Norovirus P particle: an excellent vaccine platform for antibody production against Alzheimer's disease.
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.
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Lu
L
Fu
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
Yingnan
Y
Li
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
Yue
Y
Hu
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Bin
B
Yu
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Haihong
H
Zhang
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Jiaxin
J
Wu
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China. Electronic address: topwuhui@jlu.edu.cn.
Hui
H
Wu
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China. Electronic address: xianghui@jlu.edu.cn.
Xianghui
X
Yu
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China. Electronic address: weikong@jlu.edu.cn.
Wei
W
Kong
D000544:Alzheimer Disease / Q000276:immunology* / Q000517:prevention & control; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007114:Immunization; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D029322:Norovirus / Q000235:genetics / Q000276:immunology* / Q000648:ultrastructure; D016716:PC12 Cells; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D051381:Rats; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014771:Virion / Q000235:genetics / Q000276:immunology* / Q000648:ultrastructure
D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; D014612:Vaccines; C075222:amyloid beta-protein (1-42); C505239:amyloid beta-protein (1-6)
Alzheimer’s disease; Amyloid β1–6; Norovirus; P particle