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

Ping Yang,
Yongqing Guo,
Yao Sun,
Bin Yu,
Haihong Zhang,
Jiaxin Wu,
Xianghui Yu,
Hui WuEmail author View ORCID ID profile and
Wei KongEmail author

BMC Immunology201920:9

https://doi.org/10.1186/s12865-019-0289-9

Received: 26 November 2018
Accepted: 30 January 2019
Published: 12 February 2019

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.