Ludwig-Portugall Isis, Montermann Evelyn, Kremer Andrea, Reske-Kunz Angelika B, Sudowe Stephan
Clinical Research Unit of Allergology, Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany.
J Allergy Clin Immunol. 2004 Oct;114(4):951-7. doi: 10.1016/j.jaci.2004.06.013.
Vaccination with allergen-encoding DNA represents a promising approach for the treatment of allergic diseases.
In a mouse model of type I allergy, we analyzed the ability of biolistic transfection to inhibit antigen-specific IgE production and to modulate TH2 responses.
BALB/c mice were vaccinated by means of gene gun-mediated DNA immunization with plasmid vector pCMV-betaGal, encoding beta-galactosidase as a model allergen. Subsequently, mice were immunized by means of repeated intraperitoneal injection of beta-galactosidase adsorbed to the adjuvant aluminum hydroxide. Development of IgE, IgG1, and IgG2a antibody titers during the course of immunization was followed, and anaphylactic potential of sera was determined by using RBL-2H3 degranulation assay. Spleen cells of vaccinated mice and unvaccinated control animals were stimulated in vitro to analyze cytokine production and induction of CD8 + effector T cells.
Gene gun-mediated DNA immunization with pCMV-betaGal very efficiently prevented IgE antibody production on a long-term basis. Concomitantly, IgG1 antibody levels in vaccinated mice were strongly reduced, whereas IgG2a antibody production was increased. Analysis of cytokine profiles indicated immune deviation from a TH2-biased response in control mice toward a mixed TH1/TH2 response in vaccinated mice. In addition, substantial numbers of IFN-gamma-producing CD8 + effector T cells were found in vaccinated mice.
Gene gun-mediated DNA vaccination prevents the induction of long-lasting IgE antibody production.
用编码变应原的DNA进行疫苗接种是治疗变应性疾病的一种有前景的方法。
在I型变态反应小鼠模型中，我们分析了生物弹道转染抑制抗原特异性IgE产生及调节TH2反应的能力。
用基因枪介导的DNA免疫法，以编码β-半乳糖苷酶作为模型变应原的质粒载体pCMV-βGal对BALB/c小鼠进行疫苗接种。随后，通过反复腹腔注射吸附于佐剂氢氧化铝的β-半乳糖苷酶对小鼠进行免疫。在免疫过程中跟踪IgE、IgG1和IgG2a抗体滴度的变化，并通过RBL-2H3脱颗粒试验测定血清的过敏反应潜能。体外刺激接种疫苗小鼠和未接种疫苗对照动物的脾细胞，以分析细胞因子的产生及CD8+效应T细胞的诱导情况。
用pCMV-βGal进行基因枪介导的DNA免疫能非常有效地长期预防IgE抗体的产生。同时，接种疫苗小鼠的IgG1抗体水平大幅降低，而IgG2a抗体产生增加。细胞因子谱分析表明，免疫反应从对照小鼠偏向TH2的反应转变为接种疫苗小鼠的混合TH1/TH2反应。此外，在接种疫苗的小鼠中发现了大量产生IFN-γ的CD8+效应T细胞。
基因枪介导的DNA疫苗接种可预防持久的IgE抗体产生。
