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

ABSTRACT: BACKGROUND:Active immunotherapy targeting amyloid-? (A?) 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-A? antibodies while avoiding the activation of T cells specific to A?. RESULTS:An untagged A?1-6 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 A?1-6 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 A?1-6 chimeric soluble protein could induce the strongest A?-specific humoral immune responses without activation of harmful A?-specific T cells in mice. CONCLUSIONS:The untagged A?1-6 chimeric protein vaccine is safe and highly immunogenic. Further research will determine the efficacy in cognitive improvement and disease progression delay.

SUBMITTER: Yang P

PROVIDER: S-EPMC6373079 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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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.

Yang Ping P Guo Yongqing Y Sun Yao Y Yu Bin B Zhang Haihong H Wu Jiaxin J Yu Xianghui X Wu Hui H Kong Wei W

BMC immunology 20190212 1

<h4>Background</h4>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.<h4>Results</h4>An untagged Aβ1-6 chimeric protein vaccine against AD based on norovirus (NoV) P particle was expressed in Escherichia coli and obtained by sequential chromatogr ...[more]

PMID: 30755174

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Project description:UnlabelledThere is currently no licensed vaccine for noroviruses, and development is hindered, in part, by an incomplete understanding of the host adaptive immune response to these highly heterogeneous viruses and rapid GII.4 norovirus molecular evolution. Emergence of a new predominant GII.4 norovirus strain occurs every 2 to 4 years. To address the problem of GII.4 antigenic variation, we tested the hypothesis that chimeric virus-like particle (VLP)-based vaccine platforms, which incorporate antigenic determinants from multiple strains into a single genetic background, will elicit a broader immune response against contemporary and emergent strains. Here, we compare the immune response generated by chimeric VLPs to that of parental strains and a multivalent VLP cocktail. Results demonstrate that chimeric VLPs induce a more broadly cross-blocking immune response than single parental VLPs and a similar response to a multivalent GII.4 VLP cocktail. Furthermore, we show that incorporating epitope site A alone from one strain into the background of another is sufficient to induce a blockade response against the strain donating epitope site A. This suggests a mechanism by which population-wide surveillance of mutations in a single epitope could be used to evaluate antigenic changes in order to identify potential emergent strains and quickly reformulate vaccines against future epidemic strains as they emerge in human populations.ImportanceNoroviruses are gastrointestinal pathogens that infect an estimated 21 million people per year in the United States alone. GII.4 noroviruses account for >70% of all outbreaks, making them the most clinically important genotype. GII.4 noroviruses undergo a pattern of epochal evolution, resulting in the emergence of new strains with altered antigenicity over time, complicating vaccine design. This work is relevant to norovirus vaccine design as it demonstrates the potential for development of a chimeric VLP-based vaccine platform that may broaden the protective response against multiple GII.4 strains and proposes a potential reformulation strategy to control newly emergent strains in the human population.

Dataset Information

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

Publications

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

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