Specific humoral immune responses in rhesus monkeys vaccinated with the Alzheimer's disease-associated beta-amyloid 1-15 peptide vaccine / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by overproduction of beta-amyloid (Abeta), with the subsequent pathologic deposition of Abeta which is important for memory and cognition. Recent studies showed murine models of AD and AD patients inoculated with Abeta(1-42) peptide vaccine had a halted or delayed pathological progression of AD. Unfortunately, the clinical phase IIa trial of Abeta(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 Abeta(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 Abeta(1-15) peptide vaccine.</p><p><b>METHODS</b>Five male adult rhesus monkeys were injected intramuscularly with Abeta(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 Abeta(1-42) in serum was measured by Enzyme-linked Immunosorbent Assay (ELISA). The specificity of the antibody against Abeta(1-42) was determined by Western blot. The Abeta plaques in Tg2576 transgenic mouse brain were stained with the antiserum using immunohistochemistry method.</p><p><b>RESULTS</b>At the eighth week after the vaccination, antibody against Abeta(1-42) began to develop significantly in serum. The titers of the antibody increased following vaccine boosted and reached 13840 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 Abeta(1-42) showed high specificity. The Abeta plaques in Tg2576 transgenic mouse brain were labeled with the antiserum.</p><p><b>CONCLUSION</b>Abeta(1-15) vaccine can induce vigorously specific humoral immune responses in adult rhesus monkey.</p>