Specific humoral immune responses in rhesus monkeys vaccinated with the Alzheimer's disease-associated beta-amyloid 1-15 peptide vaccine
Li, S-bing.; Wang, H-qiao.; Lin, X.; Xu, J.; Xie, Y.; Yuan, Q-fang.; Yao, Z-bin.
Chinese Medical Journal 118(8): 660-664
2005
ISSN/ISBN: 0366-6999 PMID: 15899121 Document Number: 588889
Background Alzheimer' s disease( AD) is a neurodegenerative disorder characterized by overproduction of beta-amylold (A beta), with the subsequent patbologic deposition of A beta which is important for memory and cognition. Recent studies showed murine models of AD and AD patients inoculated with A beta, peptide vaccine had a halted or delayed pathological progression of AD. Unfortunately, the clinical phase IIa. trial of A beta(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 A beta(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 A beta(1-15) peptide vaccine.Methods Five male adult rhesus monkeys were injected intramuscularly with A beta(1-15) peptide vaccine at baseline and at weeks 2, 6, 10, 14, 18 and 22. The titers and IgG isotypes of the antibody against A beta(1-42) in serum was measured by Enzyme-linked Immunosorbent Assay (ELISA). The specificity of the antibody against A beta(1-42) was determined by Western blot. The A beta plaques in Tg2576 transgenic mouse brain were stained with the antiserunt using immunohistochemistry method. Results At the eighth week after the vaccination, antibody against A beta(1-42) began to develop significantly in serum. The titers 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 A beta(1-42) showed high specificity. The A beta plaques in Tg2576 transgenic mouse brain were labeled with the antiserum.Conclusion A beta(1-15) vaccine can induce vigorously specific Immoral immune responses in adult rhesus monkey.