Aβ-HBc virus-like particles immunization without additional adjuvant ameliorates the learning and memory and reduces Aβ deposit in PDAPP mice

Abstract

β-Amyloid peptide (Aβ) immunization is regarded as a promising therapy to Alzheimer's disease. The full length Aβ as antigen might induce meningoencephalitis 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, in the previous study, we used HBv core antigen as carrier to make fusion protein containing 2 Aβ1-15. The fusion protein could form virus-like particles (VLPs) and had strong immunogenicity. The antisera prevented Aβ fiber formation and protected the PC12 cells against toxicity of Aβ. In the present study, we immunized 12-month old AD transgenic mice, PDAPP mice, to observe the therapeutic effect of immunization on behaviour and pathology. During immunization, the titer of anti-Aβ antibody reached to nearly 1:10(6) after 4th inoculation, and then maintained that level to the end of the experiment. After 6-month immunization, the behavioral changes of mice were tested by Morris Water Maze (MWM). The escape latency of immunized mice was shorter than control, and these mice entered platform quadrant more times. Immunohistochemistry results showed that Aβ-HBc VLPs immunized mice had less amyloid deposit with less microglia in cortex and hippocampus. In conclusion, Aβ-HBc VLPs ameliorated the learning and memory and reduced cerebral Aβ deposit in PDAPP mice.

Keywords: Alzheimer's disease; Immunotherapy; Virus-like particles (VLPs); β-Amyloid peptide (Aβ).