The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Vaccine. 2011 May 23;29(23):4043-50. doi: 10.1016/j.vaccine.2011.03.033. Epub 2011 Apr 5.
Active vaccination with amyloid beta peptide (Aβ) to induce beneficial antibodies was found to be effective in mouse models of Alzheimer's disease (AD), but human vaccination trials led to adverse effects, apparently caused by exuberant T-cell reactivity. Here, we sought to develop a safer active vaccine for AD with reduced T-cell activation. We treated a mouse model of AD carrying the HLA-DR DRB1*1501 allele, with the Aβ B-cell epitope (Aβ 1-15) conjugated to the self-HSP60 peptide p458. Immunization with the conjugate led to the induction of Aβ-specific antibodies associated with a significant reduction of cerebral amyloid burden and of the accompanying inflammatory response in the brain; only a mild T-cell response specific to the HSP peptide but not to the Aβ peptide was found. This type of vaccination, evoking a gradual increase in antibody titers accompanied by a mild T-cell response is likely due to the unique adjuvant and T-cell stimulating properties of the self-HSP peptide used in the conjugate and might provide a safer approach to effective AD vaccination.
用淀粉样β肽（Aβ）进行主动免疫接种以诱导有益的抗体已被证明在阿尔茨海默病（AD）的小鼠模型中是有效的，但人类疫苗接种试验导致了不良反应，显然是由过度的 T 细胞反应引起的。在这里，我们试图开发一种更安全的 AD 主动疫苗，减少 T 细胞的激活。我们用淀粉样蛋白β的 B 细胞表位（Aβ 1-15）与自身 HSP60 肽 p458 偶联物治疗携带 HLA-DR DRB1*1501 等位基因的 AD 小鼠模型。用该偶联物免疫接种可诱导与大脑淀粉样蛋白负荷显著降低和伴随的大脑炎症反应相关的 Aβ特异性抗体；仅发现针对 HSP 肽而非 Aβ肽的轻度 T 细胞反应。这种类型的疫苗接种，引起抗体滴度的逐渐增加，同时伴有轻度的 T 细胞反应，可能是由于偶联物中使用的自身 HSP 肽具有独特的佐剂和 T 细胞刺激特性，可能为有效的 AD 疫苗接种提供更安全的方法。
