McDevitt Hugh
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5204, USA.
Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2(Suppl 2):14627-30. doi: 10.1073/pnas.0405235101. Epub 2004 Oct 4.
Specific antigen vaccination by administration of the target antigen in aqueous solution has resulted in significant decreases of disease severity in animal models of experimental allergic encephalomyelitis, type I diabetes, and several forms of antigen-induced arthritis, even if administered after the initiation of symptoms. However, in experimental autoimmune encephalomyelitis (EAE) and type I diabetes in nonobese diabetic (NOD) mice, repeated administration of peptide fragments of target antigens in incomplete Freund's adjuvant has resulted in severe anaphylactic reactions. Although these methods of administration are known to potentiate CD4 T helper 2 (Th2) responses, which is the goal of specific antigen vaccination, the risk of anaphylaxis raises a red flag concerning use of this therapy for diseases such as type I diabetes, where the survival time after onset is quite long. It is clear that specific antigen vaccination is effective in preventing several animal models of autoimmune disease, and in treating these diseases once the symptoms are overt. However, the risks of this therapy require serious consideration of alternative methods for down-regulation of the autoimmune process.
通过在水溶液中给予靶抗原进行特异性抗原疫苗接种,已使实验性变应性脑脊髓炎、I型糖尿病以及几种抗原诱导性关节炎动物模型中的疾病严重程度显著降低,即便在症状出现后给予疫苗接种也是如此。然而,在非肥胖糖尿病(NOD)小鼠的实验性自身免疫性脑脊髓炎(EAE)和I型糖尿病模型中,在不完全弗氏佐剂中重复给予靶抗原的肽片段会导致严重的过敏反应。尽管已知这些给药方法可增强CD4辅助性T细胞2(Th2)反应,而这正是特异性抗原疫苗接种的目标,但过敏反应风险为将该疗法用于I型糖尿病等疾病敲响了警钟,因为I型糖尿病发病后的存活时间相当长。显然,特异性抗原疫苗接种在预防多种自身免疫性疾病动物模型方面有效,且在症状明显后治疗这些疾病时也有效。然而,该疗法的风险需要认真考虑下调自身免疫过程的替代方法。