Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer's Disease Transgenic Mice

Immunotherapy focusing on reducing the amyloid-beta (A beta) burden is a promising treatment strategy for Alzheimer's disease (AD). Many clinical studies on AD immunotherapies have failed due to low safety and efficacy, calling for a highly potent AD vaccine which induces sufficient antibody titer while avoiding side effects. Here, we designed a yeast-based vaccine Y-5A15 comprising five copies of A beta 1-15 displayed on the surface of yeast cell wall, and we subcutaneously immunized APP/PS1 mice three times. Our results demonstrated that the Y-5A15 remarkably enhanced the A beta epitope immunogenicity and elicited high antibody titers against A beta in AD mice. Importantly, Y-5A15 vaccination successfully reduced A beta levels, plaque burden and glial activation, rescued synaptic deficits and significantly ameliorated memory and cognitive decline in APP/PS1 transgenic mice, suggesting that the yeast-based A beta epitope vaccine has a promising potency for the treatment of AD.