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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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Detalles Bibliográficos
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
Descripción
Sumario: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.