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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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Autores principales: Liu, Dong-qun, Lu, Shuai, Zhang, Lun, Huang, Ya-ru, Ji, Mei, Sun, Xiao-ying, Liu, Xiao-ge, Liu, Rui-tian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563250/
https://www.ncbi.nlm.nih.gov/pubmed/32630299
http://dx.doi.org/10.3390/vaccines8030351
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author Liu, Dong-qun
Lu, Shuai
Zhang, Lun
Huang, Ya-ru
Ji, Mei
Sun, Xiao-ying
Liu, Xiao-ge
Liu, Rui-tian
author_facet Liu, Dong-qun
Lu, Shuai
Zhang, Lun
Huang, Ya-ru
Ji, Mei
Sun, Xiao-ying
Liu, Xiao-ge
Liu, Rui-tian
author_sort Liu, Dong-qun
collection PubMed
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 pubmed-75632502020-10-27 Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer’s Disease Transgenic Mice Liu, Dong-qun Lu, Shuai Zhang, Lun Huang, Ya-ru Ji, Mei Sun, Xiao-ying Liu, Xiao-ge Liu, Rui-tian Vaccines (Basel) Article 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. MDPI 2020-07-01 /pmc/articles/PMC7563250/ /pubmed/32630299 http://dx.doi.org/10.3390/vaccines8030351 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Dong-qun
Lu, Shuai
Zhang, Lun
Huang, Ya-ru
Ji, Mei
Sun, Xiao-ying
Liu, Xiao-ge
Liu, Rui-tian
Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer’s Disease Transgenic Mice
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563250/
https://www.ncbi.nlm.nih.gov/pubmed/32630299
http://dx.doi.org/10.3390/vaccines8030351
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