The development of therapeutic nanovaccine that elicits anti‐Aβ antibodies and Aβ‐specific regulatory T cells for the treatment of Alzheimer’s disease.

Abstract Background Alzheimer’s disease (AD) is a multi‐factorial cognitive disorder with complex pathogenesis including the accumulation of beta‐amyloid (Aβ) plaque and neuroinflammation. In previous studies, active immunotherapy injecting Aβ peptide as an antigen achieved the prophylaxis of Aβ accumulation by generating anti‐Aβ antibodies. Otherwise, the adoptive transfer of regulatory T (Treg) cells attenuated neuroinflammation by secreting anti‐inflammatory cytokines in the AD brain. To combine both approaches and improve the therapeutic efficacy against AD, we developed a nanovaccine that presents Aβ peptides as antigen and simultaneously induce the differentiation of naive T cells into Aβ‐specific Treg cells. Method A lipid nanoparticle loaded with Aβ peptides and rapamycin (LNP‐R/Aβ) was intradermally injected once a week for five weeks into a transgenic AD mouse model, 5XFAD. The…