Norovirus P particle: an excellent vaccine platform for antibody production against Alzheimer's disease.

Abstract

Active vaccination against amyloid β (Aβ42) is considered a potential therapeutic approach for Alzheimer's disease (AD). However, immunization with synthetic human Aβ1-42 has resulted in meningoencephalitis in 6% of patients and generated only low-titer anti-Aβ42 antibodies. In order to develop a safe and effective vaccine against Alzheimer's disease, the Aβ1-6 peptide was used as the novel immunogen and Norovirus P particles as the vaccine platform in this study. By inserting and presenting Aβ1-6 on the outermost surface of the P particle, we showed that the chimeric P particle-based AD protein vaccine could elicit a strong immune response, inducing highly specific antibody titers against Aβ42 without causing T-cell activation. Furthermore, antibodies induced by the AD protein vaccines were demonstrated to be effective at the cellular level. In addition, we also compared the immunogenicity of the chimeric P particles with different insertional loci in the loop structure domain and demonstrated that insertion of the antigen into all three loops of the P particle at the same time could significantly improve immune responses to the vaccine. In conclusion, the Norovirus P particle is an excellent vaccine platform for stimulating Aβ42 antibody production, and chimeric P particles may be developed as an effective therapy for AD.

• Authors: Lu Fu, Yingnan Li, Yue Hu, Bin Yu, Haihong Zhang, Jiaxin Wu, Hui Wu, Xianghui Yu, Wei Kong
• Journal: Immunology letters (Immunol Lett) Vol. 168 Issue 1 Pg. 22-30 (Nov 2015) ISSN: 1879-0542 [Electronic] Netherlands
• PMID: 26349054 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Antibodies
• Peptide Fragments
• Vaccines
• amyloid beta-protein (1-42)
• amyloid beta-protein (1-6)

Topics

• Alzheimer Disease (immunology, prevention & control)
• Amino Acid Sequence
• Amyloid beta-Peptides (genetics, immunology)
• Animals
• Antibodies (blood, immunology)
• Antibody Formation (immunology)
• Blotting, Western
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Immunization
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Microscopy, Electron, Transmission
• Molecular Sequence Data
• Norovirus (genetics, immunology, ultrastructure)
• PC12 Cells
• Peptide Fragments (genetics, immunology)
• Rats
• Vaccines (administration & dosage, immunology)
• Virion (genetics, immunology, ultrastructure)