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Active immunization with norovirus P particle-based amyloid-β chimeric protein vaccine induces high titers of anti-Aβ antibodies in mice

BACKGROUND: Active immunotherapy targeting amyloid-β (Aβ) is a promising treatment for Alzheimer’s disease (AD). Numerous preclinical studies and clinical trials demonstrated that a safe and effective AD vaccine should induce high titers of anti-Aβ antibodies while avoiding the activation of T cells...

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Autores principales: Yang, Ping, Guo, Yongqing, Sun, Yao, Yu, Bin, Zhang, Haihong, Wu, Jiaxin, Yu, Xianghui, Wu, Hui, Kong, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373079/
https://www.ncbi.nlm.nih.gov/pubmed/30755174
http://dx.doi.org/10.1186/s12865-019-0289-9
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author Yang, Ping
Guo, Yongqing
Sun, Yao
Yu, Bin
Zhang, Haihong
Wu, Jiaxin
Yu, Xianghui
Wu, Hui
Kong, Wei
author_facet Yang, Ping
Guo, Yongqing
Sun, Yao
Yu, Bin
Zhang, Haihong
Wu, Jiaxin
Yu, Xianghui
Wu, Hui
Kong, Wei
author_sort Yang, Ping
collection PubMed
description BACKGROUND: Active immunotherapy targeting amyloid-β (Aβ) is a promising treatment for Alzheimer’s disease (AD). Numerous preclinical studies and clinical trials demonstrated that a safe and effective AD vaccine should induce high titers of anti-Aβ antibodies while avoiding the activation of T cells specific to Aβ. RESULTS: An untagged Aβ1–6 chimeric protein vaccine against AD based on norovirus (NoV) P particle was expressed in Escherichia coli and obtained by sequential chromatography. Analysis of protein characteristics showed that the untagged Aβ1–6 chimeric protein expressed in soluble form exhibited the highest particle homogeneity, with highest purity and minimal host cell protein (HCP) and residual DNA content. Importantly, the untagged Aβ1–6 chimeric soluble protein could induce the strongest Aβ-specific humoral immune responses without activation of harmful Aβ-specific T cells in mice. CONCLUSIONS: The untagged Aβ1–6 chimeric protein vaccine is safe and highly immunogenic. Further research will determine the efficacy in cognitive improvement and disease progression delay. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12865-019-0289-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-63730792019-02-25 Active immunization with norovirus P particle-based amyloid-β chimeric protein vaccine induces high titers of anti-Aβ antibodies in mice Yang, Ping Guo, Yongqing Sun, Yao Yu, Bin Zhang, Haihong Wu, Jiaxin Yu, Xianghui Wu, Hui Kong, Wei BMC Immunol Research Article BACKGROUND: Active immunotherapy targeting amyloid-β (Aβ) is a promising treatment for Alzheimer’s disease (AD). Numerous preclinical studies and clinical trials demonstrated that a safe and effective AD vaccine should induce high titers of anti-Aβ antibodies while avoiding the activation of T cells specific to Aβ. RESULTS: An untagged Aβ1–6 chimeric protein vaccine against AD based on norovirus (NoV) P particle was expressed in Escherichia coli and obtained by sequential chromatography. Analysis of protein characteristics showed that the untagged Aβ1–6 chimeric protein expressed in soluble form exhibited the highest particle homogeneity, with highest purity and minimal host cell protein (HCP) and residual DNA content. Importantly, the untagged Aβ1–6 chimeric soluble protein could induce the strongest Aβ-specific humoral immune responses without activation of harmful Aβ-specific T cells in mice. CONCLUSIONS: The untagged Aβ1–6 chimeric protein vaccine is safe and highly immunogenic. Further research will determine the efficacy in cognitive improvement and disease progression delay. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12865-019-0289-9) contains supplementary material, which is available to authorized users. BioMed Central 2019-02-12 /pmc/articles/PMC6373079/ /pubmed/30755174 http://dx.doi.org/10.1186/s12865-019-0289-9 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Yang, Ping
Guo, Yongqing
Sun, Yao
Yu, Bin
Zhang, Haihong
Wu, Jiaxin
Yu, Xianghui
Wu, Hui
Kong, Wei
Active immunization with norovirus P particle-based amyloid-β chimeric protein vaccine induces high titers of anti-Aβ antibodies in mice
title Active immunization with norovirus P particle-based amyloid-β chimeric protein vaccine induces high titers of anti-Aβ antibodies in mice
title_full Active immunization with norovirus P particle-based amyloid-β chimeric protein vaccine induces high titers of anti-Aβ antibodies in mice
title_fullStr Active immunization with norovirus P particle-based amyloid-β chimeric protein vaccine induces high titers of anti-Aβ antibodies in mice
title_full_unstemmed Active immunization with norovirus P particle-based amyloid-β chimeric protein vaccine induces high titers of anti-Aβ antibodies in mice
title_short Active immunization with norovirus P particle-based amyloid-β chimeric protein vaccine induces high titers of anti-Aβ antibodies in mice
title_sort active immunization with norovirus p particle-based amyloid-β chimeric protein vaccine induces high titers of anti-aβ antibodies in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373079/
https://www.ncbi.nlm.nih.gov/pubmed/30755174
http://dx.doi.org/10.1186/s12865-019-0289-9
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