title: Anti-Aβ antibodies induced by Aβ-HBc virus-like particles prevent Aβ aggregation and protect PC12 cells against toxicity of Aβ1-40.
abstract: β-Amyloid peptide (Aβ) immunization is regarded as the most promising therapy to Alzheimer' s disease. The full length Aβ as antigen might induce meningoencepholontis adverse effect since the middle and C-terminal fragments of Aβ contain T cell epitopes. While N-terminal fragment of Aβ, containing B cell epitope, has weak or no immunogenicity. To improve the immunogenicity, we used HBV core antigen as carrier to make fusion protein containing 2 Aβ1-15. The fusion protein was expressed in Escherichia coli harboring the recombinant plasmid pET/c-2Aβ15-c. Transmission electron microscope (TEM) showed that fusion protein could form virus-like particles (VLPs). After 7-weeks immunization with Aβ-HBc VLPs through subcutaneous injection, the titer of anti-Aβ antibody in sera of BALB/c mice reached up to 10(5), higher than Aβ peptide immunization. Aβ-HBc VLPs immunization did not elicit Aβ-specific T cell proliferation. The main isotypes of antibody in mice immunized with Aβ-HBc VLPs were IgG1 and IgG2b, while isotype in mice immunized with Aβ1-42 was IgG2a. When the antisera from mice immunized with Aβ-HBc VLPs were co-incubated for 1 week at 37°C with Aβ, fibers of aggregated Aβ was reduced or diminished. The antibodies also prevented PC12 cells from injury by toxicity of Aβ. In conclusion, recombinant c-2Aβ15-c gene can be expressed in E. coli. The expressed protein could form VLPs and has strong immunogenicity. The antisera prevented Aβ fiber formation and protected the PC12 cells against toxicity of Aβ. This study lays the foundation for the experimental study of AD gene engineering vaccine.
authors.affiliation: Department of Human Anatomy and Histoembryology, School of Medicine, Xi'an Jiaotong University, 76(#) West Yanta Road, Xi'an, Shaanxi 710061, People's Republic of China. fenggaifeng@163.com
authors.forename: Gaifeng
authors.initials: G
authors.lastname: Feng
authors.forename: Weixi
authors.initials: W
authors.lastname: Wang
authors.forename: Yihua
authors.initials: Y
authors.lastname: Qian
authors.forename: Hui
authors.initials: H
authors.lastname: Jin
mesh_terms: D023582:Alzheimer Vaccines / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D005260:Female; D005818:Genetic Engineering / Q000379:methods*; D016174:Hepacivirus; D051379:Mice; D008807:Mice, Inbred BALB C; D016716:PC12 Cells; D010446:Peptide Fragments / Q000276:immunology* / Q000633:toxicity; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D058425:Vaccines, Virus-Like Particle; C078592:amyloid beta-protein (1-40)
keywords: Immunotherapy; Virus-like particles (VLPs); β-Amyloid peptide (Aβ)