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首页> 外文期刊>Allergy >Inhibition of type I allergic responses with nanogram doses of replicon-based DNA vaccines.
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Inhibition of type I allergic responses with nanogram doses of replicon-based DNA vaccines.

机译：纳克剂量的基于复制子的DNA疫苗可抑制I型过敏反应。

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Background: Allergic diseases have become a major public health problem in developed countries; yet, no reliable, safe and consistently effective treatment is available. DNA immunization has been shown to prevent and balance established allergic responses, however, the high dose of conventional DNA vaccines necessary for the induction of anti-allergic reactions and their poor immunogenicity in primates require the development of new allergy DNA vaccines. We evaluated protective and therapeutic effects of a Semliki-Forest Virus replicase-based vs a conventional DNA vaccine in BALB/c mice using the model allergen beta-galactosidase. Methods: Immunoglobulin (Ig)E suppression was determined by a basophil release assay as an in vitro correlate for allergen-specific crosslinking capacity of IgE reflecting the in vivo situation in an allergic individual. Th1 memory responses were measured by cytokine detection via enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT). Results:Nanogram amounts of a replicase-based vector triggered a Th1 response comparable with that achieved with the injection of 20 000-times more copies of a conventional DNA plasmid, and induced IgE suppression in both a protective and a therapeutic setting. Conclusions: Replicase-based DNA vaccines fulfill the stringent criteria for an allergy DNA vaccine, i.e. low dose, strong Th1 immunogenicity and memory, lack of 'therapy-induced' IgE production and anaphylactic side effects. Moreover, by triggering apoptosis in transfected cells, their unique 'immunize and disappear' feature minimizes the hypothetical risks of genomic integration or induction of autoimmunity.
机译：背景：过敏性疾病已成为发达国家的主要公共卫生问题。但是，尚无可靠，安全且持续有效的治疗方法。 DNA免疫已显示可预防和平衡已确立的过敏反应，但是，诱导抗过敏反应所需的高剂量常规DNA疫苗及其在灵长类动物中的不良免疫原性需要开发新的过敏DNA疫苗。我们使用模型变应原β-半乳糖苷酶评估了基于Semliki-Forest Virus复制酶的疫苗与常规DNA疫苗在BALB / c小鼠中的保护和治疗效果。方法：通过嗜碱性粒细胞释放测定确定免疫球蛋白（Ig）E的抑制作用，这是IgE过敏原特异性交联能力的体外相关指标，反映了过敏个体的体内情况。通过酶联免疫吸附测定（ELISA）和酶联免疫斑点测定（ELISPOT）通过细胞因子检测来测量Th1记忆反应。结果：纳米量的基于复制酶的载体引发的Th1反应与注射传统DNA质粒2万倍以上所获得的Th1反应相当，并在保护性和治疗性环境中均诱导了IgE抑制。结论：基于复制酶的DNA疫苗符合过敏性DNA疫苗的严格标准，即低剂量，强大的Th1免疫原性和记忆力，缺乏“治疗诱导”的IgE产生和过敏性副作用。此外，通过触发转染细胞的凋亡，其独特的“免疫消失”功能将基因组整合或自身免疫诱导的假设风险降至最低。

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