Active Immunotherapy with 12-mer Aβ1-42-like Assembly Vaccine Shows Efficacy in Aged 3×Tg-AD Mice

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 twelve fold 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 has 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 preclinical AD model mouse, which indicates it is a good candidate vaccine for the prophylaxis of AD.

Current study on diagnosis and treatment of Alzheimer’s disease by targeting amyloid b-protein

“…This study also suggests that the Aβ derivative, when used with an adjuvant suitable for humans, can reduce Aβ load and promote cognitive improvement without increasing vascular microbleeds compared to other Aβ antibody studies [3]. In 2021, Fang et al [15] reported a novel recombinant chimeric 12×(Aβ1-15-Th) antigen targeting the pathological confirmation of Aβ oligomer for AD treatment. They tested the immunogenicity of the chimeric vaccine in C57/BL6 mice and demonstrated its efficacy in AD mice.…”

“…They tested the immunogenicity of the chimeric vaccine in C57/BL6 mice and demonstrated its efficacy in AD mice. The results showed that the chimeric vaccine showed a noticeable neuroprotective effect by reducing the levels of soluble Aβ oligomers and soluble Aβ in the brain, suggesting that the chimeric vaccine is a good candidate for AD prevention [15]. ABvac40 is an active vaccine against the C-terminal end of Aβ40, and an ongoing Phase II clinical trial is needed to explore the clinical efficacy of ABvac40 [30].…”