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

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.