Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783595448438620160 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7563250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liudongqun yeastbasedab115vaccineelicitsstrongimmunogenicityandattenuatesneuropathologyandcognitivedeficitsinalzheimersdiseasetransgenicmice AT lushuai yeastbasedab115vaccineelicitsstrongimmunogenicityandattenuatesneuropathologyandcognitivedeficitsinalzheimersdiseasetransgenicmice AT zhanglun yeastbasedab115vaccineelicitsstrongimmunogenicityandattenuatesneuropathologyandcognitivedeficitsinalzheimersdiseasetransgenicmice AT huangyaru yeastbasedab115vaccineelicitsstrongimmunogenicityandattenuatesneuropathologyandcognitivedeficitsinalzheimersdiseasetransgenicmice AT jimei yeastbasedab115vaccineelicitsstrongimmunogenicityandattenuatesneuropathologyandcognitivedeficitsinalzheimersdiseasetransgenicmice AT sunxiaoying yeastbasedab115vaccineelicitsstrongimmunogenicityandattenuatesneuropathologyandcognitivedeficitsinalzheimersdiseasetransgenicmice AT liuxiaoge yeastbasedab115vaccineelicitsstrongimmunogenicityandattenuatesneuropathologyandcognitivedeficitsinalzheimersdiseasetransgenicmice AT liuruitian yeastbasedab115vaccineelicitsstrongimmunogenicityandattenuatesneuropathologyandcognitivedeficitsinalzheimersdiseasetransgenicmice |