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用于预防和治疗过敏的DNA疫苗。

DNA vaccines for the prevention and treatment of allergy.

作者信息

Chua Kaw Yan, Kuo I-Chun, Huang Chiung-Hui

机构信息

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

出版信息

Curr Opin Allergy Clin Immunol. 2009 Feb;9(1):50-4. doi: 10.1097/ACI.0b013e3283207ad8.

Abstract

PURPOSE OF REVIEW

Antiallergy DNA vaccine is an attractive alternative for the prevention and treatment of allergic diseases. This review covers recent studies to enhance potency and safety of antiallergy DNA vaccines.

RECENT FINDINGS

Dendritic cell-targeted allergen gene vaccination using fascin gene promoter inhibited IgE production and allergic inflammation but not airway hyperresponsiveness. Targeting allergen expression at immature dendritic cells or induction of tolerogenic dendritic cells could induce antiallergic T regulatory cells. Vaccination with DNA-encoded Ag85B and AIMP1 as adjuvants could downregulate established Th2-mediated allergic responses. Forced ubiquitation or targeting allergens to lysosomal/endosomal compartments could avoid risk of allergen sensitization. Gene gun delivery of conventional antiallergy DNA vaccine is a risk factor. Replicase-based allergy DNA vaccines showed enhanced immunogenecity and safety as compared to conventional DNA vaccines. TANK-binding kinase-1 (TBK1) is a novel key molecule in DNA vaccine-induced immunogenicity.

SUMMARY

Dendritic cell-based approach has been actively explored to enhance immunogenicity of antiallergy DNA vaccines. Codelivery of hypoallergenic DNA vaccines with potent adjuvants via a desirable delivery mode will help to fulfill the requirements for clinical application of antiallergy DNA vaccines. Activation of TBK1 signaling pathway could be a novel strategy to enhance immunogenicity of DNA vaccines.

摘要

综述目的

抗过敏DNA疫苗是预防和治疗过敏性疾病的一种有吸引力的替代方法。本综述涵盖了近期关于提高抗过敏DNA疫苗效力和安全性的研究。

最新发现

使用肌动蛋白结合蛋白基因启动子进行树突状细胞靶向过敏原基因疫苗接种可抑制IgE产生和过敏性炎症,但不能抑制气道高反应性。将过敏原表达靶向未成熟树突状细胞或诱导耐受性树突状细胞可诱导抗过敏调节性T细胞。用DNA编码的Ag85B和AIMP1作为佐剂进行疫苗接种可下调已建立的Th2介导的过敏反应。强制泛素化或将过敏原靶向溶酶体/内体区室可避免过敏原致敏风险。传统抗过敏DNA疫苗的基因枪递送是一个危险因素。与传统DNA疫苗相比,基于复制酶的过敏DNA疫苗显示出增强的免疫原性和安全性。TANK结合激酶-1(TBK1)是DNA疫苗诱导免疫原性中的一种新型关键分子。

总结

基于树突状细胞的方法已被积极探索以增强抗过敏DNA疫苗的免疫原性。通过理想的递送方式将低过敏性DNA疫苗与强效佐剂共递送将有助于满足抗过敏DNA疫苗临床应用的要求。激活TBK1信号通路可能是增强DNA疫苗免疫原性的一种新策略。

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