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A Therapeutic Nanovaccine that Generates Anti-amyloid Antibodies and Amyloid-specific Regulatory T cells for Alzheimer's Disease
Mungyo Jung 1, Songmin Lee 2, Sohui Park 2, Jihye Hong 3, Cheesue Kim 1, Illhwan Cho 2, Hee Su Sohn 1, Kyunghwan Kim 2, In Wook Park 2, Soljee Yoon 2 4, Sungpil Kwon 1, Jisu Shin 2, Donghee Lee 2, Mikyung Kang 3, Seokhyung Go 3, Sangjun Moon 1, Yeonseok Chung 5, YoungSoo Kim 2 4 6, Byung-Soo Kim 1 3 7
...Here, we developed a nanovaccine composed of lipid nanoparticles loaded with Aβ peptides and rapamycin, which targets multiple pathophysiological mechanisms, exhibits the combined effects of anti-Aβ antibody therapy and adoptive Aβ-specific Treg cell transfer, and can overcome the limitations of current immunotherapy approaches for AD. Nanovaccines effectively deliver rapamycin and Aβ peptides to dendritic cells, produce both anti-Aβ antibodies and Aβ-specific Treg cells, remove Aβ plaques in the brain, alleviate neuroinflammation, prevent Th1 cell-mediated excessive immune responses, and inhibit cognitive impairment in mice. Nanovaccines show higher efficacy in cognitive recovery than an Aβ vaccine. Unlike anti-Aβ mAb therapy and adoptive Treg cell transfer, both of which require complicated and costly manufacturing processes, nanovaccines are easy-to-prepare and cost-effective. Nanovaccines could represent a novel treatment option for AD.