Immunol Lett. 2015 Nov;168(1):22-30. doi: 10.1016/j.imlet.2015.09.002. Epub 2015 Sep 5.

Norovirus P particle: An excellent vaccine

platform for antibody production against
Alzheimer's disease.
Fu L1, Li Y2, Hu Y2, Yu B1, Zhang H1, Wu J1, Wu H3, Yu X4, Kong W5.

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Abstract
Active vaccination against amyloid (A42) is considered a potential therapeutic approach for
Alzheimer's disease (AD). However, immunization with synthetic human A1-42 has resulted in
meningoencephalitis in 6% of patients and generated only low-titer anti-A42 antibodies. In
order to develop a safe and effective vaccine against Alzheimer's disease, the A1-6 peptide was
used as the novel immunogen and Norovirus P particles as the vaccine platform in this study. By
inserting and presenting A1-6 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 A42 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 A42 antibody production, and chimeric P particles may be developed as an
effective therapy for AD.