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

Active vaccination against amyloid beta (A beta 42) is considered a potential therapeutic approach for Alzheimer's disease (AD). However, immunization with synthetic human A beta 1-42 has resulted in meningoencephalitis in 6% of patients and generated only low-titer anti-A beta 42 antibodies. In order to develop a safe and effective vaccine against Alzheimer's disease, the A beta 1-6 peptide was used as the novel immunogen and Norovirus P particles as the vaccine platform in this study. By inserting and presenting A beta 1-6 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 A beta 42 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 A beta 42 antibody production, and chimeric P particles may be developed as an effective therapy for AD. (C) 2015 Elsevier B.V. All rights reserved.