Li Shao-bing, Wang Hua-qiao, Lin Xian, Xu Jie, Xie Yao, Yuan Qun-fang, Yao Zhi-bin
Department of Anatomy, Zhongshan Medical College, Sun Yat-sen University, Guangzhou 510080, China.
Chin Med J (Engl). 2005 Apr 20;118(8):660-4.
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.
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.
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 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 Abeta(1-42) showed high specificity. The Abeta plaques in Tg2576 transgenic mouse brain were labeled with the antiserum.
Abeta(1-15) vaccine can induce vigorously specific humoral immune responses in adult rhesus monkey.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是β-淀粉样蛋白（Aβ）过度产生，随后Aβ发生病理性沉积，这对记忆和认知很重要。最近的研究表明，接种Aβ（1-42）肽疫苗的AD小鼠模型和AD患者的AD病理进展停滞或延迟。不幸的是，Aβ（1-42）肽疫苗（AN1792）的临床IIa期试验由于18名接种疫苗的患者出现脑膜脑炎而提前终止。用Aβ（1-15）肽疫苗接种BALB/c或Tg2576转基因小鼠是安全的，免疫效果令人满意。本研究进一步表征了Aβ（1-15）肽疫苗诱导的成年恒河猴的特异性体液免疫反应。
五只成年雄性恒河猴在基线时以及第2、6、10、14、18和22周肌肉注射Aβ（1-15）肽疫苗。通过酶联免疫吸附测定（ELISA）测量血清中抗Aβ（1-42）抗体的滴度和IgG亚型。通过蛋白质印迹法确定抗Aβ（1-42）抗体的特异性。使用免疫组织化学方法用抗血清对Tg2576转基因小鼠脑内的Aβ斑块进行染色。
接种疫苗后第八周，血清中抗Aβ（1-42）抗体开始显著产生。抗体滴度在疫苗加强后升高，在第24周达到1:3840，接种终止后下降。IgG1在抗血清池中占最高水平。抗Aβ（1-42）抗体具有高度特异性。Tg2576转基因小鼠脑内的Aβ斑块用抗血清标记。
Aβ（1-15）疫苗可在成年恒河猴中强烈诱导特异性体液免疫反应。
