科研之友
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摘要
Amyloid-beta (A beta) plaque accumulation in the brain is one of the hallmarks of Alzheimer's disease (AD). Immunotherapy against A beta was considered a potential strategy for reducing the All load in the brain. However, none of the A beta immunotherapies have produced clinically meaningful results to date, due to poor safety or lack of efficacy. Thus, we aimed to design a safe and effective vaccine against AD. In this study, we used bacterium-like particles (BLPs) as carriers and different copy numbers of the A beta 1-6 peptide as epitopes to design four All active immunization vaccines. The epitopes containing different copy numbers of the A beta 1-6 peptide were specifically loaded on the surface of BLPs via fusion with a peptidoglycan anchoring domain. These four BLP-based A beta vaccines successfully induced high levels of A beta 42-specific antibodies in mice. However, none of the vaccines induced a T-cell-mediated immune response. Importantly, the antibodies induced by these four vaccines were effective in blocking A beta 42 oligomer toxicity at the cellular level. Among the four vaccines, 6copy-A beta 1-6-PA-BLP was the most effective in inducing AP-specific antibodies, indicating that a suitable epitope copy number is critical for high immunogenicity of the BLP-based vaccine. Furthermore, high levels of serum AP-specific antibodies could still be detected 3 months after the final administration of 6copy-A beta 1-6-PA-BLP. Thus, 6copy-A beta 1-6 -PA-BLP may be a potential therapeutic treatment for AD.
