Sudowe S, Montermann E, Steitz J, Tüting T, Knop J, Reske-Kunz A B
Clinical Research Unit Allergology, Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany.
Gene Ther. 2002 Jan;9(2):147-56. doi: 10.1038/sj.gt.3301625.
DNA-based immunization represents an attractive alternative approach to the current treatment of allergic diseases by specific immunotherapy with allergen extracts. In this study, we used a replication-deficient adenovirus vector (AdCMV), to examine the in vivo efficacy of preventive and therapeutic genetic immunization in a mouse model of type I allergy. Primary immunization with a recombinant adenovirus expressing the model antigen beta-galactosidase (AdCMV-(beta)gal) induced a Th1 immune response (predominance of IgG2a antibodies, high frequency of IFN-gamma producing T cells) and large numbers of cytotoxic T lymphocytes. Prophylactic vaccination with AdCMV-(beta)gal abolished the production of specific IgE following subsequent immunization with (beta)gal-protein, and skewed the Th2-biased immune response to a Th1-orientated response. In contrast, therapeutic administration of AdCMV-(beta)gal after priming with (beta)gal-protein neither significantly inhibited ongoing IgE production nor modulated a manifest Th2 immune response. Thus, allergen gene transfer via recombinant adenovirus represents an effective method to establish protection against the development of allergic disorders, but does not qualify as a therapeutic tool to interfere with ongoing high IgE production.
基于DNA的免疫疗法是目前通过变应原提取物进行特异性免疫疗法治疗变应性疾病的一种有吸引力的替代方法。在本研究中，我们使用复制缺陷型腺病毒载体（AdCMV），在I型过敏小鼠模型中研究预防性和治疗性基因免疫的体内疗效。用表达模型抗原β-半乳糖苷酶的重组腺病毒（AdCMV-βgal）进行初次免疫可诱导Th1免疫反应（IgG2a抗体占优势，产生IFN-γ的T细胞频率高）和大量细胞毒性T淋巴细胞。用AdCMV-βgal进行预防性疫苗接种可消除随后用βgal-蛋白免疫后特异性IgE的产生，并使偏向Th2的免疫反应向Th1方向转变。相反，在用βgal-蛋白致敏后给予AdCMV-βgal进行治疗，既不能显著抑制正在进行的IgE产生，也不能调节明显的Th2免疫反应。因此，通过重组腺病毒进行变应原基因转移是建立针对变应性疾病发展的保护的有效方法，但不能作为干扰正在进行的高IgE产生的治疗工具。
