aged 3 × Tg-AD mice, and reduced the levels of soluble Aβ oligomers and soluble Aβ in the brain. In aged 3 × Tg- AD mice, immunotherapy with the 12×(Aβ1-15-Th) vaccine could prevent Aβ-induced decrease of synaptic proteins, which suggested that it had neuroprotective effects on the brain. Conclusion: The novel recombinant 12×(Aβ1-15-Th) chimeric vaccine targeting of pathological conformations of Aβ oligomers has shown obvious neuroprotective benefits in the preclinical AD model mouse, which indicates that it is a good candidate vaccine for the prophylaxis of AD. |
Databáze: | OpenAIRE |
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