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 (Aβ) 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...

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Main Authors: Dong-qun Liu, Shuai Lu, Lun Zhang, Ya-ru Huang, Mei Ji, Xiao-ying Sun, Xiao-ge Liu, Rui-tian Liu
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/8/3/351
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author Dong-qun Liu
Shuai Lu
Lun Zhang
Ya-ru Huang
Mei Ji
Xiao-ying Sun
Xiao-ge Liu
Rui-tian Liu
author_facet Dong-qun Liu
Shuai Lu
Lun Zhang
Ya-ru Huang
Mei Ji
Xiao-ying Sun
Xiao-ge Liu
Rui-tian Liu
author_sort Dong-qun Liu
collection DOAJ
description Immunotherapy focusing on reducing the amyloid-beta (Aβ) 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 Aβ1-15 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 Aβ epitope immunogenicity and elicited high antibody titers against Aβ in AD mice. Importantly, Y-5A15 vaccination successfully reduced Aβ 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 Aβ epitope vaccine has a promising potency for the treatment of AD.
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spelling doaj.art-13b7b46a031c4de59d1e6b3c2214995e2023-11-20T05:34:59ZengMDPI AGVaccines2076-393X2020-07-018335110.3390/vaccines8030351Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer’s Disease Transgenic MiceDong-qun Liu0Shuai Lu1Lun Zhang2Ya-ru Huang3Mei Ji4Xiao-ying Sun5Xiao-ge Liu6Rui-tian Liu7National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaImmunotherapy focusing on reducing the amyloid-beta (Aβ) 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 Aβ1-15 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 Aβ epitope immunogenicity and elicited high antibody titers against Aβ in AD mice. Importantly, Y-5A15 vaccination successfully reduced Aβ 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 Aβ epitope vaccine has a promising potency for the treatment of AD.https://www.mdpi.com/2076-393X/8/3/351Alzheimer’s diseasebeta-amyloidactive immunotherapyyeastvaccine
spellingShingle Dong-qun Liu
Shuai Lu
Lun Zhang
Ya-ru Huang
Mei Ji
Xiao-ying Sun
Xiao-ge Liu
Rui-tian Liu
Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer’s Disease Transgenic Mice
Vaccines
Alzheimer’s disease
beta-amyloid
active immunotherapy
yeast
vaccine
title Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer’s Disease Transgenic Mice
title_full Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer’s Disease Transgenic Mice
title_fullStr Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer’s Disease Transgenic Mice
title_full_unstemmed Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer’s Disease Transgenic Mice
title_short Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer’s Disease Transgenic Mice
title_sort yeast based aβ1 15 vaccine elicits strong immunogenicity and attenuates neuropathology and cognitive deficits in alzheimer s disease transgenic mice
topic Alzheimer’s disease
beta-amyloid
active immunotherapy
yeast
vaccine
url https://www.mdpi.com/2076-393X/8/3/351
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