Title:Active Immunotherapy with 12-mer Aβ1-42-like Assembly Vaccine Shows Efficacy in Aged 3×Tg-AD Mice
Volume: 21
Issue: 1
Author(s): Hao Fang, Guo Zhou, Qingli Li, Haichao Wang, Xiaobin Pang, Qing Xu*Yunzhou Yu*
Affiliation:
- Institute of Life Science and Biotechnology, Beijing Jiaotong University, Beijing 100044,China
- Beijing Institute of Biotechnology, Beijing 100071,China
Keywords:
Alzheimer's disease, Amyloid-β, Chimeric vaccine, Immunotherapy, Calpain, Synaptic protein.
Abstract:
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.
