Spooner Edward T, Desai Roanak V, Mori Chica, Leverone Jodi F, Lemere Cynthia A
Center for Neurologic Diseases, Brigham & Woman's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115-5716, USA.
Vaccine. 2002 Dec 13;21(3-4):290-7. doi: 10.1016/s0264-410x(02)00464-4.
Previous studies have shown that in various mouse models of Alzheimer's disease (AD), amyloid beta-protein (Abeta) antibodies generated by Abeta peptide immunization resulted in the prevention of Abeta plaque formation in brains of young mice, decreased Abeta plaque burdens in older mice and improved cognition. The purpose of this study was to optimize Abeta immunization protocols for future trials in transgenic mouse models of AD. The timing and titers of Abeta antibody production, as well as epitope(s) and imunoglobulin isotypes, were compared between two different mouse strains (C57BL/6 and B6D2F1) and five treatment protocols: (1). chronic Abeta nasal administration, (2). repeated Abeta intraperitoneal (i.p.) injection, (3). one i.p. injection followed by chronic Abeta nasal administration, (4). chronic and concurrent Abeta nasal administration + Abeta i.p. injection, and (5). untreated controls. B6D2F1 mice generated Abeta antibodies earlier and in higher quantities than the C57BL/6 mice, indicating that B6D2F1 mice are more responsive to Abeta immunization. For both strains, mice that received the combination of Abeta nasal + Abeta i.p. injection showed the highest antibody titers. Epitope mapping experiments indicated that the mouse anti-Abeta antibodies recognize residues within Abeta1-15. Immunoglobulin isotyping demonstrated that the Abeta antibodies are of the Th-2 anti-inflammatory type, IgG1 and IgG2b, with a few IgM. Currently there is no effective therapy for Alzheimer's disease; thus if Abeta immunization proves effective, it would be a significant step in the prevention and/or treatment of this devastating disease.
先前的研究表明，在各种阿尔茨海默病（AD）小鼠模型中，由β淀粉样蛋白（Aβ）肽免疫产生的Aβ抗体可预防幼鼠大脑中Aβ斑块的形成，减少老年小鼠的Aβ斑块负担并改善认知。本研究的目的是优化Aβ免疫方案，以便在AD转基因小鼠模型中进行未来试验。比较了两种不同小鼠品系（C57BL/6和B6D2F1）和五种治疗方案之间Aβ抗体产生的时间和效价，以及表位和免疫球蛋白同种型：（1）. Aβ慢性鼻腔给药；（2）. 重复腹腔内（i.p.）注射Aβ；（3）. 一次i.p.注射后进行Aβ慢性鼻腔给药；（4）. Aβ慢性同时鼻腔给药 + Aβ i.p.注射；以及（5）. 未治疗的对照。B6D2F1小鼠比C57BL/6小鼠更早且更大量地产生Aβ抗体，表明B6D2F1小鼠对Aβ免疫更敏感。对于这两种品系，接受Aβ鼻腔 + Aβ i.p.注射组合的小鼠显示出最高的抗体效价。表位作图实验表明，小鼠抗Aβ抗体识别Aβ1-15内的残基。免疫球蛋白分型表明，Aβ抗体属于Th-2抗炎类型，即IgG1和IgG2b，还有少量IgM。目前尚无针对阿尔茨海默病的有效疗法；因此，如果Aβ免疫被证明有效，这将是预防和/或治疗这种毁灭性疾病的重要一步。
