HuangFu TaoQi, Lim Lay Hong, Chua Kaw Yan
Department of Paediatrics, Faculty of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Republic of Singapore.
Vaccine. 2006 May 22;24(21):4576-81. doi: 10.1016/j.vaccine.2005.08.028. Epub 2005 Aug 22.
Der p 1 is a major allergen that reacts with IgE in more than 70% allergic sera, hence a good candidate for DNA vaccine development. Previous study demonstrated that intramuscular injection of plasmid DNA containing wild type Der p 1 gene induced specific Th1 skewed immune response. The aim of this study is to further optimize the DNA construct to achieve preventive and therapeutic efficacies. An optimized construct, containing mouse Igkappa light chain leader sequence followed by codon optimized mature Der p 1 gene, was generated and used to prevent or treat Der p1 induced allergic asthma in an experimental model. Results showed that this optimized construct was effective in the inhibition of Der p 1 specific IgE levels, attenuation of Th2 response and reduction of airway hyperresponsiveness in terms of prophylactic efficacy. It also showed therapeutic efficacy in IgE inhibition and up-regulation of IgG2a and IFN-gamma. The information obtained here could facilitate the design of DNA vaccines for allergy in general.
Der p 1是一种主要过敏原,能与70%以上过敏性血清中的IgE发生反应,因此是DNA疫苗开发的理想候选物。先前的研究表明,肌肉注射含有野生型Der p 1基因的质粒DNA可诱导特异性Th1偏向性免疫反应。本研究的目的是进一步优化DNA构建体,以实现预防和治疗效果。构建了一种优化的构建体,其包含小鼠Igkappa轻链前导序列,随后是密码子优化的成熟Der p 1基因,并用于在实验模型中预防或治疗Der p1诱导的过敏性哮喘。结果表明,就预防效果而言,这种优化的构建体在抑制Der p 1特异性IgE水平、减弱Th2反应和降低气道高反应性方面是有效的。它在IgE抑制以及IgG2a和IFN-γ的上调方面也显示出治疗效果。此处获得的信息总体上有助于设计用于过敏的DNA疫苗。