Specific humoral immune responses in rhesus monkeys vaccinated with the Alzheimer's disease-associated β-amyloid 1-15 peptide vaccine

摘要

Background Alzheimer's disease (AD) is a neurodegenerative disorder characterized by overproduction of β-amyloid (Aβ) , with the subsequent pathologic deposition of Aβ which is important for memory and cognition. Recent studies showed murine models of AD and AD patients inoculated with Aβ_(1-42) peptide vaccine had a halted or delayed pathological progression of AD. Unfortunately, the clinical phase Ⅱ_a trial of Aβ_(1-42) peptide vaccine (AN1792) was halted prematurely because of episodes of menigoencephalitis in 18 of the vaccinated patients. The vaccination of BALB/c or Tg2576 transgenic mouse with Aβ_(1-15) peptide vaccine is safe and the immune effects are satisfactory. This study further characterizes the specific humoral immune responses in adult rhesus monkeys induced by Aβ_(1-15) peptide vaccine. Methods Five male adult rhesus monkeys were injected intramuscularly with Aβ_(1-15) peptide vaccine at baseline and at weeks 2, 6, 10, 14, 18 and 22. The liters and IgG isotypes of the antibody against Aβ_(1-42) in serum was measured by Enzyme-linked Immunosorbent Assay (ELISA). The specificity of the antibody against Aβ_(1-42) was determined by Western blot. The Aβ plaques in Tg2576 transgenic mouse brain were stained with the antiserum using immunohistochemistry method. Results At the eighth week after the vaccination, antibody against Aβ_(1-42) began to develop significantly in serum. The tilers of the antibody increased following vaccine boosted and reached 1:3840 at the twenty-fourth week, then decreased after the termination of inoculation. The IgG1 was accounted for the highest level in the antiserum pool. The antibody against Aβ_(1-42) showed high specificity. The Aβ plaques in Tg2576 transgenic mouse brain were labeled with the antiserum. Conclusion Aβ_(1-15) vaccine can induce vigorously specific humoral immune responses in adult rhesus monkey.