title: Norovirus P particle-based active Aβ immunotherapy elicits sufficient immunogenicity and improves cognitive capacity in a mouse model of Alzheimer's disease.
abstract: Disease-modifying immunotherapies focusing on reducing amyloid-beta (Aβ) deposition are the main treatment for Alzheimer's disease (AD). However, none of the Aβ immunotherapies has produced clinically meaningful results to date. The main reason for this lack of efficacy is that the vaccine induces insufficiently high antibody titers, as it contains small B-cell epitope of Aβ to avoid Aβ42-specific T-cell activation. With the aim of generating a potent AD vaccine, we designed the protein PP-3copy-Aβ1-6-loop123, comprising three copies of Aβ1-6 inserted into three loops of a novel vaccine platform, the norovirus P particle, which could present Aβ at its surface and remarkably enhance the immunogenicity of the vaccine. We demonstrated that PP-3copy-Aβ1-6-loop123 was able to elicit high antibody titers against Aβ42, without causing T-cell activation, in AD mice regardless of their age. Importantly, PP-3copy-Aβ1-6-loop123 treatment successfully reduced amyloid deposition, rescued memory loss, and repaired hippocampus damage in AD mice. The Aβ antibodies induced by this active immunotherapy reacted with and disrupted aggregated Aβ, reducing its cellular toxicity. In addition, our results suggested PP-3copy-Aβ1-6-loop123 immunization could restore Aβ42 homeostasis in both the serum and brain. Thus, the P particle-based Aβ epitope vaccine is a sufficiently immunogenic and safe immunotherapeutic intervention for Alzheimer's disease.
authors.affiliation: 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.
authors.forename: Lu
authors.initials: L
authors.lastname: Fu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Yayuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Haihong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000523:psychology / Q000628:therapy; D023582:Alzheimer Vaccines / Q000737:chemistry / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D003071:Cognition; D004195:Disease Models, Animal; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D029322:Norovirus / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014771:Virion / Q000276:immunology
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides