Lambracht-Washington Doris, Qu Bao-Xi, Fu Min, Eagar Todd N, Stüve Olaf, Rosenberg Roger N
Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9108, USA.
JAMA. 2009 Oct 28;302(16):1796-802. doi: 10.1001/jama.2009.1547.
DNA beta-amyloid(1-42) (Abeta42) trimer immunization was developed to produce specific T helper 2 cell (T(H)2)-type antibodies to provide an effective and safe therapy for Alzheimer disease (AD) by reducing elevated levels of Abeta42 peptide that occur in the brain of patients with AD.
To compare the immune response in wild-type mice after immunization with DNA Abeta42 trimer and Abeta42 peptide.
Wild-type mice received either 4 microg of DNA Abeta42 trimer immunization administered with gene gun (n = 8) or intraperitoneal injection of 100 microg of human Abeta42 peptide with the adjuvant Quil A (n = 8). Titers, epitope mapping, and isotypes of the Abeta42-specific antibodies were analyzed.
Antibody titers, mapping of binding sites (epitopes), isotype profiles of the Abeta42-specific antibodies, and T-cell activation.
DNA Abeta42 trimer immunization resulted in antibody titers with a mean of 15 microg per milliliter of plasma. The isotype profile of the antibodies differed markedly. A predominant IgG1 antibody response was found in the DNA-immunized mice, indicating a T(H)2 type of immune response (IgG1/IgG2a ratio of 10). The peptide-immunized mice showed a mixed T(H)1/T(H)2 immune response (IgG1/IgG2a ratio of 1) (P < .001). No increased T-cell proliferation was observed in the DNA-immunized mice (P = .03).
In this preliminary study in a wild-type mouse model, DNA Abeta42 trimer immunization protocol produced a T(H)2 immune response and appeared to have low potential to cause an inflammatory T-cell response.
研发了DNAβ-淀粉样蛋白（1-42）（Aβ42）三聚体免疫法，以产生特异性辅助性T2细胞（Th2）型抗体，通过降低阿尔茨海默病（AD）患者大脑中升高的Aβ42肽水平，为AD提供有效且安全的治疗方法。
比较野生型小鼠经DNA Aβ42三聚体和Aβ42肽免疫后的免疫反应。
野生型小鼠接受用基因枪给予的4μg DNA Aβ42三聚体免疫（n = 8）或腹腔注射100μg人Aβ42肽与佐剂Quil A（n = 8）。分析Aβ42特异性抗体的滴度、表位图谱和亚型。
抗体滴度、结合位点（表位）图谱、Aβ42特异性抗体的亚型谱以及T细胞活化情况。
DNA Aβ42三聚体免疫导致抗体滴度平均为每毫升血浆15μg。抗体的亚型谱有显著差异。在DNA免疫的小鼠中发现主要是IgG1抗体反应，表明是Th2型免疫反应（IgG1/IgG2a比值为10）。肽免疫的小鼠表现出混合的Th1/Th2免疫反应（IgG1/IgG2a比值为1）（P <.001）。在DNA免疫的小鼠中未观察到T细胞增殖增加（P =.03）。
在这个野生型小鼠模型的初步研究中，DNA Aβ42三聚体免疫方案产生了Th2免疫反应，并且似乎引起炎性T细胞反应的可能性较低。
