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BMC Immunol. 2019 Feb 12;20(1):9. doi: 10.1186/s12865-019-0289-9.

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

Yang P1, Guo Y1, Sun Y1, Yu B1,2, Zhang H1,2, Wu J1,2, Yu X1,2, Wu H3,4, Kong W5,6.

Author information

1
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, China.
2
Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, China.
3
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, China. topwuhui@jlu.edu.cn.
4
Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, China. topwuhui@jlu.edu.cn.
5
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, China. weikong@jlu.edu.cn.
6
Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, China. weikong@jlu.edu.cn.

Abstract

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.

KEYWORDS:

Active immunization; Alzheimer’s disease; Amyloid-β; Norovirus P particle; Protein vaccine

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