Anti-Aβ antibodies induced by Aβ-HBc virus-like particles prevent Aβ aggregation and protect PC12 cells against toxicity of Aβ1-40

beta-Amyloid peptide (A beta) immunization is regarded as the most promising therapy to Alzheimer' s disease. The full length A beta as antigen might induce meningoencepholontis adverse effect since the middle and C-terminal fragments of A beta contain T cell epitopes. While N-terminal fragment of A beta, 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 A beta(1-15). The fusion protein was expressed in Escherichia coli harboring the recombinant plasmid pET/c-2A beta(15)-c. Transmission electron microscope (TEM) showed that fusion protein could form virus-like particles (VLPs). After 7-weeks immunization with A beta-HBc VLPs through subcutaneous injection, the titer of anti-A beta antibody in sera of BALB/c mice reached up to 105, higher than A beta peptide immunization. A beta-HBc VLPs immunization did not elicit A beta-specific T cell proliferation. The main isotypes of antibody in mice immunized with A beta-HBc VLPs were IgG1 and IgG2b, while isotype in mice immunized with A beta(1-42) was IgG2a. When the antisera from mice immunized with A beta-HBc VLPs were co-incubated for 1 week at 37 degrees C with A beta, fibers of aggregated A beta was reduced or diminished. The antibodies also prevented PC12 cells from injury by toxicity of A beta. In conclusion, recombinant c-2A beta(15)-c gene can be expressed in E. coli. The expressed protein could form VLPs and has strong immunogenicity. The antisera prevented A beta fiber formation and protected the PC12 cells against toxicity of A beta. This study lays the foundation for the experimental study of AD gene engineering vaccine. (c) 2013 Elsevier B.V. All rights reserved.